Five-year longitudinal changes in quantitative spinal cord MRI in multiple sclerosis.

BACKGROUND: The spinal cord (SC) is highly relevant to disability in multiple sclerosis (MS), but few studies have evaluated longitudinal changes in quantitative spinal cord magnetic resonance imaging (SC-MRI). OBJECTIVES: The aim of this study was to characterize the relationships between 5-year changes in SC-MRI with disability in MS. METHODS: In total, 75 MS patients underwent 3 T SC-MRI and clinical assessment (expanded disability status scale (EDSS) and MS functional composite (MSFC)) at baseline, 2 and 5 years. SC-cross-sectional area (CSA) and diffusion-tensor indices (fractional anisotropy (FA), mean, perpendicular, parallel diffusivity (MD, λ⊥, λ||) and magnetization transfer ratio (MTR)) were extracted at C3-C4. Mixed-effects regression incorporating subject-specific slopes assessed longitudinal change in SC-MRI measures. RESULTS: SC-CSA and MTR decreased (p = 0.009, p = 0.03) over 5.1 years. There were moderate correlations between 2- and 5-year subject-specific slopes of SC-MRI indices and follow-up EDSS scores (Pearson's r with FA = -0.23 (p < 0.001); MD = 0.31 (p < 0.001); λ⊥ = 0.34 (p < 0.001); λ|| = -0.12 (p = 0.05), MTR = -0.37 (p < 0.001); SC-CSA = -0.47 (p < 0.001) at 5 years); MSFC showed similar trends. The 2- and 5-year subject-specific slopes were robustly correlated (r = 0.93-0.97 for FA, λ⊥, SC-CSA and MTR, all ps < 0.001). CONCLUSION: In MS, certain quantitative SC-MRI indices change over 5 years, reflecting ongoing tissue changes. Subject-specific trajectories of SC-MRI index change at 2 and 5 years are strongly correlated and highly relevant to follow-up disability. These findings suggest that individual dynamics of change should be accounted for when interpreting longitudinal SC-MRI measures and that measuring short-term change is predictive of long-term clinical disability.

Personal protective equipment use during industrial hog operation work activities and acute lung function changes in a prospective worker cohort, North Carolina 2014-2015.

INTRODUCTION: Occupational activities related to industrial hog operation (IHO) worker lung function are not well defined. Therefore, we aimed to identify IHO work activities associated with diminished respiratory function and the effectiveness, if any, of personal protective equipment (PPE) use on IHOs. METHODS: From 2014 to 2015, 103 IHO workers were enrolled and followed for 16 weeks. At each biweekly visit, work activities and PPE use were self-reported via questionnaire and lung function measurements were collected via spirometry. Generalized linear and linear fixed-effects models were fitted to cross-sectional and longitudinal data. RESULTS: Increasing years worked on an IHO were associated with diminished lung function, but baseline and longitudinal work activities were largely inconsistent in direction and magnitude. Unexpectedly, a -0.3 L (95% confidence interval: -0.6, -0.04) difference in forced expiratory volume in the first second (FEV1 ) was estimated when workers wore PPE consistently (≥80% of the time at work) versus those weeks they did not. In post-hoc analyses, we found that coveralls and facemasks were worn less consistently when workers experienced worse barn conditions and had more contact with pigs, but coveralls were worn more consistently as cleaning activities increased. CONCLUSIONS: Similar to past studies, baseline estimates were likely obscured by healthy worker effect bias, but showed decrements in worker lung function as years of work increased. A challenge to disentangling the effect of work activities on lung function was the discovery that IHO workers used PPE differently according to the work task. These data suggest that interventions may be targeted toward improving barn conditions so that workers can consistently utilize IHO-provided PPE.

Self-reported work activities, eye, nose, and throat symptoms, and respiratory health outcomes among an industrial hog operation worker cohort, North Carolina, USA.

INTRODUCTION: Respiratory disease among industrial hog operation (IHO) workers is well documented; however, it remains unclear whether specific work activities are more harmful and if personal protective equipment (PPE), as used by workers, can reduce adverse health outcomes. METHODS: IHO workers (n = 103) completed baseline and up to eight bi-weekly study visits. Workers reported typical (baseline) and transient (bi-weekly) work activities, PPE use, and physical health symptoms. Baseline and longitudinal associations were assessed using generalized logistic and fixed-effects logistic regression models, respectively. RESULTS: At baseline, reports of ever versus never drawing pig blood, applying pesticides, and increasing years worked at any IHO were positively associated with reports of eye, nose, and/or throat irritation. Over time, transient exposures, associated with dustiness in barns, cleaning of barns, and pig contact were associated with increased odds of sneezing, headache, and eye or nose irritation, particularly in the highest categories of exposure. When PPE was used, workers had lower odds of symptoms interfering with sleep (odds ratio [OR]: 0.1; 95% confidence interval [CI]: 0.01-0.8), and eye or nose irritation (OR: 0.1; 95% CI: 0.02-0.9). Similarly, when they washed their hands eight times or more per shift (median frequency) versus less frequently, the odds of any respiratory symptom were reduced (OR: 0.3; 95% CI: 0.1-0.8). CONCLUSIONS: In this healthy volunteer worker population, increasingly unfavorable IHO activities were associated with self-reported eye, nose, throat, and respiratory health symptoms. Strong protective associations were seen between PPE use and handwashing and the odds of symptoms, warranting further investigation.

Intrahost Dynamics of Human Cytomegalovirus Variants Acquired by Seronegative Glycoprotein B Vaccinees.

Human cytomegalovirus (HCMV) is the most common congenital infection worldwide and a frequent cause of hearing loss and debilitating neurologic disease in newborn infants. Thus, a vaccine to prevent HCMV-associated congenital disease is a public health priority. One potential strategy is vaccination of women of child bearing age to prevent maternal HCMV acquisition during pregnancy. The glycoprotein B (gB) plus MF59 adjuvant subunit vaccine is the most efficacious tested clinically to date, demonstrating 50% protection against primary HCMV infection in a phase 2 clinical trial. Yet, the impact of gB/MF59-elicited immune responses on the population of viruses acquired by trial participants has not been assessed. In this analysis, we employed quantitative PCR as well as multiple sequencing methodologies to interrogate the magnitude and genetic composition of HCMV populations infecting gB/MF59 vaccinees and placebo recipients. We identified several differences between the viral dynamics in acutely infected vaccinees and placebo recipients. First, viral load was reduced in the saliva of gB vaccinees, though not in whole blood, vaginal fluid, or urine. Additionally, we observed possible anatomic compartmentalization of gB variants in the majority of vaccinees compared to only a single placebo recipient. Finally, we observed reduced acquisition of genetically related gB1, gB2, and gB4 genotype "supergroup" HCMV variants among vaccine recipients, suggesting that the gB1 genotype vaccine construct may have elicited partial protection against HCMV viruses with antigenically similar gB sequences. These findings suggest that gB immunization had a measurable impact on viral intrahost population dynamics and support future analysis of a larger cohort.IMPORTANCE Though not a household name like Zika virus, human cytomegalovirus (HCMV) causes permanent neurologic disability in one newborn child every hour in the United States, which is more than that for Down syndrome, fetal alcohol syndrome, and neural tube defects combined. There are currently no established effective measures to prevent viral transmission to the infant following HCMV infection of a pregnant mother. However, the glycoprotein B (gB)/MF59 vaccine, which aims to prevent pregnant women from acquiring HCMV, is the most successful HCMV vaccine tested clinically to date. Here, we used viral DNA isolated from patients enrolled in a gB vaccine trial who acquired HCMV and identified several impacts that this vaccine had on the size, distribution, and composition of the in vivo viral population. These results have increased our understanding of why the gB/MF59 vaccine was partially efficacious, and such investigations will inform future rational design of a vaccine to prevent congenital HCMV.

Interventions Made to Preserve Cognitive Function Trial (IMPCT) study protocol: a multi-dialysis center 2x2 factorial randomized controlled trial of intradialytic cognitive and exercise training to preserve cognitive function.

BACKGROUND: Kidney disease and dialysis significantly impact cognitive function across the age spectrum. Cognitive training (CT) and/or exercise training (ET) are promising approaches to preserve cognitive function among community-dwelling older adults, but have not been tested for cognition preservation in hemodialysis patients of all ages. In this manuscript, we summarize the protocol for the Interventions Made to Preserve Cognitive Function Trial (IMPCT). METHODS: We will perform a 2 × 2 factorial randomized controlled trial (RCT) of eligible adult (≥18 years) hemodialysis initiates (n = 200) to test whether intradialytic CT (brain games on a tablet PC), ET (foot peddlers) and combined CT + ET while undergoing hemodialysis preserves executive function compared to standard of care (SC). Participants will engage in the interventions to which they are randomized for 6 months. The primary objective is to compare, among interventions, the 3-month change in executive function measured using the Trail Making Test A (TMTA) and B (TMTB); specifically, executive function is calculated as TMTB-TMTA to account for psychomotor speed. This primary outcome was selected based on findings from our pilot study. The secondary objectives are to compare the risk of secondary cognitive outcomes, ESKD-specific clinical outcomes, and patient-centered outcomes at 3-months and 6-months. All data collection and interventions are conducted in the dialysis center. DISCUSSION: We hypothesize that receiving intradialytic CT or ET will better preserve executive function than SC but receiving combined CT + ET, will be the most effective intervention. The current trial will be an important step in understanding how intradialytic interventions might preserve cognitive health. TRIAL REGISTRATION: Clinicaltrials.Gov (Date: 8/6/18): # NCT03616535 . Protocol Version: 10 (April 2020). FUNDING: NIDDK R01DK114074.

Adaptation and validation of UNICEF/Washington group child functioning module at the Iganga-Mayuge health and demographic surveillance site in Uganda.

BACKGROUND: The UNICEF/Washington Group Child Functioning Module (CFM) assesses child functioning among children between 5 and 17 years of age. This study adapted and validated the CFM at the Iganga-Mayuge Health and Demographic Surveillance Site (IM-HDSS) in Uganda. METHODS: This cross-sectional study was conducted between September 2018-January 2019 at the IM-HDSS. Respondents were caregivers of children between 5 and 17 years of age who were administered modified Washington Group short set (mWG-SS) and CFM. The responses were recorded on a 4-point Likert scale. Descriptive analysis was conducted on child and caregiver demographic characteristics. Exploratory factor analysis (EFA) assessed underlying factor structure, dimensionality and factor loadings. Cronbach's alpha was reported as an assessment of internal consistency. Face validity was assessed during the translation process, and concurrent validity of CFM was assessed through comparison with disability short form. RESULTS: Out of 1842 caregivers approached, 1439 (78.1%) participated in the study. Mean age of children was 11.06 ± 3.59 years, 51.4% were males, and 86.1% had a primary caregiver. Based on EFA, vision, hearing, walking, self-care, communication, learning, remembering, concentrating, accepting change, behavior control, and making friends loaded on factor 1 - "Motor and Cognition," while anxiety and depression loaded on factor 2 - "Mood". Cronbach's alpha for the overall CFM was 0.899 (good internal consistency). Cronbach's alpha for each extracted factor was excellent, motor and cognition (0.904), and mood (0.902). CFM had acceptable face validity. Spearman's rank correlation between scores of CFM and modified WG short set was 0.51 (p-value < 0.001). The overall mean CFM score was 2.47 ± 3.82 out of 39. The mean score for Mood (1.35 ± 1.42 out of 6) was higher compared to Motor and Cognition (1.12 ± 3.06 out of 33). Comparing modified WG short set and CFM Likert responses, the percent agreement was greatest for "cannot do at all." CONCLUSION: CFM is a two-factor, valid and reliable scale for assessing disability in Uganda and can be applied to other similar settings to contribute towards disability data from the region. It is an easy-to-administer tool that can help in deeper understanding of context-specific burden and extent of disability in children between 5 and 17 years of age.

Thrombolytic removal of intraventricular haemorrhage in treatment of severe stroke: results of the randomised, multicentre, multiregion, placebo-controlled CLEAR III trial.

BACKGROUND: Intraventricular haemorrhage is a subtype of intracerebral haemorrhage, with 50% mortality and serious disability for survivors. We aimed to test whether attempting to remove intraventricular haemorrhage with alteplase versus saline irrigation improved functional outcome. METHODS: In this randomised, double-blinded, placebo-controlled, multiregional trial (CLEAR III), participants with a routinely placed extraventricular drain, in the intensive care unit with stable, non-traumatic intracerebral haemorrhage volume less than 30 mL, intraventricular haemorrhage obstructing the 3rd or 4th ventricles, and no underlying pathology were adaptively randomly assigned (1:1), via a web-based system to receive up to 12 doses, 8 h apart of 1 mg of alteplase or 0·9% saline via the extraventricular drain. The treating physician, clinical research staff, and participants were masked to treatment assignment. CT scans were obtained every 24 h throughout dosing. The primary efficacy outcome was good functional outcome, defined as a modified Rankin Scale score (mRS) of 3 or less at 180 days per central adjudication by blinded evaluators. This study is registered with ClinicalTrials.gov, NCT00784134. FINDINGS: Between Sept 18, 2009, and Jan 13, 2015, 500 patients were randomised: 249 to the alteplase group and 251 to the saline group. 180-day follow-up data were available for analysis from 246 of 249 participants in the alteplase group and 245 of 251 participants in the placebo group. The primary efficacy outcome was similar in each group (good outcome in alteplase group 48% vs saline 45%; risk ratio [RR] 1·06 [95% CI 0·88-1·28; p=0·554]). A difference of 3·5% (RR 1·08 [95% CI 0·90-1·29], p=0·420) was found after adjustment for intraventricular haemorrhage size and thalamic intracerebral haemorrhage. At 180 days, the treatment group had lower case fatality (46 [18%] vs saline 73 [29%], hazard ratio 0·60 [95% CI 0·41-0·86], p=0·006), but a greater proportion with mRS 5 (42 [17%] vs 21 [9%]; RR 1·99 [95% CI 1·22-3·26], p=0·007). Ventriculitis (17 [7%] alteplase vs 31 [12%] saline; RR 0·55 [95% CI 0·31-0·97], p=0·048) and serious adverse events (114 [46%] alteplase vs 151 [60%] saline; RR 0·76 [95% CI 0·64-0·90], p=0·002) were less frequent with alteplase treatment. Symptomatic bleeding (six [2%] in the alteplase group vs five [2%] in the saline group; RR 1·21 [95% CI 0·37-3·91], p=0·771) was similar. INTERPRETATION: In patients with intraventricular haemorrhage and a routine extraventricular drain, irrigation with alteplase did not substantially improve functional outcomes at the mRS 3 cutoff compared with irrigation with saline. Protocol-based use of alteplase with extraventricular drain seems safe. Future investigation is needed to determine whether a greater frequency of complete intraventricular haemorrhage removal via alteplase produces gains in functional status. FUNDING: National Institute of Neurological Disorders and Stroke.

Cytomegalovirus Kinetics Following Primary Infection in Healthy Women.

The kinetics of cytomegalovirus (CMV) DNA in infected asymptomatic hosts are largely unknown. We measured viral load (VL) in 124 fluid samples (oral, urine, vaginal, blood) collected from 21 women who acquired CMV. A quantitative real-time polymerase chain reaction assay of US17, which correlated with clinical assays, was used. VL decreased following primary infection in all fluids. The geometric mean VL of vaginal fluid was significantly higher than that of other sources: oral (3.89; 95% confidence interval [CI], 1.43-10.57), urine (6.36; 95% CI, 2.48-16.32), and whole blood (11.88; 95% CI, 4.12-34.20). Vaginal CMV shedding may provide a route for sexual and possibly perinatal transmission.

Survival after Breast-Conserving Surgery with Whole Breast or Partial Breast Irradiation in Women with Early Stage Breast Cancer: A SEER Data-base Analysis.

Randomized clinical trials have demonstrated equivalency in survival outcomes for early stage breast cancer patients treated with either mastectomy or breast-conserving surgery (BCS) with radiation. Recent, state-level data confirm comparable survival outcomes. Using Surveillance Epidemiology and End Research (SEER) data, we sought to evaluate survival outcomes among patients with early stage breast cancer treated with mastectomy, BCS with whole breast irradiation (BCS + WBI), or BCS with accelerated partial breast irradiation (BCS + APBI). Data on women 50 years or older diagnosed with a node negative invasive breast cancer (≤3 cm in size) between 1995 and 2009 were extracted from the SEER data base. Women treated with mastectomy alone or BCS with radiation were eligible for analysis. Kaplan-Meier estimates and Cox proportional hazard models were used to compare overall survival (OS) and cancer-specific survival (CSS) among the treatment groups. 150,171 women fulfilled inclusion criteria. OS was significantly improved among women treated with BCS and WBI or BCS and APBI compared to mastectomy alone. Adjusted hazard ratios for death in BCS with WBI or APBI (versus mastectomy alone) were 0.73 (95% CI: 0.71, 0.76) and 0.68 (95% CI: 0.58, 0.79), respectively. Adjusted CSS was also significantly improved in patients treated with BCS and WBI (HR 0.80, 95% CI: 0.76, 0.85) as compared to mastectomy. BCS with radiation (WBI or APBI) was associated with significantly improved OS and CSS, versus mastectomy alone. These results support the use of BCS with WBI or APBI (in well selected patients) for the treatment of breast cancer.

Elevated blood pressure in adolescent girls: correlation to body size and composition.

BACKGROUND: To improve understanding of the pathophysiology of hypertension in adolescents and pave the way for risk stratification, studies have sought to determine the correlates of blood pressure (BP). Inconsistencies in dependent and independent variables have resulted in an elusive consensus. The aim of this report is to examine an inclusive array of correlates of BP, as a continuous (systolic and diastolic BP) and a dichotomous variable. METHODS: Subjects were a school-based sample of 730 urban, mostly African American, non-referred 6th and 7th grade girls. To find independent correlates of SBP/DBP, we used a stepwise model selection method based on the Schwarz Bayesian Information Criterion, enabling selection of a parsimonious model among highly correlated covariates. Candidate variables were: age, stature, heart rate, pubertal development, BMI, BMI z-score, waist circumference, waist-to-height ratio (WHtR), body surface area, fat mass (by bioelectrical impedance analysis), fat-free mass (FFM), percentage of body fat, and presence of overweight/obesity. RESULTS: The best-fitting models for DBP and SBP (considered separately) included fat-free mass, heart rate and, in the case of SBP, stature. The best-fitting model for high-normal/elevated blood pressure (H-N/EBP) included WHtR with no independent relation of any other variable. The prevalence of H-N/EBP tripled between a WHtR of 0.5 and 0.7. CONCLUSIONS: The easily obtained and calculated WHtR is the strongest correlate of elevated blood pressure among available variables and is a prime candidate for longitudinal studies of predictors of the development of hypertension. TRIAL REGISTRATION: ClinicalTrials.gov Identifier, NCT00746083.

Comparing the Maryland Comprehensive Cancer Control Plan With Federal Cancer Prevention and Control Recommendations.

INTRODUCTION: Since the introduction of the Affordable Care Act (ACA) in 2012, 11 million more Americans now have access to preventive services via health care coverage. Several prevention-related recommendations issued by the US Preventive Services Task Force (USPSTF), Centers for Disease Control and Prevention (CDC), and Advisory Committee on Immunization Practices (ACIP) are covered under the ACA. State cancer plans often provide prevention strategies, but whether these strategies correspond to federal evidence-based recommendations is unclear. The objective of this article is to assess whether federal evidence-based recommendations, including those covered under the ACA, are included in the Maryland Comprehensive Cancer Control Plan (MCCCP). METHODS: A total of 19 federal recommendations pertaining to cancer prevention and control were identified. Inclusion of federal cancer-related recommendations by USPSTF, CDC, and ACIP in the MCCCP's goals, objectives, and strategies was examined. RESULTS: Nine of the federal recommendations were issued after the MCCCP's publication. MCCCP recommendations corresponded completely with 4 federal recommendations and corresponded only partially with 3. Reasons for partial correspondence included specification of less restrictive at-risk populations or different intervention implementers. Three federal recommendations were not mentioned in the MCCCP's goals, objectives, and strategies. CONCLUSION: Many cancer-related federal recommendations were released after the MCCCP's publication and therefore do not appear in the most current version. We recommend that the results of this analysis be considered in the update of the MCCCP. Our findings underscore the need for a periodic scan for changes to federal recommendations and for adjusting state policies and programs to correspond with federal recommendations, as appropriate for Marylanders.

Short versus prolonged courses of antibiotic therapy for children with uncomplicated Gram-negative bacteraemia.

OBJECTIVES: The optimal duration of antibiotic therapy for uncomplicated Gram-negative bacteraemia remains undefined. Our objective was to compare clinical outcomes of receiving short (7-10 days) versus prolonged (>10 days) durations of antibiotic therapy for children with uncomplicated Gram-negative bacteraemia. METHODS: We conducted a retrospective cohort study of children with uncomplicated Gram-negative bacteraemia at The Johns Hopkins Hospital between 2002 and 2012. We estimated the risk of bacteraemic relapse among children who received short versus prolonged durations of antibiotic therapy using 1:1 nearest neighbour propensity score matching without replacement prior to performing regression analysis. RESULTS: There were 170 matched pairs that were well balanced on baseline covariates. The median duration of therapy in the short and prolonged courses was 10 days (IQR 10-10) and 14 days (IQR 14-17), respectively. The 30 day mortality was similar between the groups (OR 1.12; 95% CI 0.96-1.21). A prolonged duration of antibiotic therapy did not reduce the relapse risk compared with shorter durations (adjusted hazard ratio 0.67; 95% CI 0.35-1.27). Similarly, each additional day of antibiotic therapy was not protective against relapse risk (adjusted hazard ratio 0.99 per additional day; 95% CI 0.92-1.03). There was a trend towards an increased subsequent risk of candidaemia in children receiving longer treatment durations (hazard ratio 2.44; 95% CI 0.97-6.19). CONCLUSIONS: Antibiotic treatment for more than 10 days for uncomplicated bacteraemia in children does not reduce the risk of microbiological relapse compared with shorter-course therapy, but may be associated with an increased risk of candidaemia. Our findings need to be confirmed in a larger, prospective study.

Perceived discrimination, patient trust, and adherence to medical recommendations among persons with sickle cell disease.

BACKGROUND: Adults with sickle cell disease (SCD) report experiencing discriminatory behavior from some healthcare providers. The impact of discrimination on health outcomes in SCD, including adherence to physician recommendations, is not known. OBJECTIVE: Our aim was to evaluate the association between perceived discrimination from healthcare providers and nonadherence to physician recommendations among persons with SCD, and to test the potentially mediating role of patient trust. PARTICIPANTS: Patients with SCD (age 15 years and older) participating in the Improving Patient Outcomes with Respect and Trust (IMPORT) Study. MAIN MEASURES: Perceived discrimination from healthcare providers and reported adherence to physician recommendations were assessed by patient self-report using items from the 2001 Commonwealth Fund Health Survey. Interpersonal trust in medical professionals was assessed using the short form of the Wake Forest Trust in Medical Professionals instrument. DESIGN: We used a cross-sectional analysis of IMPORT participant data. Multivariable Poisson regression models were used to test the independent association of discrimination with adherence and to test patient trust as a potential mediator. KEY RESULTS: Among 273 SCD patients with complete data on all variables of interest, patients reporting experiences of discrimination in the healthcare system were 53% more likely to also report being nonadherent to physician recommendations. Trust in medical professionals appeared to mediate the discrimination/nonadherence relationship, accounting for 50% of the excess prevalence of nonadherence among those experiencing discrimination. CONCLUSION: SCD patient perceptions of discriminatory experiences from healthcare providers are associated with greater nonadherence to physician recommendations, and may be a potential factor contributing to disparities in health and health quality among this patient population. Perceived discrimination appears to affect adherence behaviors through the pathway of patient trust. Improving relationships between healthcare providers and SCD patients may improve the trust that SCD patients have in medical professionals, which in turn may improve other outcomes among this underserved patient population.

Attitudes toward clinical trials among patients with sickle cell disease.

Background A substantial number of planned clinical trials for sickle cell disease (SCD) have terminated early due to insufficient patient enrollment. Purpose To describe attitudes toward clinical trials among a sample of adults with SCD and identify patient-level factors associated with these attitudes. Methods Our data came from a sample (N = 291) of primarily adults with SCD participating in the Improving Patient Outcomes with Respect and Trust (IMPORT) study, which is a federally funded observational study of SCD patient experiences in seeking healthcare. Attitudes toward clinical trials were assessed using items from the Perceptions of Participation in Clinical Research instrument. Patient factors examined as potential correlates of clinical trial attitudes were demographics, disease severity, engagement in self-care, trust, healthcare experience ratings, and prior history of participation in clinical trials. Multiple regression analyses were used to identify patient-level correlates of clinical trial attitudes. Results Our sample of SCD patients expressed overwhelmingly favorable attitudes about clinical trials, with 77%-92% of our sample expressing agreement with a series of positive statements about clinical trials in general. Demographics, engagement in self-care, healthcare experience ratings, and prior trial participation each explained significant portions of the variability in clinical trial attitudes. Limitations The generalizability of our results to the entire SCD population may be of concern as the study participants were all receiving care at comprehensive sickle cell centers and already participating in clinical research. Conclusion Our results suggest that, in principle, adults with SCD enrolled in an observational study express very positive general attitudes about clinical trial participation and that specific factors attached to particular clinical trial opportunities may play a greater role in a SCD patient's decision to participate than a general unwillingness to participate.

The Modified Graeb Score: an enhanced tool for intraventricular hemorrhage measurement and prediction of functional outcome.

BACKGROUND AND PURPOSE: Simple and rapid measures of intraventricular hemorrhage (IVH) volume are lacking. We developed and validated a modification of the original Graeb scale to facilitate rapid assessment of IVH over time. METHODS: We explored the relationship between the modified Graeb scale (mGS), original Graeb scale, measured IVH volume, and outcome using data from the Clot Lysis: Evaluating Accelerated Resolution of Hemorrhage with rtPA B (CLEAR B) study. We also explored its reliability. We then evaluated the relationship between mGS and outcome in a large sample of participants with IVH using data contained within the Virtual International Stroke Trials Archive (VISTA). We defined outcome using the modified Rankin scale (>3 signifying poor outcome). RESULTS: The CLEAR B study included 360 scans from 36 subjects. The mGS score and IVH volume were highly correlated (R = 0.80, P<0.0001, R(2) 0.65). Baseline mGS was predictive of poor outcome (area under receiving operating characteristic curve 0.74, 95% confidence interval, 0.57-0.91), whereas the original Graeb scale was not. The VISTA study included 399 participants. Each unit increase in the mGS led to a 12% increase in the odds of a poor outcome (odds ratio, 1.12; 95% confidence interval, 1.05-1.19). Measures of reliability (intra- and inter- reader) were good in both studies. CONCLUSIONS: The mGS, a semiquantitative scale for IVH volume measurement, is a reliable measure with prognostic validity suitable for rapid use in clinical practice and in research.

Multiparametric MRI correlates of sensorimotor function in the spinal cord in multiple sclerosis.

BACKGROUND: Spinal cord (SC) pathology is a major contributor to clinical disability in multiple sclerosis (MS). Conventional magnetic resonance imaging (MRI), specifically SC-MRI lesion load measures that include lesion count and volume, demonstrate only a modest relationship with the clinical status of MS patients. Although SC cross-sectional area (CSA) correlates better with clinical dysfunction than MRI lesion count, SC atrophy likely signifies irreversible tissue loss. Using quantitative MRI indices sensitive to early and late microstructural changes in the spinal cord, we searched for the presence of better correlations between MRI measures and clinical status in MS. OBJECTIVES: We investigated whether diffusion-tensor imaging indices and the magnetization-transfer ratio (MTR) were better associated with the clinical status of MS patients than conventional SC-MRI measures. METHODS: A total of 129 MS patients underwent 3-tesla cervical SC-MRI and quantitative sensorimotor function testing, using the Vibratron-II and dynamometer. Regions-of-interest circumscribed the SC on axial slices between C3-C4. We calculated SC-CSA, fractional anisotropy (FA), mean diffusivity (MD), perpendicular diffusivity (λ perpendicular), parallel diffusivity (λ||) and MTR. We used multivariable linear regression to determine if there were any associations between MRI indices and clinical measures of dysfunction. RESULTS: All MRI indices were significantly different in subjects with MS versus healthy controls, and between the progressive versus relapsing MS subtypes, with the exception of λ||. In multivariable regression models that were adjusted for age, sex, brain parenchymal fraction, and SC-CSA, the MRI indices independently explained variability in hip flexion strength (p-values: MD, λ perpendicular, λ|| < 0.001; FA = 0.07), vibration sensation threshold (p-values: FA = 0.04; MTR = 0.05; λ perpendicular = 0.06), and Expanded Disability Status Scale scores (p-values: FA = 0.003; MD = 0.03; λ perpendicular = 0.005; MTR = 0.02). CONCLUSIONS: In a large, heterogeneous MS sample, quantitative SC-MRI indices demonstrated independent associations with system-specific and global clinical dysfunction. Our findings suggest that the indices studied may provide important information about microstructural SC changes and the substrates of limb disability in MS. The identified structure-function relationships underpin the potential utility of these measures in assessments of therapeutic efficacy.

Are There Differences between the Stress Responses of Philippine Men and Women to the COVID-19 Pandemic?

The SARS-CoV-2 pandemic has had a deleterious impact on human health since its beginning in 2019. The purpose of this study was to examine the psychosocial impact of the COVID-19 pandemic in the Philippines and determine if there were differential impacts on women compared to men. A web-based survey was conducted in the Luzon Islands of the Philippines, during the pandemic quarantine. A total of 1879 participants completed online surveys between 28 March-12 April 2020. A bivariate analysis of both men and women for each psychological measure (stress, anxiety, depression, and impact of COVID-19) was conducted. Multivariable logistic regression models were built for each measure, dichotomized as high or low, separately for men and women. Younger age (p < 0.001), being married (p < 0.001), and being a parent (p < 0.004) were associated with women's poor mental health. Marriage and large household size are protective factors for men (p < 0.002 and p < 0.0012, respectively), but marriage may be a risk factor for women (p < 0.001). Overall, women were disproportionately negatively impacted by the pandemic compared to men.

Discordance between CD4+ T-lymphocyte counts and percentages in HIV-infected persons with liver fibrosis.

BACKGROUND: Cirrhosis of the liver can induce splenic sequestration of peripheral blood cells, recently suggested to reduce the number but not percentage of circulating CD4(+) T cells in persons uninfected with human immunodeficiency virus (HIV). We investigated whether earlier stages of liver fibrosis prior to cirrhosis were associated with discordance between CD4 count (CD4N) and CD4 percentage (CD4%) in HIV-infected patients. METHODS: In cross-sectional analysis of 287 HIV-infected participants of the AIDS Linked to the Intravenous Experience cohort, we evaluated CD4N, CD4%, and transient elastography staging of liver fibrosis. High CD4(+) lymphocyte discordance was defined as higher CD4% relative to CD4N based on accepted clinical cutoffs; multivariable logistic regression was used to determine covariates associated with discordance. RESULTS: Of 287 participants, 99 (34.4%) had high CD4(+) discordance, which increased to 76% of 114 participants with marked lymphopenia (total lymphocyte count [TLC] ≤1200 cells/µL). In multivariable analysis, the odds of having high CD4(+) discordance was increased in persons with significant liver fibrosis compared to those without fibrosis (odds ratio, 1.69; 95% confidence interval [CI], .95-2.96); the odds ratio of discordance increased to 2.66 (95% CI, 1.11-6.40) among the subset of participants with TLC ≤1200 cells/µL. The odds for discordance associated with cirrhosis were of similar magnitude as those observed with significant fibrosis. CONCLUSIONS: In HIV-infected persons, liver fibrosis is associated with discordant peripheral CD4(+) lymphocyte results, especially in the setting of marked lymphopenia. Clinicians should also consider CD4% when interpreting absolute CD4(+) counts of HIV-infected persons with known or suspected liver disease, particularly if TLC is <1200 cells/µL.

Health related quality of life in adolescents with bladder exstrophy-epispadias as measured by the Child Health Questionnaire-Child Form 87.

PURPOSE: We determined health related quality of life as reported by adolescents with bladder exstrophy or epispadias using a validated generic instrument. MATERIALS AND METHODS: Adolescents age 11 to 18 years with bladder exstrophy or epispadias (57) completed a validated, generic, health related quality of life instrument, the CHQ-CF87 (Child Health Questionnaire-Child Form 87). Urinary incontinence, catheterization status, and medical and surgical history data were also obtained. Mean summary scores and 95% CIs for each subdomain of the CHQ-CF87 were calculated, and descriptively compared to 2 population based samples. In our sample health related quality of life outcomes by continence status were compared using univariate and multivariate analysis. However, this analysis was limited by a small sample size. RESULTS: Mean age of the 49 patients with bladder exstrophy and the 8 with epispadias was 14.3 years, 67% were male and 81% were Caucasian. There were 31 participants who reported incontinence and the median number of lifetime surgeries was 9. The exstrophy population scored well in all subdomains of the instrument when descriptively compared to 2 large samples of adolescent populations. In our sample incontinent patients had lower scores by multivariate analysis in 7 of 10 domains and better scores in 3 of 10 domains, although these differences were not statistically significant. CONCLUSIONS: Adolescents with bladder exstrophy and epispadias reported relatively good scores on the CHQ-CF87 when descriptively compared to other reference populations. This finding suggests that these children adapt well to the challenges of their condition. Analysis of the association of incontinence with health related quality of life was limited by the small sample size.