Publications by authors named "Christine E Chaisson"

42 Publications

Quality of Buprenorphine Care for Insured Adults With Opioid Use Disorder.

Med Care 2021 May;59(5):393-401

Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.

Aim: The aim of this study was to characterize quality of buprenorphine care for opioid use disorder (OUD) by quantifying buprenorphine initiation, engagement, and maintenance for individuals in a large, diverse, real-world cohort in the United States.

Design: This was a retrospective cohort analysis.

Setting: OUD treatment in the outpatient setting.

Participants: A total of 45,210 commercially insured and Medicare Advantage (MA) enrollees 18 years or older in the OptumLabs Data Warehouse with an index diagnosis of OUD between January 1, 2018 and December 31, 2018.

Interventions: Treatment with buprenorphine.

Measurements: We calculated 6 measures of buprenorphine treatment quality. We conducted survival analyses to characterize treatment duration and logistic regressions to evaluate the association between clinical and sociodemographic characteristics and quality.

Findings: Of 45,210 eligible individuals with OUD, ∼1 in 10 (n=4600, 10.2%) initiated buprenorphine within 365 days following diagnosis (Measure #1) and 2850 individuals (6.3%) initiated buprenorphine within 14 days of diagnosis (Measure #2). Of individuals initiating treatment within 14 days of diagnosis, 1769 (62.1%) had 2 or more buprenorphine claims within 34 days of initiation (Measure #3). Of the 4600 individuals who received buprenorphine, 2300 (50.0%) were maintained in care with 180 days or more of covered buprenorphine treatment during 365 days after diagnosis (Measure #4). Finally, of the 4600 individuals who received buprenorphine, 2543 (55.3%) did not fill any other concurrent opioid analgesic (Measure #5) and 2951 (64.2%) did not fill any concurrent benzodiazepine (Measure #6). Quality was generally lower for individuals with MA compared with commercial coverage and among Hispanic and Black adults compared with White adults.

Conclusion: Widespread gaps exist in quality of buprenorphine treatment initiation, engagement, and maintenance among commercially insured and MA enrollees with OUD.
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http://dx.doi.org/10.1097/MLR.0000000000001530DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026663PMC
May 2021

Relative Cost Differences of Initial Treatment Strategies for Newly Diagnosed Opioid Use Disorder: A Cohort Study.

Med Care 2020 10;58(10):919-926

UnitedHealthcare, Minnesota, MN.

Background: Relative costs of care among treatment options for opioid use disorder (OUD) are unknown.

Methods: We identified a cohort of 40,885 individuals with a new diagnosis of OUD in a large national de-identified claims database covering commercially insured and Medicare Advantage enrollees. We assigned individuals to 1 of 6 mutually exclusive initial treatment pathways: (1) Inpatient Detox/Rehabilitation Treatment Center; (2) Behavioral Health Intensive, intensive outpatient or Partial Hospitalization Services; (3) Methadone or Buprenorphine; (4) Naltrexone; (5) Behavioral Health Outpatient Services, or; (6) No Treatment. We assessed total costs of care in the initial 90 day treatment period for each strategy using a differences in differences approach controlling for baseline costs.

Results: Within 90 days of diagnosis, 94.8% of individuals received treatment, with the initial treatments being: 15.8% for Inpatient Detox/Rehabilitation Treatment Center, 4.8% for Behavioral Health Intensive, Intensive Outpatient or Partial Hospitalization Services, 12.5% for buprenorphine/methadone, 2.4% for naltrexone, and 59.3% for Behavioral Health Outpatient Services. Average unadjusted costs increased from $3250 per member per month (SD $7846) at baseline to $5047 per member per month (SD $11,856) in the 90 day follow-up period. Compared with no treatment, initial 90 day costs were lower for buprenorphine/methadone [Adjusted Difference in Differences Cost Ratio (ADIDCR) 0.65; 95% confidence interval (CI), 0.52-0.80], naltrexone (ADIDCR 0.53; 95% CI, 0.42-0.67), and behavioral health outpatient (ADIDCR 0.54; 95% CI, 0.44-0.66). Costs were higher for inpatient detox (ADIDCR 2.30; 95% CI, 1.88-2.83).

Conclusion: Improving health system capacity and insurance coverage and incentives for outpatient management of OUD may reduce health care costs.
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http://dx.doi.org/10.1097/MLR.0000000000001394DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7641182PMC
October 2020

Assessment of Potentially Inappropriate Prescribing of Opioid Analgesics Requiring Prior Opioid Tolerance.

JAMA Netw Open 2020 04 1;3(4):e202875. Epub 2020 Apr 1.

Previously with OptumLabs, Cambridge, Massachusetts.

Importance: Opioid-tolerant only (OTO) medications, such as transmucosal immediate-release fentanyl products and certain extended-release opioid analgesics, require prior opioid tolerance for safe use, as patients without tolerance may be at increased risk of overdose. Studies using insurance claims have found that many patients initiating these medications do not appear to be opioid tolerant.

Objectives: To measure prevalence of opioid tolerance in patients initiating OTO medications and to determine whether linked electronic health record (EHR) data contribute evidence of opioid tolerance not found in insurance claims data.

Design, Setting, And Participants: This retrospective cohort study used a national database of deidentified longitudinal health information, including medical and pharmacy claims, insurance enrollment, and EHR data, from January 1, 2007, to December 31, 2016. Data included 131 756 US residents with at least 183 days of continuous enrollment in commercial or Medicare Advantage insurance (including medical and pharmacy benefits) who had received an OTO medication and who had no inpatient stays in the 30 days prior to starting an OTO medication; of these, 20 044 individuals had linked EHR data within the prior 183 days. Data were analyzed from July 1, 2017, to August 31, 2018.

Exposures: Initiating an OTO medication.

Main Outcomes And Measures: Prior opioid tolerance demonstrated through pharmacy fills or EHR data on prescriptions written.

Results: Among 153 385 OTO use episodes identified, 89 029 (58.0%) occurred among women, 62 900 (41.0%) occurred among patients with Medicare Advantage insurance, 39 394 (25.7%) occurred in the Midwest, 17 366 (11.3%) occurred in the Northeast, 73 316 (47.8%) occurred in the South, and 23 309 (15.2%) occurred in the West. Less than half of use episodes (73 117 episodes [47.7%]) involved patients with evidence in claims data of opioid tolerance prior to initiating therapy with an OTO medication, including 31 392 of 101 676 episodes (30.9%) involving transdermal fentanyl, 1561 of 2440 episodes (64.0%) involving transmucosal fentanyl, 36 596 of 43 559 episodes (84.0%) involving extended-release oxycodone, and 3568 of 5710 episodes (62.5%) involving extended-release hydromorphone. Among 20 044 OTO use episodes with linked EHR and claims data, less than 1% of OTO episodes identified in claims had evidence of opioid tolerance in structured EHR data that was not present in claims data (108 episodes [0.5%]). After limiting the sample to OTO episodes identified in claims with a matching OTO prescription within 14 days in the structured EHR data, only 40 of 939 episodes (4.0%) occurred among patients with evidence of tolerance that was not present in claims data.

Conclusions And Relevance: This cohort study found that most patients initiating OTO medications did not have evidence of prior opioid tolerance, suggesting they were at increased risk of opioid-related harms, including fatal overdose. Data from EHRs did not contribute substantial additional evidence of opioid tolerance beyond the data found in prescription claims. Future research is needed to understand the clinical rationale behind these observed prescribing patterns and to quantify the risk of harm to patients associated with potentially inappropriate prescribing.
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http://dx.doi.org/10.1001/jamanetworkopen.2020.2875DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7160686PMC
April 2020

Comparative Effectiveness of Different Treatment Pathways for Opioid Use Disorder.

JAMA Netw Open 2020 02 5;3(2):e1920622. Epub 2020 Feb 5.

Department of Medicare and Retirement, United Healthcare, Minnetonka, Minnesota.

Importance: Although clinical trials demonstrate the superior effectiveness of medication for opioid use disorder (MOUD) compared with nonpharmacologic treatment, national data on the comparative effectiveness of real-world treatment pathways are lacking.

Objective: To examine associations between opioid use disorder (OUD) treatment pathways and overdose and opioid-related acute care use as proxies for OUD recurrence.

Design, Setting, And Participants: This retrospective comparative effectiveness research study assessed deidentified claims from the OptumLabs Data Warehouse from individuals aged 16 years or older with OUD and commercial or Medicare Advantage coverage. Opioid use disorder was identified based on 1 or more inpatient or 2 or more outpatient claims for OUD diagnosis codes within 3 months of each other; 1 or more claims for OUD plus diagnosis codes for opioid-related overdose, injection-related infection, or inpatient detoxification or residential services; or MOUD claims between January 1, 2015, and September 30, 2017. Data analysis was performed from April 1, 2018, to June 30, 2019.

Exposures: One of 6 mutually exclusive treatment pathways, including (1) no treatment, (2) inpatient detoxification or residential services, (3) intensive behavioral health, (4) buprenorphine or methadone, (5) naltrexone, and (6) nonintensive behavioral health.

Main Outcomes And Measures: Opioid-related overdose or serious acute care use during 3 and 12 months after initial treatment.

Results: A total of 40 885 individuals with OUD (mean [SD] age, 47.73 [17.25] years; 22 172 [54.2%] male; 30 332 [74.2%] white) were identified. For OUD treatment, 24 258 (59.3%) received nonintensive behavioral health, 6455 (15.8%) received inpatient detoxification or residential services, 5123 (12.5%) received MOUD treatment with buprenorphine or methadone, 1970 (4.8%) received intensive behavioral health, and 963 (2.4%) received MOUD treatment with naltrexone. During 3-month follow-up, 707 participants (1.7%) experienced an overdose, and 773 (1.9%) had serious opioid-related acute care use. Only treatment with buprenorphine or methadone was associated with a reduced risk of overdose during 3-month (adjusted hazard ratio [AHR], 0.24; 95% CI, 0.14-0.41) and 12-month (AHR, 0.41; 95% CI, 0.31-0.55) follow-up. Treatment with buprenorphine or methadone was also associated with reduction in serious opioid-related acute care use during 3-month (AHR, 0.68; 95% CI, 0.47-0.99) and 12-month (AHR, 0.74; 95% CI, 0.58-0.95) follow-up.

Conclusions And Relevance: Treatment with buprenorphine or methadone was associated with reductions in overdose and serious opioid-related acute care use compared with other treatments. Strategies to address the underuse of MOUD are needed.
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http://dx.doi.org/10.1001/jamanetworkopen.2019.20622DOI Listing
February 2020

A strengths-based case management intervention to link HIV-positive people who inject drugs in Russia to HIV care.

AIDS 2019 07;33(9):1467-1476

First Pavlov State Medical University of St. Petersburg, St. Petersburg, Russian Federation.

Objective: To determine whether the Linking Infectious and Narcology Care strengths-based case management intervention was more effective than usual care for linking people who inject drugs (PWID) to HIV care and improving HIV outcomes.

Design: Two-armed randomized controlled trial.

Setting: Participants recruited from a narcology hospital in St. Petersburg, Russia.

Participants: A total of 349 HIV-positive PWID not on antiretroviral therapy (ART).

Intervention: Strengths-based case management over 6 months.

Main Outcome Measures: Primary outcomes were linkage to HIV care and improved CD4 cell count. We performed adjusted logistic and linear regression analyses controlling for past HIV care using the intention-to-treat approach.

Results: Participants (N = 349) had the following baseline characteristics: 73% male, 12% any past ART use, and median values of 34.0 years of age and CD4 cell count 311 cells/μl. Within 6 months of enrollment 51% of the intervention group and 31% of controls linked to HIV care (adjusted odds ratio 2.34; 95% confidence interval: 1.49-3.67; P < 0.001). Mean CD4 cell count at 12 months was 343 and 354 cells/μl in the intervention and control groups, respectively (adjusted ratio of means 1.14; 95% confidence interval: 0.91, 1.42, P = 0.25).

Conclusion: The Linking Infectious and Narcology Care strengths-based case management intervention was more effective than usual care in linking Russian PWID to HIV care, but did not improve CD4 cell count, likely due to low overall ART initiation. Although case management can improve linkage to HIV care, specific approaches to initiate and adhere to ART are needed to improve clinical outcomes (e.g., increased CD4 cell count) in this population.
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http://dx.doi.org/10.1097/QAD.0000000000002230DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6635053PMC
July 2019

A magnetic resonance spectroscopy investigation in symptomatic former NFL players.

Brain Imaging Behav 2020 Oct;14(5):1419-1429

Center for Clinical Spectroscopy, Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, 4 Blackfan Street HIM-820, Boston, MA, 02115, USA.

The long-term neurologic consequences of exposure to repetitive head impacts (RHI) are not well understood. This study used magnetic resonance spectroscopy (MRS) to examine later-life neurochemistry and its association with RHI and clinical function in former National Football League (NFL) players. The sample included 77 symptomatic former NFL players and 23 asymptomatic individuals without a head trauma history. Participants completed cognitive, behavior, and mood measures. N-acetyl aspartate, glutamate/glutamine, choline, myo-inositol, creatine, and glutathione were measured in the posterior (PCG) and anterior (ACG) cingulate gyrus, and parietal white matter (PWM). A cumulative head impact index (CHII) estimated RHI. In former NFL players, a higher CHII correlated with lower PWM creatine (r = -0.23, p = 0.02). Multivariate mixed-effect models examined neurochemical differences between the former NFL players and asymptomatic individuals without a history of head trauma. PWM N-acetyl aspartate was lower among the former NFL players (mean diff. = 1.02, p = 0.03). Between-group analyses are preliminary as groups were recruited based on symptomatic status. The ACG was the only region associated with clinical function, including positive correlations between glutamate (r = 0.32, p = 0.004), glutathione (r = 0.29, p = 0.02), and myo-inositol (r = 0.26, p = 0.01) with behavioral/mood symptoms. Other positive correlations between ACG neurochemistry and clinical function emerged (i.e., behavioral/mood symptoms, cognition), but the positive directionality was unexpected. All analyses controlled for age, body mass index, and education (for analyses examining clinical function). In this sample of symptomatic former NFL players, there was a direct effect between RHI and reduced cellular energy metabolism (i.e., lower creatine). MRS neurochemicals associated with neuroinflammation also correlated with behavioral/mood symptoms.
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http://dx.doi.org/10.1007/s11682-019-00060-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6994233PMC
October 2020

Automated versus manual segmentation of brain region volumes in former football players.

Neuroimage Clin 2018 21;18:888-896. Epub 2018 Mar 21.

Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States; Department of Child and Adolescent Psychiatry, Psychosomatic, and Psychotherapy, Ludwig-Maximilian-University, Munich, Germany. Electronic address:

Objectives: To determine whether or not automated FreeSurfer segmentation of brain regions considered important in repetitive head trauma can be analyzed accurately without manual correction.

Materials And Methods: 3 T MR neuroimaging was performed with automated FreeSurfer segmentation and manual correction of 11 brain regions in former National Football League (NFL) players with neurobehavioral symptoms and in control subjects. Automated segmentation and manually-corrected volumes were compared using an intraclass correlation coefficient (ICC). Linear mixed effects regression models were also used to estimate between-group mean volume comparisons and to correlate former NFL player brain volumes with neurobehavioral factors.

Results: Eighty-six former NFL players (55.2 ± 8.0 years) and 22 control subjects (57.0 ± 6.6 years) were evaluated. ICC was highly correlated between automated and manually-corrected corpus callosum volumes (0.911), lateral ventricular volumes (right 0.980, left 0.967), and amygdala-hippocampal complex volumes (right 0.713, left 0.731), but less correlated when amygdalae (right -0.170, left -0.090) and hippocampi (right 0.539, left 0.637) volumes were separately delineated and also less correlated for cingulate gyri volumes (right 0.639, left 0.351). Statistically significant differences between former NFL player and controls were identified in 8 of 11 regions with manual correction but in only 4 of 11 regions without such correction. Within NFL players, manually corrected brain volumes were significantly associated with 3 neurobehavioral factors, but a different set of 3 brain regions and neurobehavioral factor correlations was observed for brain region volumes segmented without manual correction.

Conclusions: Automated FreeSurfer segmentation of the corpus callosum, lateral ventricles, and amygdala-hippocampus complex may be appropriate for analysis without manual correction. However, FreeSurfer segmentation of the amygdala, hippocampus, and cingulate gyrus need further manual correction prior to performing group comparisons and correlations with neurobehavioral measures.
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http://dx.doi.org/10.1016/j.nicl.2018.03.026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5988230PMC
January 2019

Age of first exposure to tackle football and chronic traumatic encephalopathy.

Ann Neurol 2018 05;83(5):886-901

Boston University Alzheimer's Disease and CTE Center, Department of Neurology, Boston University School of Medicine, Boston, MA.

Objective: To examine the effect of age of first exposure to tackle football on chronic traumatic encephalopathy (CTE) pathological severity and age of neurobehavioral symptom onset in tackle football players with neuropathologically confirmed CTE.

Methods: The sample included 246 tackle football players who donated their brains for neuropathological examination. Two hundred eleven were diagnosed with CTE (126 of 211 were without comorbid neurodegenerative diseases), and 35 were without CTE. Informant interviews ascertained age of first exposure and age of cognitive and behavioral/mood symptom onset.

Results: Analyses accounted for decade and duration of play. Age of exposure was not associated with CTE pathological severity, or Alzheimer's disease or Lewy body pathology. In the 211 participants with CTE, every 1 year younger participants began to play tackle football predicted earlier reported cognitive symptom onset by 2.44 years (p < 0.0001) and behavioral/mood symptoms by 2.50 years (p < 0.0001). Age of exposure before 12 predicted earlier cognitive (p < 0.0001) and behavioral/mood (p < 0.0001) symptom onset by 13.39 and 13.28 years, respectively. In participants with dementia, younger age of exposure corresponded to earlier functional impairment onset. Similar effects were observed in the 126 CTE-only participants. Effect sizes were comparable in participants without CTE.

Interpretation: In this sample of deceased tackle football players, younger age of exposure to tackle football was not associated with CTE pathological severity, but predicted earlier neurobehavioral symptom onset. Youth exposure to tackle football may reduce resiliency to late-life neuropathology. These findings may not generalize to the broader tackle football population, and informant-report may have affected the accuracy of the estimated effects. Ann Neurol 2018;83:886-901.
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http://dx.doi.org/10.1002/ana.25245DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6367933PMC
May 2018

Design of a randomized controlled trial of zinc supplementation to improve markers of mortality and HIV disease progression in HIV-positive drinkers in St. Petersburg, Russia.

HIV Clin Trials 2018 06 17;19(3):101-111. Epub 2018 Apr 17.

i Department of Medicine, Section of General Internal Medicine, School of Medicine/Boston Medical Center, Clinical Addiction Research and Education (CARE) Unit , Boston University , Boston , MA , USA.

Background Russia continues to have an uncontrolled HIV epidemic and its per capita alcohol consumption is among the highest in the world. Alcohol use among HIV-positive individuals is common and is associated with worse clinical outcomes. Alcohol use and HIV each lead to microbial translocation, which in turn results in inflammation. Zinc supplementation holds potential for lowering levels of biomarkers of inflammation, possibly as a consequence of its impact on intestinal permeability. This paper describes the protocol of a double-blinded randomized placebo-controlled trial of zinc supplementation in St. Petersburg, Russia. Methods Participants (n = 254) were recruited between October 2013 and June 2015 from HIV and addiction clinical care sites, and non-clinical sites in St. Petersburg, Russia. Participants were randomly assigned, to receive either zinc (15 mg for men; 12 mg for women) or placebo, daily for 18 months. The following outcomes were assessed at 6, 12, and 18 months: (1) mortality risk (primary outcome at 18 months); (2) HIV disease progression; (3) cardiovascular risk; and (4) microbial translocation and inflammation. Adherence was assessed using direct (riboflavin) and indirect (pill count, self-report) measures. Conclusion Given the limited effectiveness of current interventions to reduce alcohol use, zinc supplementation merits testing as a simple, low-cost intervention to mitigate the consequences of alcohol use in HIV-positive persons despite ongoing drinking.
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http://dx.doi.org/10.1080/15284336.2018.1459344DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5957784PMC
June 2018

White matter signal abnormalities in former National Football League players.

Alzheimers Dement (Amst) 2018 6;10:56-65. Epub 2017 Nov 6.

Boston University Alzheimer's Disease and CTE Center, Department of Neurology, Boston University School of Medicine, Boston, MA, USA.

Introduction: Later-life brain alterations in former tackle football players are poorly understood, particularly regarding their relationship with repetitive head impacts (RHIs) and clinical function. We examined white matter signal abnormalities (WMSAs) and their association with RHIs and clinical function in former National Football League (NFL) players.

Methods: Eighty-six clinically symptomatic former NFL players and 23 same-age reportedly asymptomatic controls without head trauma exposure underwent magnetic resonance imaging and neuropsychological testing. FreeSurfer calculated WMSAs. A cumulative head impact index quantified RHIs.

Results: In former NFL players, increased volume of WMSAs was associated with higher cumulative head impact index scores ( = .043) and worse psychomotor speed and executive function ( = .015). Although former NFL players had greater WMSA volume than controls ( = .046), these findings are inconclusive due to recruitment of controls based on lack of clinical symptoms and head trauma exposure.

Discussion: In former NFL players, WMSAs may reflect long-term microvascular and nonmicrovascular pathologies from RHIs that negatively impact cognition.
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http://dx.doi.org/10.1016/j.dadm.2017.10.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5699890PMC
November 2017

Clinical Utility of Select Neuropsychological Assessment Battery Tests in Predicting Functional Abilities in Dementia.

Arch Clin Neuropsychol 2018 Aug;33(5):530-540

Boston University Alzheimer's Disease and CTE Center, Boston University School of Medicine, Boston, Massachusetts, USA.

Objective: Neuropsychological test performance can provide insight into functional abilities in patients with dementia, particularly in the absence of an informant. The relationship between neuropsychological measures and instrumental activities of daily living (IADLs) is unclear due to hetereogeneity in cognitive domains assessed and neuropsychological tests administered. Practical and ecologically valid performance-based measures of IADLs are also limited. The Neuropsychological Assessment Battery (NAB) is uniquely positioned to provide a dual-purpose assessment of cognitive and IADL function, as it includes Daily Living tests that simulate real-world functional tasks. We examined the utility of select NAB tests in predicting informant-reported IADLs in mild cognitive impairment and dementia.

Methods: The sample of 327 participants included 128 normal controls, 97 individuals with mild cognitive impairment, and 102 individuals with Alzheimer's disease dementia from the Boston University Alzheimer's Disease Center research registry. Informants completed the Lawton Brody Instrumental Activities of Daily Living Scale, and study participants were administered selected NAB tests that were complementary to the existing protocol.

Results: ROC curves showed strongest prediction of IADL (AUC > 0.90) for memory measures (List Learning delayed recall and Daily Living Memory delayed recall) and Daily Living Driving Scenes. At a predetermined level of specificity (95%), List Learning delayed recall (71%) and Daily Living Memory delayed recall (88%) were the most sensitive. The Daily Living Memory and Driving Scenes tests strongly predicted IADL status, and the other Daily Living tests contributed unique variance.

Conclusions: NAB memory measures and Daily Living Tests may have clinical utility in detecting informant-rated functional impairment in dementia.
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http://dx.doi.org/10.1093/arclin/acx100DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6116785PMC
August 2018

Age at First Exposure to Repetitive Head Impacts Is Associated with Smaller Thalamic Volumes in Former Professional American Football Players.

J Neurotrauma 2018 01 17;35(2):278-285. Epub 2017 Nov 17.

1 Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital , Harvard Medical School, Boston, Massachusetts.

Thalamic atrophy has been associated with exposure to repetitive head impacts (RHI) in professional fighters. The aim of this study is to investigate whether or not age at first exposure (AFE) to RHI is associated with thalamic volume in symptomatic former National Football League (NFL) players at risk for chronic traumatic encephalopathy (CTE). Eighty-six symptomatic former NFL players (mean age = 54.9 ± 7.9 years) were included. T1-weighted data were acquired on a 3T magnetic resonance imager, and thalamic volumes were derived using FreeSurfer. Mood and behavior, psychomotor speed, and visual and verbal memory were assessed. The association between thalamic volume and AFE to playing football and to number of years playing was calculated. Decreased thalamic volume was associated with more years of play (left: p = 0.03; right: p = 0.03). Younger AFE was associated with decreased right thalamic volume (p = 0.014). This association remained significant after adjusting for total years of play. Decreased left thalamic volume was associated with worse visual memory (p = 0.014), whereas increased right thalamic volume was associated with fewer mood and behavior symptoms (p = 0.003). In our sample of symptomatic former NFL players at risk for CTE, total years of play and AFE were associated with decreased thalamic volume. The effect of AFE on right thalamic volume was almost twice as strong as the effect of total years of play. Our findings confirm previous reports of an association between thalamic volume and exposure to RHI. They suggest further that younger AFE may result in smaller thalamic volume later in life.
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http://dx.doi.org/10.1089/neu.2017.5145DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5784796PMC
January 2018

Use of an android phone application for automated text messages in international settings: A case study in an HIV clinical trial in St. Petersburg, Russia.

Clin Trials 2018 02 10;15(1):36-43. Epub 2017 Aug 10.

1 Data Coordinating Center, School of Public Health, Boston University, Boston, MA, USA.

Background/aims: Reproducible outcomes in clinical trials depend on adherence to study protocol. Short message service (also known as text message) reminders have been shown to improve clinical trial adherence in the United States and elsewhere. However, due to systematic differences in mobile data plans, languages, and technology, these systems are not easily translated to international settings.

Methods: To gauge technical capabilities for international projects, we developed SMSMessenger, an automated Android application that uses a US server to send medication reminders to participants in a clinical trial in St. Petersburg, Russia (Zinc for HIV disease among alcohol users-a randomized controlled trial in the Russia Alcohol Research Collaboration on HIV/AIDS cohort). The application is downloaded once onto an Android study phone. When it is time for the text message reminders to be sent, study personnel access the application on a local phone, which in turn accesses the existing clinical trial database hosted on a US web server. The application retrieves a list of participants with the following information: phone number, whether a message should be received at that time, and the appropriate text of the message. The application is capable of storing multiple outgoing messages. With a few clicks, text messages are sent to study participants who can reply directly to the message. Study staff can check the local phone for incoming messages. The SMSMessenger application uses an existing clinical trial database and is able to receive real-time updates. All communications between the application and server are encrypted, and phone numbers are stored in a secure database behind a firewall. No sensitive data are stored on the phone, as outgoing messages are sent through the application and not by messaging features on the phone itself. Messages are sent simultaneously to study participants, which reduces the burden on local study staff. Costs and setup are minimal. The only local requirements are an Android phone and data plan.

Conclusion: The SMSMessenger technology could be modified to be applied anywhere in the world, in any language, script, or alphabet, and for many different purposes. The novel application of this existing low-cost technology can improve the usefulness of text messaging in advancing the goals of international clinical trials.
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http://dx.doi.org/10.1177/1740774517726067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5794610PMC
February 2018

Clinicopathological Evaluation of Chronic Traumatic Encephalopathy in Players of American Football.

JAMA 2017 07;318(4):360-370

Boston University Alzheimer's Disease and CTE Center, Boston University School of Medicine, Boston, Massachusetts2Department of Neurology, Boston University School of Medicine, Boston, Massachusetts4VA Boston Healthcare System, US Department of Veteran Affairs, Boston, Massachusetts5Department of Veterans Affairs Medical Center, Bedford, Massachusetts12Department of Pathology, Boston University School of Medicine, Boston, Massachusetts23Boston University School of Medicine, Boston, Massachusetts.

Importance: Players of American football may be at increased risk of long-term neurological conditions, particularly chronic traumatic encephalopathy (CTE).

Objective: To determine the neuropathological and clinical features of deceased football players with CTE.

Design, Setting, And Participants: Case series of 202 football players whose brains were donated for research. Neuropathological evaluations and retrospective telephone clinical assessments (including head trauma history) with informants were performed blinded. Online questionnaires ascertained athletic and military history.

Exposures: Participation in American football at any level of play.

Main Outcomes And Measures: Neuropathological diagnoses of neurodegenerative diseases, including CTE, based on defined diagnostic criteria; CTE neuropathological severity (stages I to IV or dichotomized into mild [stages I and II] and severe [stages III and IV]); informant-reported athletic history and, for players who died in 2014 or later, clinical presentation, including behavior, mood, and cognitive symptoms and dementia.

Results: Among 202 deceased former football players (median age at death, 66 years [interquartile range, 47-76 years]), CTE was neuropathologically diagnosed in 177 players (87%; median age at death, 67 years [interquartile range, 52-77 years]; mean years of football participation, 15.1 [SD, 5.2]), including 0 of 2 pre-high school, 3 of 14 high school (21%), 48 of 53 college (91%), 9 of 14 semiprofessional (64%), 7 of 8 Canadian Football League (88%), and 110 of 111 National Football League (99%) players. Neuropathological severity of CTE was distributed across the highest level of play, with all 3 former high school players having mild pathology and the majority of former college (27 [56%]), semiprofessional (5 [56%]), and professional (101 [86%]) players having severe pathology. Among 27 participants with mild CTE pathology, 26 (96%) had behavioral or mood symptoms or both, 23 (85%) had cognitive symptoms, and 9 (33%) had signs of dementia. Among 84 participants with severe CTE pathology, 75 (89%) had behavioral or mood symptoms or both, 80 (95%) had cognitive symptoms, and 71 (85%) had signs of dementia.

Conclusions And Relevance: In a convenience sample of deceased football players who donated their brains for research, a high proportion had neuropathological evidence of CTE, suggesting that CTE may be related to prior participation in football.
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http://dx.doi.org/10.1001/jama.2017.8334DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5807097PMC
July 2017

HIV Stigma and Substance Use Among HIV-Positive Russians with Risky Drinking.

AIDS Behav 2017 Sep;21(9):2618-2627

Boston University School of Medicine and Boston Medical Center, Boston, MA, USA.

The link between HIV stigma with substance use is understudied. We characterized individuals with high HIV stigma and examined whether HIV stigma contributes to substance use among HIV-positive Russians reporting risky alcohol use. We analyzed data from HERMITAGE, a randomized controlled trial of 700 people living with HIV/AIDS (PLWHA) with past 6-month risky sex and risky alcohol use in St. Petersburg, Russia (2007-2011). Participants who were female and reported depressive symptoms and lower social support were more likely to endorse high HIV stigma (all p's < 0.001). In adjusted models, high HIV stigma was not significantly associated with the primary outcome unhealthy substance use and was not consistently associated with secondary substance use outcomes. Interventions to enhance social and mental health support for PLWHA, particularly women, may reduce stigma, though such reductions may not correspond to substantial decreases in substance use among this population.
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http://dx.doi.org/10.1007/s10461-017-1832-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5856479PMC
September 2017

Modeling the Relationships Among Late-Life Body Mass Index, Cerebrovascular Disease, and Alzheimer's Disease Neuropathology in an Autopsy Sample of 1,421 Subjects from the National Alzheimer's Coordinating Center Data Set.

J Alzheimers Dis 2017 ;57(3):953-968

Boston University Alzheimer's Disease and CTE Center, Boston University School of Medicine, Boston, MA, USA.

The relationship between late-life body mass index (BMI) and Alzheimer's disease (AD) is poorly understood due to the lack of research in samples with autopsy-confirmed AD neuropathology (ADNP). The role of cerebrovascular disease (CVD) in the interplay between late-life BMI and ADNP is unclear. We conducted a retrospective longitudinal investigation and used joint modeling of linear mixed effects to investigate causal relationships among repeated antemortem BMI measurements, CVD (quantified neuropathologically), and ADNP in an autopsy sample of subjects across the AD clinical continuum. The sample included 1,421 subjects from the National Alzheimer's Coordinating Center's Uniform Data Set and Neuropathology Data Set with diagnoses of normal cognition (NC; n = 234), mild cognitive impairment (MCI; n = 201), or AD dementia (n = 986). ADNP was defined as moderate to frequent neuritic plaques and Braak stageIII-VI. Ischemic Injury Scale (IIS) operationalized CVD. Joint modeling examined relationships among BMI, IIS, and ADNP in the overall sample and stratified by initial visit Clinical Dementia Rating score. Subject-specific random intercept for BMI was the predictor for ADNP due to minimal BMI change (p = 0.3028). Analyses controlling for demographic variables and APOE ɛ4 showed lower late-life BMI predicted increased odds of ADNP in the overall sample (p < 0.001), and in subjects with CDR of 0 (p = 0.0021) and 0.5 (p = 0.0012), but not ≥1.0 (p = 0.2012). Although higher IIS predicted greater odds of ADNP (p < 0.0001), BMI did not predict IIS (p = 0.2814). The current findings confirm lower late-life BMI confers increased odds for ADNP. Lower late-life BMI may be a preclinical indicator of underlying ADNP.
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http://dx.doi.org/10.3233/JAD-161205DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5526463PMC
August 2017

Repetitive head impact exposure and later-life plasma total tau in former National Football League players.

Alzheimers Dement (Amst) 2017 10;7:33-40. Epub 2016 Dec 10.

Boston University Alzheimer's Disease and CTE Center, Boston University School of Medicine, Boston, MA, USA; Department of Neurology, Boston University School of Medicine, Boston, MA, USA; Department of Neurosurgery, Boston University School of Medicine, Boston, MA, USA; Department of Anatomy and Neurobiology, Boston University School of Medicine, Boston, MA, USA.

Introduction: Blood protein analysis of total tau (t-tau) may be a practical screening biomarker for chronic traumatic encephalopathy (CTE), a neurodegenerative tauopathy associated with repetitive head impact (RHI) exposure. We examined plasma t-tau in symptomatic former National Football League (NFL) players compared with controls and the relationship between RHI exposure and later-life plasma t-tau.

Methods: Ninety-six former NFL players (age 40-69) and 25 same-age controls underwent blood draw to determine plasma t-tau levels. The cumulative head impact index (CHII) quantified RHI exposure. Subjects completed measures of clinical function.

Results: A higher CHII predicted greater plasma t-tau in the former NFL players ( = .0137). No group differences in plasma t-tau emerged, but a concentration ≥3.56 pg/mL was 100% specific to former NFL players. Plasma t-tau did not predict clinical function.

Discussion: Greater RHI exposure predicted higher later-life plasma t-tau concentrations, and further study on plasma t-tau as a candidate screening biomarker for CTE is warranted.
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http://dx.doi.org/10.1016/j.dadm.2016.11.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5312499PMC
December 2016

Insights on the Russian HCV Care Cascade: Minimal HCV Treatment for HIV/HCV Co-infected PWID in St. Petersburg.

Hepatol Med Policy 2016 11;1. Epub 2016 Oct 11.

Department of Medicine, Section of General Internal Medicine, Clinical Addiction Research and Education Unit, Boston University School of Medicine/Boston Medical Center, 801 Massachusetts Avenue, 2nd Floor, Boston, MA 02118, USA; Department of Community Health Sciences, Boston University School of Public Health, 801 Massachusetts Avenue, 2nd Floor, Boston, MA 02118, USA.

Background: The human immunodeficiency virus (HIV) epidemic in Russia, driven by injection drug use, has seen a steady rise in the past two decades. Hepatitis C virus (HCV) infection is highly prevalent in people who inject drugs (PWID). The study aimed to describe the current frequency of HCV testing and treatment among HIV-infected PWID in St. Petersburg, Russia.

Methods: This study examined baseline data from the "Linking Infectious and Narcology Care" (LINC) and "Russia Alcohol Research Collaboration on HIV/AIDS" (Russia ARCH) studies. Participants included in this analysis were HIV-infected with a history of injection drug use. Descriptive statistics were performed to assess frequency of HCV testing and treatment.

Results: Participants (n=349 [LINC], 207 [Russia ARCH]) had a mean age of 33.8 years (IQR: 31-37) in LINC and 33.0 (IQR: 30-36) in Russia ARCH; 26.6% (LINC) and 29.0% (Russia ARCH) were female; 100% were Caucasian. Nearly all participants had been tested for HCV (98.9% in LINC, 97.1% in Russia ARCH). Almost all reported being diagnosed HCV positive (98.9% in LINC, 97.1% in Russia ARCH). Only 2.3% of LINC and 5.0% of Russia ARCH participants reported ever receiving HCV treatment.

Conclusions: Among these cohorts of HIV-infected PWID in St. Petersburg, Russia, as of 2015 nearly all reported being tested for HCV and testing positive, while only 3.3% received any HCV treatment. In this new era of effective HCV pharmacotherapy, an enormous chasm in the HCV treatment cascade in Russia exists providing substantial opportunities for curing HCV in HIV-infected Russians with a history of injection drug use.
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http://dx.doi.org/10.1186/s41124-016-0020-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5313079PMC
October 2016

Barriers to Care and 1-Year Mortality Among Newly Diagnosed HIV-Infected People in Durban, South Africa.

J Acquir Immune Defic Syndr 2017 04;74(4):432-438

*Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA; †Division of General Internal Medicine, Massachusetts General Hospital, Boston, MA; ‡Medical Practice Evaluation Center, Massachusetts General Hospital, Boston, MA; §Harvard Medical School, Boston, MA; ‖Harvard University Center for AIDS Research, Harvard University, Boston, MA; ¶Data Coordinating Center, Boston University School of Public Health, Boston, MA; #McCord Hospital, Durban, South Africa; **Division of General Pediatrics, Department of Medicine, Boston Children's Hospital, Boston, MA; ††RAND Corporation, Santa Monica, CA; ‡‡St. Mary's Hospital, Durban, South Africa; §§Division of Infectious Diseases, Brigham and Women's Hospital, Boston, MA; ‖‖Department of Epidemiology, Boston University School of Public Health, Boston, MA; ¶¶Department of Health Policy and Management, Harvard T.H. Chan School of Public Health, Boston, MA; ##Department of Orthopedic Surgery, Brigham and Women's Hospital, Boston, MA; and ***Department of Biostatistics, Boston University School of Public Health, Boston, MA.

Background: Prompt entry into HIV care is often hindered by personal and structural barriers. Our objective was to evaluate the impact of self-perceived barriers to health care on 1-year mortality among newly diagnosed HIV-infected individuals in Durban, South Africa.

Methods: Before HIV testing at 4 outpatient sites, adults (≥18 years) were surveyed regarding perceived barriers to care including (1) service delivery, (2) financial, (3) personal health perception, (4) logistical, and (5) structural. We assessed deaths via phone calls and the South African National Population Register. We used multivariable Cox proportional hazards models to determine the association between number of perceived barriers and death within 1 year.

Results: One thousand eight hundred ninety-nine HIV-infected participants enrolled. Median age was 33 years (interquartile range: 27-41 years), 49% were females, and median CD4 count was 192/μL (interquartile range: 72-346/μL). One thousand fifty-seven participants (56%) reported no, 370 (20%) reported 1-3, and 460 (24%) reported >3 barriers to care. By 1 year, 250 [13%, 95% confidence interval (CI): 12% to 15%] participants died. Adjusting for age, sex, education, baseline CD4 count, distance to clinic, and tuberculosis status, participants with 1-3 barriers (adjusted hazard ratio: 1.49, 95% CI: 1.06 to 2.08) and >3 barriers (adjusted hazard ratio: 1.81, 95% CI: 1.35 to 2.43) had higher 1-year mortality risk compared with those without barriers.

Conclusions: HIV-infected individuals in South Africa who reported perceived barriers to medical care at diagnosis were more likely to die within 1 year. Targeted structural interventions, such as extended clinic hours, travel vouchers, and streamlined clinic operations, may improve linkage to care and antiretroviral therapy initiation for these people.
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http://dx.doi.org/10.1097/QAI.0000000000001277DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5321110PMC
April 2017

Fatal and non-fatal overdose after narcology hospital discharge among Russians living with HIV/AIDS who inject drugs.

Int J Drug Policy 2017 01 28;39:114-120. Epub 2016 Nov 28.

Department of Medicine, Section of General Internal Medicine, Clinical Addiction Research and Education Unit, Boston University School of Medicine & Boston Medical Center, 801 Massachusetts Avenue, Boston, USA; Department of Community Health Sciences, Boston University School of Public Health, 801 Massachusetts Avenue, Boston, MA, USA.

Objectives: Among Russians living with HIV/AIDS who inject drugs, we examined the incidence of fatal and non-fatal overdoses following discharge from a narcology hospital and the associations with more advanced HIV infection.

Design: Prospective cohort study of data collected at baseline, 3 and 6 months from HIV-infected patients with a history of injection drug use who were not treated with anti-retroviral therapy. Participants were recruited between 2012-2014 from a narcology (addiction) hospital in St. Petersburg, Russia.

Methods: Fatal overdose was determined based on contact reports to study staff in the year after discharge. Non-fatal overdose was self-reported at the 3- and 6-month assessments. The main independent variable for HIV severity was CD4 cell count at the baseline interview (<200cells/mm≥200cells/mm). Secondary analyses assessed time since HIV diagnosis and treated with anti-retroviral treatment (ART) prior to enrolment as independent variables. We fit Cox proportional hazards models to assess whether HIV severity is associated with either fatal or non-fatal overdose.

Results: Among 349 narcology patients, 18 participants died from overdose within one year after discharge (8.7%, 95% CI 3.4-14.2 by Kaplan-Meier); an estimated 51% [95% CI 34-68%] reported at least one non-fatal overdose within 6 months of discharge. HIV severity, time since HIV diagnosis and ever ART were not significantly associated with either fatal or non-fatal overdose events.

Conclusion: Fatal and non-fatal overdose are common among Russians living with HIV/AIDS who inject drugs after narcology hospital discharge. Overdose prevention interventions are urgently warranted among Russian narcology patients with HIV infection.
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http://dx.doi.org/10.1016/j.drugpo.2016.10.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5191979PMC
January 2017

Practice Effects on Story Memory and List Learning Tests in the Neuropsychological Assessment of Older Adults.

PLoS One 2016 6;11(10):e0164492. Epub 2016 Oct 6.

Alzheimer's Disease Center, Boston University School of Medicine, Boston, Massachusetts, United States of America.

Two of the most commonly used methods to assess memory functioning in studies of cognitive aging and dementia are story memory and list learning tests. We hypothesized that the most commonly used story memory test, Wechsler's Logical Memory, would generate more pronounced practice effects than a well validated but less common list learning test, the Neuropsychological Assessment Battery (NAB) List Learning test. Two hundred eighty-seven older adults, ages 51 to 100 at baseline, completed both tests as part of a larger neuropsychological test battery on an annual basis. Up to five years of recall scores from participants who were diagnosed as cognitively normal (n = 96) or with mild cognitive impairment (MCI; n = 72) or Alzheimer's disease (AD; n = 121) at their most recent visit were analyzed with linear mixed effects regression to examine the interaction between the type of test and the number of times exposed to the test. Other variables, including age at baseline, sex, education, race, time (years) since baseline, and clinical diagnosis were also entered as fixed effects predictor variables. The results indicated that both tests produced significant practice effects in controls and MCI participants; in contrast, participants with AD declined or remained stable. However, for the delayed-but not the immediate-recall condition, Logical Memory generated more pronounced practice effects than NAB List Learning (b = 0.16, p < .01 for controls). These differential practice effects were moderated by clinical diagnosis, such that controls and MCI participants-but not participants with AD-improved more on Logical Memory delayed recall than on delayed NAB List Learning delayed recall over five annual assessments. Because the Logical Memory test is ubiquitous in cognitive aging and neurodegenerative disease research, its tendency to produce marked practice effects-especially on the delayed recall condition-suggests a threat to its validity as a measure of new learning, an essential construct for dementia diagnosis.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0164492PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5053775PMC
June 2017

Sizanani: A Randomized Trial of Health System Navigators to Improve Linkage to HIV and TB Care in South Africa.

J Acquir Immune Defic Syndr 2016 Oct;73(2):154-60

Divisions of *Infectious Diseases;†General Medicine, Massachusetts General Hospital, Boston, MA;‡Medical Practice Evaluation Center, Massachusetts General Hospital, Boston, MA;§Harvard Medical School, Boston, MA;‖Harvard University Center for AIDS Research, Harvard University, Boston, MA;¶Data Coordinating Center, Boston University School of Public Health, Boston, MA;#McCord Hospital, Durban, South Africa;**Division of General Pediatrics, Department of Medicine, Boston Children's Hospital, Boston, MA;††St. Mary's Hospital, Durban, South Africa;‡‡Department of Epidemiology, Boston University School of Public Health, Boston, MA;§§Department of Health Policy and Management, Harvard School of Public Health, Boston, MA;Divisions of ‖‖Rheumatology;¶¶Infectious Diseases, Brigham and Women's Hospital, Boston, MA;##Department of Orthopedic Surgery, Brigham and Women's Hospital, Boston, MA; and***Department of Biostatistics, Boston University School of Public Health, Boston, MA.

Background: A fraction of HIV-diagnosed individuals promptly initiate antiretroviral therapy (ART). We evaluated the efficacy of health system navigators for improving linkage to HIV and tuberculosis (TB) care among newly diagnosed HIV-infected outpatients in Durban, South Africa.

Methods: We conducted a randomized controlled trial (Sizanani Trial, NCT01188941) among adults (≥18 years) at 4 sites. Participants underwent TB screening and randomization into a health system navigator intervention or usual care. Intervention participants had an in-person interview at enrollment and received phone calls and text messages over 4 months. We assessed 9-month outcomes via medical records and the National Population Registry. Primary outcome was completion of at least 3 months of ART or 6 months of TB treatment for coinfected participants.

Results: Four thousand nine hundred three participants were enrolled and randomized; 1899 (39%) were HIV-infected, with 1146 (60%) ART-eligible and 523 (28%) TB coinfected at baseline. In the intervention, 212 (39% of outcome-eligible) reached primary outcome compared to 197 (42%) in usual care (RR 0.93, 95% CI: 0.80 to 1.08). One hundred thirty-one (14%) HIV-infected intervention participants died compared to 119 (13%) in usual care; death rates did not differ between arms (RR 1.06, 95% CI: 0.84 to 1.34). In the as-treated analysis, participants reached for ≥5 navigator calls were more likely to achieve study outcome.

Conclusions: ∼40% of ART-eligible participants in both study arms reached the primary outcome 9 months after HIV diagnosis. Low rates of engagement in care, high death rates, and lack of navigator efficacy highlight the urgency of identifying more effective strategies for improving HIV and TB care outcomes.
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http://dx.doi.org/10.1097/QAI.0000000000001025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5026386PMC
October 2016

Olfactory Function and Associated Clinical Correlates in Former National Football League Players.

J Neurotrauma 2017 02 11;34(4):772-780. Epub 2016 Aug 11.

1 Department of Neurology, Boston University Alzheimer's Disease and CTE Center, Boston University School of Medicine , Boston, Massachusetts.

Professional American football players incur thousands of repetitive head impacts (RHIs) throughout their lifetime. The long-term consequences of RHI are not well characterized, but may include olfactory dysfunction. RHI has been associated with changes to brain regions involved in olfaction, and olfactory impairment is common after traumatic brain injury. Olfactory dysfunction is a frequent early sequelae of neurodegenerative diseases (e.g., Alzheimer's disease), and RHI is associated with the neurodegenerative disease, chronic traumatic encephalopathy (CTE). We examined olfaction, and its association with clinical measures, in former National Football League (NFL) players. Ninety-five former NFL players (ages 40-69) and 28 same-age controls completed a neuropsychological and neuropsychiatric evaluation as part of a National Institutes of Health-funded study. The Brief Smell Identification Test (B-SIT) assessed olfaction. Principal component analysis generated a four-factor structure of the clinical measures: behavioral/mood, psychomotor speed/executive function, and verbal and visual memory. Former NFL players had worse B-SIT scores relative to controls (p = 0.0096). A B-SIT cutoff of 11 had the greatest accuracy (c-statistic = 0.61) and specificity (79%) for discriminating former NFL players from controls. In the former NFL players, lower B-SIT scores correlated with greater behavioral/mood impairment (p = 0.0254) and worse psychomotor speed/executive functioning (p = 0.0464) after controlling for age and education. Former NFL players exhibited lower olfactory test scores relative to controls, and poorer olfactory test performance was associated with worse neuropsychological and neuropsychiatric functioning. Future work that uses more-comprehensive tests of olfaction and structural and functioning neuroimaging may improve understanding on the association between RHI and olfaction.
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http://dx.doi.org/10.1089/neu.2016.4536DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5314992PMC
February 2017

Screening Utility of the King-Devick Test in Mild Cognitive Impairment and Alzheimer Disease Dementia.

Alzheimer Dis Assoc Disord 2017 Apr-Jun;31(2):152-158

*Department of Neurology, Brigham and Women's Hospital †Department of Neurology, Massachusetts General Hospital, Harvard Medical School ‡Boston University Alzheimer's Disease and CTE Center Departments of ∥Neurology ¶Pathology and Laboratory Medicine ‡‡Neurosurgery and Anatomy & Neurobiology, Boston University School of Medicine §Data Coordinating Center **Department of Biostatistics, Boston University School of Public Health #VA Boston Healthcare System, Boston, MA ††Departments of Neurology, Population Health and Ophthalmology, New York University School of Medicine, New York, NY.

The King-Devick (K-D) test is a 1 to 2 minute, rapid number naming test, often used to assist with detection of concussion, but also has clinical utility in other neurological conditions (eg, Parkinson disease). The K-D involves saccadic eye and other eye movements, and abnormalities thereof may be an early indicator of Alzheimer disease (AD)-associated cognitive impairment. No study has tested the utility of the K-D in AD and we sought to do so. The sample included 206 [135 controls, 39 mild cognitive impairment (MCI), and 32 AD dementia] consecutive subjects from the Boston University Alzheimer's Disease Center registry undergoing their initial annual evaluation between March 2013 and July 2015. The K-D was administered during this period. Areas under the receiver operating characteristic curves generated from logistic regression models revealed the K-D test distinguished controls from subjects with cognitive impairment (MCI and AD dementia) [area under the curve (AUC)=0.72], MCI (AUC=0.71) and AD dementia (AUC=0.74). K-D time scores between 48 and 52 seconds were associated with high sensitivity (>90.0%) and negative predictive values (>85.0%) for each diagnostic group. The K-D correlated strongly with validated attention, processing speed, and visual scanning tests. The K-D test may be a rapid and simple effective screening tool to detect cognitive impairment associated with AD.
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http://dx.doi.org/10.1097/WAD.0000000000000157DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5154783PMC
December 2017

Linking Infectious and Narcology Care (LINC) in Russia: design, intervention and implementation protocol.

Addict Sci Clin Pract 2016 May 4;11(1):10. Epub 2016 May 4.

Clinical Addiction Research and Education (CARE) Unit, Department of Medicine, Section of General Internal Medicine, Boston University School of Medicine/Boston Medical Center, 801 Massachusetts Avenue, 2nd Floor, Boston, MA, 02118, USA.

Background: Russia and Eastern Europe have one of the fastest growing HIV epidemics in the world. While countries in this region have implemented HIV testing within addiction treatment systems, linkage to HIV care from these settings is not yet standard practice. The Linking Infectious and Narcology Care (LINC) intervention utilized peer-led strengths-based case management to motivate HIV-infected patients in addiction treatment to obtain HIV care. This paper describes the protocol of a randomized controlled trial evaluating the effectiveness of the LINC intervention in St. Petersburg, Russia.

Methods/design: Participants (n = 349) were recruited from the inpatient wards at the City Addiction Hospital in St. Petersburg, Russia. After completing a baseline assessment, participants were randomly assigned to receive either the LINC intervention or standard of care. Participants returned for research assessments 6 and 12 months post-baseline. Primary outcomes were assessed via chart review at HIV treatment locations.

Discussion: LINC holds the potential to offer an effective approach to coordinating HIV care for people who inject drugs in Russia. The LINC intervention utilizes existing systems of care in Russia, minimizing adoption of substantial infrastructure for implementation. Trial Registration NCT01612455.
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http://dx.doi.org/10.1186/s13722-016-0058-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4855723PMC
May 2016

Cumulative Head Impact Exposure Predicts Later-Life Depression, Apathy, Executive Dysfunction, and Cognitive Impairment in Former High School and College Football Players.

J Neurotrauma 2017 01 15;34(2):328-340. Epub 2016 Jun 15.

1 Boston University Alzheimer's Disease and CTE Center, Boston University School of Medicine , Boston, Massachusetts.

The term "repetitive head impacts" (RHI) refers to the cumulative exposure to concussive and subconcussive events. Although RHI are believed to increase risk for later-life neurological consequences (including chronic traumatic encephalopathy), quantitative analysis of this relationship has not yet been examined because of the lack of validated tools to quantify lifetime RHI exposure. The objectives of this study were: 1) to develop a metric to quantify cumulative RHI exposure from football, which we term the "cumulative head impact index" (CHII); 2) to use the CHII to examine the association between RHI exposure and long-term clinical outcomes; and 3) to evaluate its predictive properties relative to other exposure metrics (i.e., duration of play, age of first exposure, concussion history). Participants included 93 former high school and collegiate football players who completed objective cognitive and self-reported behavioral/mood tests as part of a larger ongoing longitudinal study. Using established cutoff scores, we transformed continuous outcomes into dichotomous variables (normal vs. impaired). The CHII was computed for each participant and derived from a combination of self-reported athletic history (i.e., number of seasons, position[s], levels played), and impact frequencies reported in helmet accelerometer studies. A bivariate probit, instrumental variable model revealed a threshold dose-response relationship between the CHII and risk for later-life cognitive impairment (p < 0.0001), self-reported executive dysfunction (p < 0.0001), depression (p < 0.0001), apathy (p = 0.0161), and behavioral dysregulation (p < 0.0001). Ultimately, the CHII demonstrated greater predictive validity than other individual exposure metrics.
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http://dx.doi.org/10.1089/neu.2016.4413DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5220530PMC
January 2017

HERMITAGE--a randomized controlled trial to reduce sexually transmitted infections and HIV risk behaviors among HIV-infected Russian drinkers.

Addiction 2015 Jan 16;110(1):80-90. Epub 2014 Oct 16.

Department of Medicine, Section of General Internal Medicine, Clinical Addiction Research and Education (CARE) Unit, Boston University School of Medicine/Boston Medical Center, Boston, MA, USA; Department of Community Health Sciences, Boston University School of Public Health, Boston, MA, USA.

Aims: This study assessed the effectiveness of HERMITAGE (HIV's Evolution in Russia-Mitigating Infection Transmission and Alcoholism in a Growing Epidemic), an adapted secondary HIV prevention intervention, compared with an attention control condition in decreasing sexually transmitted infections (STIs) and sex and drug risk behaviors among Russian HIV-infected heavy drinkers.

Design: We conducted a single-blinded, two-armed, randomized controlled trial with 12-month follow-up.

Setting: The study was conducted in St Petersburg, Russia. Participants were recruited from four HIV and addiction clinical sites. The intervention was conducted at Botkin Infectious Disease Hospital.

Participants: HIV-infected individuals with past 6-month risky sex and heavy alcohol consumption (n = 700) were randomized to the HERMITAGE intervention (n = 350) or an attention control condition (n = 350).

Intervention: A Healthy Relationships Intervention stressing disclosure of HIV serostatus and condom use, adapted for a Russian clinical setting with two individual sessions and three small group sessions.

Measurements: The primary outcome was incident STI by laboratory test at 12-month follow-up. Secondary outcomes included change in unprotected sex and several alcohol and injection drug use (IDU) variables.

Findings: Participants had the following baseline characteristics: 59.3% male, mean age 30.1, 60.4% past year IDU, 15.4% prevalent STI and mean CD4 cell count 413.3/μl. Assessment occurred among 75 and 71% of participants at 6 and 12 months, respectively. STIs occurred in 20 subjects (8.1%) in the intervention group and 28 subjects (12.0%) in the control group at 12-month follow-up; logistic regression analyses found no significant difference between groups (adjusted odds ratio 0.63; 95% confidence interval = 0.34-1.18; P = 0.15). Both groups decreased unsafe behaviors, although no significant differences were found between groups.

Conclusions: The HERMITAGE HIV risk reduction intervention does not appear to reduce sexually transmitted infections and HIV risk behaviors in Russian HIV-infected heavy drinkers compared with attention controls.
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http://dx.doi.org/10.1111/add.12716DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4270840PMC
January 2015

Screening and brief intervention for drug use in primary care: the ASPIRE randomized clinical trial.

JAMA 2014 Aug;312(5):502-13

Department of Community Health Sciences, Boston University School of Public Health, Boston, Massachusetts2Clinical Addiction Research and Education (CARE) Unit, Section of General Internal Medicine, Department of Medicine, Boston Medical Center and Boston.

Importance: The United States has invested substantially in screening and brief intervention for illicit drug use and prescription drug misuse, based in part on evidence of efficacy for unhealthy alcohol use. However, it is not a recommended universal preventive service in primary care because of lack of evidence of efficacy.

Objective: To test the efficacy of 2 brief counseling interventions for unhealthy drug use (any illicit drug use or prescription drug misuse)-a brief negotiated interview (BNI) and an adaptation of motivational interviewing (MOTIV)-compared with no brief intervention.

Design, Setting, And Participants: This 3-group randomized trial took place at an urban hospital-based primary care internal medicine practice; 528 adult primary care patients with drug use (Alcohol, Smoking, and Substance Involvement Screening Test [ASSIST] substance-specific scores of ≥4) were identified by screening between June 2009 and January 2012 in Boston, Massachusetts.

Interventions: Two interventions were tested: the BNI is a 10- to 15-minute structured interview conducted by health educators; the MOTIV is a 30- to 45-minute intervention based on motivational interviewing with a 20- to 30-minute booster conducted by master's-level counselors. All study participants received a written list of substance use disorder treatment and mutual help resources.

Main Outcomes And Measures: Primary outcome was number of days of use in the past 30 days of the self-identified main drug as determined by a validated calendar method at 6 months. Secondary outcomes included other self-reported measures of drug use, drug use according to hair testing, ASSIST scores (severity), drug use consequences, unsafe sex, mutual help meeting attendance, and health care utilization.

Results: At baseline, 63% of participants reported their main drug was marijuana, 19% cocaine, and 17% opioids. At 6 months, 98% completed follow-up. Mean adjusted number of days using the main drug at 6 months was 12 for no brief intervention vs 11 for the BNI group (incidence rate ratio [IRR], 0.97; 95% CI, 0.77-1.22) and 12 for the MOTIV group (IRR, 1.05; 95% CI, 0.84-1.32; P = .81 for both comparisons vs no brief intervention). There were also no significant effects of BNI or MOTIV on any other outcome or in analyses stratified by main drug or drug use severity.

Conclusions And Relevance: Brief intervention did not have efficacy for decreasing unhealthy drug use in primary care patients identified by screening. These results do not support widespread implementation of illicit drug use and prescription drug misuse screening and brief intervention.

Trial Registration: clinicaltrials.gov Identifier: NCT00876941.
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http://dx.doi.org/10.1001/jama.2014.7862DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4667772PMC
August 2014

Risk factors for recent nonfatal overdose among HIV-infected Russians who inject drugs.

AIDS Care 2014 2;26(8):1013-8. Epub 2014 Jan 2.

a Clinical Addiction Research and Education Unit, Section of General Internal Medicine , Boston University School of Medicine, Boston Medical Center , Boston , MA , USA.

Overdoses and HIV infection are common among Russians who inject drugs, yet risk factors have not been studied. We analyzed baseline data of 294 participants with 30-day injection drug use from an HIV secondary prevention trial for persons reporting "heavy" alcohol use (National Institute on Alcohol Abuse and Alcoholism [NIAAA] risky drinking definition) and risky sex in the past 6 months. The outcome was any self-reported overdose in the previous 3 months. We examined demographic, HIV-related, criminal justice, mental health, substance use, and injection risk factors. Participants' characteristics included median age 29 years, 117/294 (40%) female, and median CD4 cell count 345/µl. Over three quarters 223/294 (76%) reported a history of overdose and 47/294 (16%) reported overdose in the past 3 months. Past month injection frequency (adjusted odds ratio [AOR] 4.77, 95% confidence interval [CI]: 1.63-14.0 highest vs. lowest quartile; AOR 3.58, 95% CI: 1.20-10.69 second highest vs. lowest quartile) and anti-retroviral therapy (ART) at time of interview (AOR 3.96 95% CI: 1.33-11.83) were associated with 3-month overdose. Nonfatal overdose among HIV-infected Russians who inject drugs is common. Risk factors include injection frequency and anti-retroviral therapy (ART), which warrant further study. Overdose prevention efforts are needed among HIV-infected Russians who inject drugs.
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http://dx.doi.org/10.1080/09540121.2013.871218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4040021PMC
May 2015

Increased risk of recurrent gout attacks with hospitalization.

Am J Med 2013 Dec 18;126(12):1138-41.e1. Epub 2013 Sep 18.

Section of Rheumatology, Department of Medicine, Boston Medical Center, Boston, Mass. Electronic address:

Background: Although anecdotal evidence suggests that the risk of recurrent gout attack increases with hospitalization, no study has formally tested this hypothesis.

Methods: We conducted an online case-crossover study of individuals with gout. We obtained information on gout attacks over a 1-year period, including onset date, symptoms and signs, medications, and exposure to potential risk factors, including hospitalization, during the 2-day hazard period before each gout attack. The same exposure information also was obtained over 2-day intercritical gout control periods. We performed conditional logistic regression to examine the relationship of hospitalization with recurrent gout attacks and whether such a relationship was modified by concomitant use of anti-gout medications.

Results: Of 724 participants (mean age, 54.5 years; 78.5% male), 35 hospitalizations occurred during a hazard or control period. The adjusted odds of gout attacks was increased 4-fold with hospitalization (odds ratio, 4.05; 95% confidence interval, 1.78-9.19) compared with no hospitalization. The effect of hospitalization tended to attenuate with the use of allopurinol, colchicine, or nonsteroidal anti-inflammatory drugs, but not statistically significantly.

Conclusions: Our study confirmed that the risk of gout attacks increases among patients with gout during hospitalization. Appropriate measures should be considered for prevention of gout attacks during hospitalization for patients with preexisting gout.
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http://dx.doi.org/10.1016/j.amjmed.2013.06.026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3838663PMC
December 2013