Publications by authors named "June-Ho Kim"

23 Publications

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Predictors of patient-reported quality of care in low- and middle-income countries: a four-country survey of person-centered care.

Int J Qual Health Care 2021 Aug;33(3)

Ariadne Labs, Brigham and Women's Hospital & Harvard T.H. Chan School of Public Health, 401 Park Drive, 3rd Floor East, Boston, MA 02215, USA.

Background: Person-centeredness is a foundation of high-quality health systems but is poorly measured in low- and middle-income countries (LMICs). We piloted an online survey of four LMICs to identify the prevalence and correlates of excellent patient-reported quality of care (QOC).

Objective: The aims of this study were to investigate the examine people's overall ratings of care quality in relation to their experiences seeking care in their respective health systems as well as individual-, provider- and facility-level predictors.

Methods: We administered a cross-sectional online survey using Random Domain Intercept Technology to collect a sample of random internet users across India, Kenya, Mexico and Nigeria in November 2016. The primary outcome was patient-reported QOC. Covariates included age, gender, level of education, urban/rural residence, person for whom care was sought, type of provider seen, public or private sector status of the health facility and type of facility. The exposure was an index of health system responsiveness based on a framework from the World Health Organization. We used descriptive statistics to determine the prevalence of excellent patient-reported QOC and multivariable Poisson regression to calculate adjusted prevalence ratios (aPRs) for predictors of excellent patient-reported quality.

Results: Fourteen thousand and eight people completed the survey (22.6% completion rate). Survey respondents tended to be young, male, well-educated and urban-dwelling, reflective of the demographic of the internet-using population. Four thousand one and ninety-one (29.9%) respondents sought care in the prior 6 months. Of those, 21.8% rated their QOC as excellent. The highest proportion of respondents gave the top rating for wait time (44.6%), while the lowest proportion gave the top rating for facility cleanliness (21.7%). In an adjusted analysis, people who experienced the highest level of health system responsiveness were significantly more likely to report excellent QOC compared to those who did not (aPR 8.61, 95% confidence interval [95% CI]: 7.50, 9.89). In the adjusted model, urban-dwelling individuals were less likely to report excellent quality compared to rural-dwelling individuals (aPR 0.88, 95% CI: 0.78, 0.99). People who saw community health workers (aPR 1.37, 95% CI: 1.12, 1.67) and specialists (aPR 1.30, 95% CI: 1.12, 1.50) were more likely to report excellent quality than those who saw primary care providers. High perceived respect from the provider or staff was most highly associated with excellent ratings of quality, while ratings of wait time corresponded the least.

Conclusion: Patient-reported QOC is low in four LMICs, even among a well-educated, young population of internet users. Better health system responsiveness may be associated with better ratings of care quality. Improving person-centered care will be an important component of building high-quality health systems in these LMICs.
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http://dx.doi.org/10.1093/intqhc/mzab110DOI Listing
August 2021

Does decentralization of health systems translate into decentralization of authority? A decision space analysis of Ugandan healthcare facilities.

Health Policy Plan 2021 Jun 24. Epub 2021 Jun 24.

Northwestern University Feinberg School of Medicine, 420 East Superior Street, Chicago, IL 60611, USA.

Since the 1990s, following similar reforms to its general politico-administrative systems, Uganda has decentralized its public healthcare system by shifting decision-making power away from its central Ministry of Health and towards more distal administrative levels. Previous research has used decision space-the decision-making autonomy demonstrated by entities in an administrative hierarchy-to measure overall health system decentralization. This study aimed to determine how the decision-making autonomy reported by managers of Ugandan healthcare facilities (de facto decision space) differs from that which they are allocated by official policies (de jure decision space). Additionally, it sought to determine associations between decision space and indicators of managerial performance. Using quantitative primary healthcare data from Ugandan healthcare facilities, our study determined the decision space expressed by facility managers and the performance of their facilities on measures of essential drug availability, quality improvement and performance management. We found managers reported greater facility-level autonomy than expected in disciplining staff compared with recruitment and promotion, suggesting that managerial functions that require less financial or logistical investment (i.e. discipline) may be more susceptible to differences in de jure and de facto decision space than those that necessitate greater investment (i.e. recruitment and promotion). Additionally, we found larger public health facilities expressed significantly greater facility-level autonomy in drug ordering compared with smaller facilities, which indicates ongoing changes in the Ugandan medical supply chain to a hybrid 'push-pull' system. Finally, we found increased decision space was significantly positively associated with some managerial performance indicators, such as essential drug availability, but not others, such as our performance management and quality improvement measures. We conclude that increasing managerial autonomy alone is not sufficient for improving overall health facility performance and that many factors, specific to individual managerial functions, mediate relationships between decision space and performance.
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http://dx.doi.org/10.1093/heapol/czab074DOI Listing
June 2021

Treated HIV Infection and Progression of Carotid Atherosclerosis in Rural Uganda: A Prospective Observational Cohort Study.

J Am Heart Assoc 2021 Jun 5;10(12):e019994. Epub 2021 Jun 5.

Faculty of Medicine Mbarara University of Science and Technology Mbarara Uganda.

Background Although ≈70% of the world's population of people living with HIV reside in sub-Saharan Africa, there are minimal prospective data on the contributions of HIV infection to atherosclerosis in the region. Methods and Results We conducted a prospective observational cohort study of people living with HIV on antiretroviral therapy >40 years of age in rural Uganda, along with population-based comparators not infected with HIV. We collected data on cardiovascular disease risk factors and carotid ultrasound measurements annually. We fitted linear mixed effects models, adjusted for cardiovascular disease risk factors, to estimate the association between HIV serostatus and progression of carotid intima media thickness (cIMT). We enrolled 155 people living with HIV and 154 individuals not infected with HIV and collected cIMT images at 1045 visits during a median of 4 annual visits per participant (interquartile range 3-4, range 1-5). Age (median 50.9 years) and sex (49% female) were similar by HIV serostatus. At enrollment, there was no difference in mean cIMT by HIV serostatus (0.665 versus 0.680 mm, =0.15). In multivariable models, increasing age, blood pressure, and non-high-density lipoprotein cholesterol were associated with greater cIMT (<0.05), however change in cIMT per year was also no different by HIV serostatus (0.004 mm/year for HIV negative [95% CI, 0.001-0.007 mm], 0.006 mm/year for people living with HIV [95% CI, 0.003-0.008 mm], HIV×time interaction =0.25). Conclusions In rural Uganda, treated HIV infection was not associated with faster cIMT progression. These results do not support classification of treated HIV infection as a risk factor for subclinical atherosclerosis progression in rural sub-Saharan Africa. Registration URL: https://www.ClinicalTrials.gov; Unique identifier: NCT02445079.
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http://dx.doi.org/10.1161/JAHA.120.019994DOI Listing
June 2021

Pandemic preparedness of an academic medical centre in the Republic of Korea.

Clin Microbiol Infect 2020 Dec 3;26(12):1595-1599. Epub 2020 Sep 3.

Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Gyeonggi-do, Republic of Korea.

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http://dx.doi.org/10.1016/j.cmi.2020.08.032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7470819PMC
December 2020

Assessment of Bypass of the Nearest Primary Health Care Facility Among Women in Ghana.

JAMA Netw Open 2020 08 3;3(8):e2012552. Epub 2020 Aug 3.

Ariadne Labs, Brigham and Women's Hospital, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.

Importance: Recent reports have highlighted that expanding access to health care is ineffective at meeting the goal of universal health coverage if the care offered does not meet a minimum level of quality. Health care facilities nearest to patient's homes that are perceived to offer inadequate or inappropriate care are frequently bypassed in favor of more distant private or tertiary-level hospital facilities that are perceived to offer higher-quality care.

Objective: To estimate the frequency with which women in Ghana bypass the nearest primary health care facility and describe patient experiences, costs, and other factors associated with this choice.

Design, Setting, And Participants: This nationally representative survey study was conducted in 2017 and included 4203 households to identify women in Ghana aged 15 to 49 years (ie, reproductive age) who sought primary care within the last 6 months. Women who sought care within the past 6 months were included in the study. Data were analyzed from 2018 to 2019.

Exposures: Bypass was defined as a woman's report that she sought care at a health facility other than the nearest facility.

Main Outcomes And Measures: Sociodemographic characteristics, reasons why women sought care, reasons why women bypassed their nearest facility, ratings for responsiveness of care, patient experience, and out-of-pocket costs. All numbers and percentages were survey-weighted to account for survey design.

Results: A total of 4289 women met initial eligibility criteria, and 4207 women (98.1%) completed the interview. A total of 1993 women reported having sough health care in the past 6 months, and after excluding those who were ineligible and survey weighting, the total sample included 1946 women. Among these, 629 women (32.3%) reported bypassing their nearest facilities for primary care. Women who bypassed their nearest facilities, compared with women who did not, were more likely to visit a private facility (152 women [24.5%] vs 202 women [15.6%]) and borrow money to pay for their care (151 women [24.0%] vs 234 women [17.8%]). After adjusting for covariates, women who bypassed reported paying a mean of 107.2 (95% CI, 79.1-135.4) Ghanaian Cedis (US $18.50 [95% CI, $13.65-$23.36]) for their care, compared with a mean of 58.6 (95% CI, 28.1-89.2) Ghanaian Cedis (US $10.11 [95% CI, $4.85-15.35]) for women who did not bypass (P = .006). Women who bypassed cited clinician competence (136 women [34.3%]) and availability of supplies (93 women [23.4%]) as the most important factors in choosing a health facility.

Conclusions And Relevance: The findings of this survey study suggest that bypassing the nearest health care facility was common among women in Ghana and that available services at lower levels of primary care are not meeting the needs of a large proportion of women. Among the benefits women perceived from bypassing were clinician competence and availability of supplies. These data provide insights to policy makers regarding potential gaps in service delivery and may help to guide primary health care improvement efforts.
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http://dx.doi.org/10.1001/jamanetworkopen.2020.12552DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7424402PMC
August 2020

Disparities in United States hospitalizations for serious infections in patients with and without opioid use disorder: A nationwide observational study.

PLoS Med 2020 08 7;17(8):e1003247. Epub 2020 Aug 7.

Harvard Medical School, Boston, Massachusetts, United States of America.

Background: Patients with opioid use disorder (OUD) who are hospitalized for serious infections requiring prolonged intravenous antibiotics may face barriers to discharge, which could prolong hospital length of stay (LOS) and increase financial burden. We investigated differences in LOS, discharge disposition, and charges between hospitalizations for serious infections in patients with and without OUD.

Methods And Findings: We utilized the 2016 National Inpatient Sample-a nationally representative database of all discharges from US acute care hospitals. The population of interest was all hospitalizations for infective endocarditis, epidural abscess, septic arthritis, or osteomyelitis. The exposure was OUD, and the primary outcome was LOS until discharge, assessed by using a competing risks analysis to estimate adjusted hazard ratios (aHRs). Adjusted odds ratio (aOR) of discharge disposition and adjusted differences in hospital charges were also reported. Of 95,470 estimated hospitalizations for serious infections (infective endocarditis, epidural abscess, septic arthritis, and osteomyelitis), the mean age was 49 years and 35% were female. 46% had Medicare (government-based insurance coverage for people age 65+ years), and 70% were non-Hispanic white. After adjustment for potential confounders, OUD was associated with a lower probability of discharge at any given LOS (aHR 0.61; 95% CI 0.59-0.63; p < 0.001). OUD was also associated with lower odds of discharge to home (aOR 0.38; 95% CI 0.33-0.43; p < 0.001) and higher odds of discharge to a post-acute care facility (aOR 1.85; 95% CI 1.57-2.17; p < 0.001) or patient-directed discharge (also referred to as "discharge against medical advice") (aOR 3.47; 95% CI 2.80-4.29; p < 0.001). There was no significant difference in average total hospital charges, though daily hospital charges were significantly lower for patients with OUD. Limitations include the potential for unmeasured confounders and the use of billing codes to identify cohorts.

Conclusions: Our findings suggest that among hospitalizations for some serious infections, those involving patients with OUD were associated with longer LOS, higher odds of discharge to post-acute care facilities or patient-directed discharge, and similar total hospital charges, despite lower daily charges. These findings highlight opportunities to improve care for patients with OUD hospitalized with serious infections, and to reduce the growing associated costs.
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http://dx.doi.org/10.1371/journal.pmed.1003247DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7413412PMC
August 2020

Against medical advice discharges in injection and non-injection drug use-associated infective endocarditis: A nationwide cohort study.

Clin Infect Dis 2020 Aug 5. Epub 2020 Aug 5.

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

Background: Among those with injection drug use-associated infective endocarditis (IDU-IE), against medical advice (AMA) discharge is common and linked to adverse outcomes. Understanding trends, risk factors and timing is needed to reduce IDU-IE AMA discharges.

Methods: We identified individuals ages 18-64 with International Classification of Diseases, 9thRevision diagnosis codes for infective endocarditis (IE) in the National Inpatient Sample, a representative sample of United States hospitalizations from January 2010 to September 2015. We plotted unadjusted quarter-year trends for AMA discharges and used multivariable logistic regression to identify factors associated with AMA discharge among IE hospitalizations, comparing IDU-IE to non-IDU-IE.

Results: We identified 7,259 IDU-IE and 23,633 non-IDU-IE hospitalizations. Of these hospitalizations, 14.2% of IDU-IE and 1.9% of non-IDU-IE resulted in AMA discharges. More than 30% of AMA discharges for both groups occurred before hospital day 3. In adjusted models, IDU status [Adjusted Odds Ratio (AOR) 3.92 (95% CI: 3.43-4.48)] was associated with increased odds of AMA discharge. Among IDU-IE, women [AOR 1.21 (95% CI: 1.04-1.41)] and Hispanics [AOR 1.32 (95% CI: 1.03-1.69)] had increased odds of AMA discharge, which differed from non-IDU-IE. Over nearly 6-years, odds of AMA discharge increased 12% per year for IDU-IE [AOR 1.12 (95% CI: 1.07-1.18)] and 6% per year for non-IDU-IE [AOR 1.06 (95% CI: 1.00-1.13)].

Conclusion: AMA discharges have risen among individuals with IDU-IE and non-IDE-IE. Among those who inject drugs, AMA discharges were more common and increases sharper. Efforts that address the rising fraction, disparities, and timing of IDU-IE AMA discharges are needed.
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http://dx.doi.org/10.1093/cid/ciaa1126DOI Listing
August 2020

Towards patient-centred care in Ghana: health system responsiveness, self-rated health and experiential quality in a nationally representative survey.

BMJ Open Qual 2020 05;9(2)

Ariadne Labs, Brigham and Women's Hospital & Harvard T.H. Chan School of Public Health, Boston, Massachusetts, United States.

Introduction: Person-centredness, including patient experience and satisfaction, is a foundational element of quality of care. Evidence indicates that poor experience and satisfaction are drivers of underutilisation of healthcare services, which in turn is a major driver of avoidable mortality. However, there is limited information about patient experience of care at the population level, particularly in low-income and middle-income countries.

Methods: A multistage cluster sample design was used to obtain a nationally representative sample of women of reproductive age in Ghana. Women were interviewed in their homes regarding their demographic characteristics, recent care-seeking characteristics, satisfaction with care, patient-reported outcomes, and-using questions from the World Health Survey Responsiveness Module-the seven domains of responsiveness of outpatient care to assess patient experience. Using Poisson regression with log link, we assessed the relationship between responsiveness and satisfaction, as well as patient-reported outcomes.

Results: Women who reported more responsive care were more likely to be more educated, have good access to care and have received care at a private facility. Controlling for respondent and visit characteristics, women who reported the highest responsiveness levels were significantly more likely to report that care was excellent at meeting their needs (prevalence ratio (PR)=13.0), excellent quality of care (PR=20.8), being very likely to recommend the facility to others (PR=1.4), excellent self-rated health (PR=4.0) and excellent self-rated mental health (PR=5.1) as women who reported the lowest responsiveness levels.

Discussion: These findings support the emerging global consensus that responsiveness and patient experience of care are not luxuries but essential components of high-performing health systems, and highlight the need for more nuanced and systematic measurement of these areas to inform priority setting and improvement efforts.
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http://dx.doi.org/10.1136/bmjoq-2019-000886DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7228562PMC
May 2020

To fast or not to fast: Lipid measurement and cardiovascular disease risk estimation in rural sub-Saharan Africa.

J Glob Health 2020 Jun;10(1):010407

Harvard Medical School, Boston, Massachusetts, USA.

Background: Cardiovascular disease (CVD) morbidity and mortality are increasing in sub-Saharan Africa (sSA), highlighting the need for tools to enable CVD risk stratification in the region. Although non-HDL-cholesterol (nHDL-C) has been promoted as a method to measure lipids without a requirement for fasting in the USA, its diagnostic validity has not been assessed in sSA. We sought to estimate: 1) the association between LDL-cholesterol (LDL-C) and nHDL-C, 2) the impact of fasting on their measurement, and 3) their correlation with carotid atherosclerosis, within a rural Ugandan population with high HIV prevalence.

Methods: We collected traditional CVD risk factors, blood for serum lipid levels, self-reported fasting status, and performed carotid ultrasonography in 301 participants in rural Uganda. We fit regression models, stratified by fasting status, to estimate associations between carotid intima media thickness (cIMT), LDL-C, and nHDL-C.

Results: Median age was 50 years (interquartile range = 46-54), 49% were female, 51% were HIV-positive, and at the time of blood collection, 70% had fasted overnight. Mean LDL-C, nHDL-C, and triglycerides in the non-fasting and fasting groups were 85 vs 88 mg/dL ( = 0.39), 114 vs 114 mg/dL ( = 0.98), and 130 vs 114 mg/dL ( = 0.05) mg/dL, respectively. In unadjusted models, mean cIMT (mm) was associated with both increased LDL-C (β = 0.0078 per 10mg/dL,  < 0.01) and nHDL-C (β = 0.0075,  < 0.01), and these relationships were similar irrespective of fasting status. After adjustment for traditional CVD risk factors, we observed similar associations, albeit with muted effect sizes within the fasting group.

Conclusions: We found a high correlation between LDL-C and nHDL-C, and both were correlated with cIMT, irrespective of fasting or HIV serostatus in rural Uganda. Our findings support use of either fasting or non-fasting serum lipids for CVD risk estimation in rural sSA.
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http://dx.doi.org/10.7189/jogh.10.010407DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7101029PMC
June 2020

Identification of Racial Inequities in Access to Specialized Inpatient Heart Failure Care at an Academic Medical Center.

Circ Heart Fail 2019 11 29;12(11):e006214. Epub 2019 Oct 29.

Division of Cardiovascular Medicine, and Department of Medicine (E.F..L.), Brigham and Women's Hospital, Boston, MA.

Background: Racial inequities for patients with heart failure (HF) have been widely documented. HF patients who receive cardiology care during a hospital admission have better outcomes. It is unknown whether there are differences in admission to a cardiology or general medicine service by race. This study examined the relationship between race and admission service, and its effect on 30-day readmission and mortality Methods: We performed a retrospective cohort study from September 2008 to November 2017 at a single large urban academic referral center of all patients self-referred to the emergency department and admitted to either the cardiology or general medicine service with a principal diagnosis of HF, who self-identified as white, black, or Latinx. We used multivariable generalized estimating equation models to assess the relationship between race and admission to the cardiology service. We used Cox regression to assess the association between race, admission service, and 30-day readmission and mortality.

Results: Among 1967 unique patients (66.7% white, 23.6% black, and 9.7% Latinx), black and Latinx patients had lower rates of admission to the cardiology service than white patients (adjusted rate ratio, 0.91; 95% CI, 0.84-0.98, for black; adjusted rate ratio, 0.83; 95% CI, 0.72-0.97 for Latinx). Female sex and age >75 years were also independently associated with lower rates of admission to the cardiology service. Admission to the cardiology service was independently associated with decreased readmission within 30 days, independent of race.

Conclusions: Black and Latinx patients were less likely to be admitted to cardiology for HF care. This inequity may, in part, drive racial inequities in HF outcomes.
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http://dx.doi.org/10.1161/CIRCHEARTFAILURE.119.006214DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7183732PMC
November 2019

The status of Ghanaian community health workers' supervision and service delivery: descriptive analyses from the 2017 Performance Monitoring and Accountability 2020 survey.

Gates Open Res 2019 23;3:1468. Epub 2019 Aug 23.

Ariadne Labs, Brigham and Women's Hospital & Harvard T.H. Chan School of Public Health, Boston, MA, 02215, USA.

Community-based services are a critical component of high-quality primary healthcare. Ghana formally launched the National Community Health Worker (CHW) program in 2014, to augment the pre-existing Community-based Health Planning and Services (CHPS). To date, however, there is scant data about the program's implementation. We describe the current supervision and service delivery status of CHWs throughout the country. Data were collected regarding CHW supervision and service delivery during the 2017 round of the Performance Monitoring and Accountability 2020 survey. Descriptive analyses were performed by facility type, supervisor type, service delivery type, and regional distribution. Over 80% of CHWs had at least monthly supervision interactions, but there was variability in the frequency of interactions. Frequency of supervision interactions did not vary by facility or supervisor type. The types of services delivered by CHWs varied greatly by facility type and region. Community mobilization, health education, and outreach for loss-to-follow-up were delivered by over three quarters of CHWs, while mental health counseling and postnatal care are provided by fewer than one third of CHWs. The Western region and Greater Accra had especially low rates of CHW service provision. Non-communicable disease treatment, which is not included in the national guidelines, was reportedly provided by some CHWs in nine out of ten regions. Overall, this study demonstrates variability in supervision frequency and CHW activities. A high proportion of CHWs already meet the expected frequency of supervision. Meanwhile, there are substantial differences by region of CHW service provision, which requires further research, particularly on novel CHW services such as non-communicable disease treatment. While there are important limitations to these data, these findings can be instructive for Ghanaian policymakers and implementers to target improvement initiatives for community-based services.
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http://dx.doi.org/10.12688/gatesopenres.12979.3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6600081PMC
August 2019

Nonbacterial Thrombotic Endocarditis Due to Primary Gallbladder Malignancy with Recurrent Stroke Despite Anticoagulation: Case Report and Literature Review.

J Gen Intern Med 2019 09 16;34(9):1934-1940. Epub 2019 Jul 16.

Harvard Medical School, 25 Shattuck Street, Boston, MA, 02115, USA.

Nonbacterial thrombotic endocarditis (NBTE) associated with malignancy is rare; its infrequency and similarity to other diagnoses make it a significant diagnostic challenge. A 63-year-old woman on rivaroxaban for prior deep vein thrombosis presented with left upper extremity weakness and left facial droop with imaging demonstrating multiple strokes. Echocardiograms revealed mitral and aortic valve vegetations. The patient was switched to apixaban and started on vancomycin and ceftriaxone for presumed culture-negative endocarditis. Despite continuing apixaban, her hospital course was complicated by new acute embolic infarcts. Workup confirmed non-mucinous metastatic biliary adenocarcinoma. The patient was placed on a heparin drip then switched to low molecular weight heparin without further embolic events and was discharged to a rehabilitation facility in stable condition with plans for chemotherapy as an outpatient. These clinical, imaging, and histologic findings were consistent with a rare case of NBTE associated with primary non-mucinous gallbladder malignancy complicated by recurrent strokes in which direct oral anticoagulants did not provide adequate anticoagulation.
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http://dx.doi.org/10.1007/s11606-019-05166-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6712189PMC
September 2019

Blood pressure trajectories and the mediated effects of body mass index and HIV-related inflammation in a mixed cohort of people with and without HIV in rural Uganda.

J Clin Hypertens (Greenwich) 2019 08 6;21(8):1230-1241. Epub 2019 Jul 6.

Department of Internal Medicine, Mbarara University of Science and Technology, Mbarara, Uganda.

We sought to describe changes in blood pressure and estimate the effect of HIV on blood pressure (BP) over 4 years of observation in a cohort of 155 HIV-infected adults (≥40 years) on antiretroviral therapy (ART) and 154 sex- and age-quartile-matched, population-based, HIV-uninfected controls for four years in rural Uganda, we compared changes in blood pressure (BP) by HIV serostatus and tested whether body mass index and inflammation (high-sensitivity C-reactive protein and interleukin-6) and immune activation (sCD14 and sCD163) mediated the effects of HIV on BP using hierarchical multivariate and two-stage parametric regression models. Overall HIV-uninfected participants had higher mean BP than HIV-infected counterparts (differences in trend P < 0.0001 for diastolic BP and P = 0.164 for systolic BP). After initial declines in BP in both groups between years 1 and 2, BP moderately increased in both groups through year 4, with greater change over time observed in the HIV-uninfected group. Body mass index mediated 72% (95%CI 57, 97) of the association between HIV and systolic BP. We found a minimal mediating effect of sCD14 on the relationship between HIV and SBP (9%, 95% CI 5%, 21%), but found no association between other HIV-related biomarkers. Over four years of observation, HIV-infected people in rural Uganda have lower BP than HIV-uninfected counterparts despite having higher levels of inflammation. BMI, rather than measures of HIV-associated inflammation, explained a majority of the difference in BP observed.
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http://dx.doi.org/10.1111/jch.13621DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6759805PMC
August 2019

Distribution and Performance of Cardiovascular Risk Scores in a Mixed Population of HIV-Infected and Community-Based HIV-Uninfected Individuals in Uganda.

J Acquir Immune Defic Syndr 2018 08;78(4):458-464

Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA.

Background: The utility and validity of cardiovascular diseases (CVD) risk scores are not well studied in sub-Saharan Africa. We compared and correlated CVD risk scores with carotid intima media thickness (c-IMT) among HIV-infected and uninfected people in Uganda.

Methods: We first calculated CVD risk using the (1) Framingham laboratory-based score; (2) Framingham nonlaboratory score (FRS-BMI); (3) Reynolds risk score; (4) American College of Cardiology and American Heart Association score; and (5) the Data collection on Adverse Effects of Anti-HIV Drugs score. We then compared absolute risk scores and risk categories across each score using Pearson correlation and kappa statistics, respectively. Finally, we fit linear regression models to estimate the strength of association between each risk score and c-IMT.

Results: Of 205 participants, half were females and median age was 49 years [interquartile range (IQR) 46-53]. Median CD4 count was 430 cells/mm (IQR 334-546), with median 7 years of antiretroviral therapy exposure (IQR 6.4-7.5). HIV-uninfected participants had a higher median systolic blood pressure (121 vs. 110 mm Hg), prevalent current smokers (18% vs. 4%, P = 0.001), higher median CVD risk scores (P < 0.003), and greater c-IMT (0.68 vs. 0.63, P = 0.003). Overall, FRS-BMI was highly correlated with other risk scores (all rho >0.80). In linear regression models, we found significant correlations between increasing CVD risk and higher c-IMT (P < 0.01 in all models).

Conclusions: In this cross-sectional study from Uganda, the FRS-BMI correlated well with standard risk scores and c-IMT. HIV-uninfected individuals had higher risk scores than HIV-infected individuals, and the difference seemed to be driven by modifiable factors.
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http://dx.doi.org/10.1097/QAI.0000000000001696DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6019157PMC
August 2018

Ideal Cardiovascular Health and Carotid Atherosclerosis in a Mixed Cohort of HIV-Infected and Uninfected Ugandans.

AIDS Res Hum Retroviruses 2017 01 7;33(1):49-56. Epub 2016 Sep 7.

5 Center for Global Health , Massachusetts General Hospital, Boston, Massachusetts.

Preventable cardiovascular disease (CVD) risk factors are responsible for the majority of CVD-related deaths, and are increasingly recognized as a cause of morbidity and mortality for HIV-infected persons taking antiretroviral therapy (ART). Simplified tools such as the American Heart Association's ideal cardiovascular health (iCVH) construct may identify and prognosticate CVD risk in resource-limited settings. No studies have evaluated iCVH metrics in sub-Saharan Africa or among HIV-infected adults. Thus, the central aim of this study was to compare levels of iCVH metrics and their correlations with carotid atherosclerosis for HIV-infected adults versus uninfected controls in a well-phenotyped Ugandan cohort. We analyzed the prevalence of iCVH metrics in a mixed cohort of HIV-infected persons on stable ART and uninfected, population-based comparators in Mbarara, Uganda. We also assessed the validity of iCVH by correlating iCVH values with common carotid intima media thickness (CCIMT). HIV-infected persons had a mean of 4.9 (SD 1.1) iCVH metrics at ideal levels versus 4.3 (SD 1.2) for uninfected controls (p = .002). This difference was largely driven by differences in blood pressure, blood glucose, and diet. In multivariable-adjusted linear regression models, each additional iCVH metric at an ideal level was associated with a significant 0.024 mm decrease in CCIMT (p < .001).HIV-infected persons on ART in rural Uganda had more iCVH metrics at ideal levels than uninfected persons. The difference appeared driven by factors that are putatively influenced by access to routine medical care. Composite scores of iCVH metrics were associated with subclinical atherosclerosis and more predictive of atherosclerosis for uninfected persons.
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http://dx.doi.org/10.1089/AID.2016.0104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5240009PMC
January 2017

HIV infection and arterial stiffness among older-adults taking antiretroviral therapy in rural Uganda.

AIDS 2016 Feb;30(4):667-70

aDivision of Infectious Diseases, Department of Medicine, Massachusetts General Hospital bMassachusetts General Hospital Center for Global Health cHarvard Medical School dDepartment of Medicine, Brigham and Women's Hospital, Boston, MA, USA eFaculty of Internal Medicine, Mbarara University of Science and Technology, Mbarara, Uganda fDivision of Cardiology, Department of Medicine, Massachusetts General Hospital, Boston, MA gUniversity of California, San Francisco, CA, USA hEpicentre Research Base, Mbarara, Uganda iRagon Institute of MGH, MIT and Harvard, Boston, MA, USA jDepartment of Microbiology, Mbarara University of Science and Technology, Mbarara, Uganda.

HIV infection is associated with arterial stiffness, but no studies have assessed this relationship in sub-Saharan Africa. We enrolled 205 participants over 40 years old in Uganda: 105 on antiretroviral therapy for a median of 7 years, and a random sample of 100 age and sex-matched HIV-uninfected controls from the clinic catchment area. The prevalence of arterial stiffness (ankle brachial index  > 1.2) was 33%, 18%, 19% and 2% in HIV+ men, HIV- men, HIV+ women, and HIV- women. In multivariable models adjusted for cardiovascular risk factors, HIV+ individuals had over double the prevalence of arterial stiffness (adjusted prevalence ratio 2.86, 95% confidence interval 1.41-5.79, P = 0.003).
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http://dx.doi.org/10.1097/QAD.0000000000000992DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4733585PMC
February 2016

Persistent Immune Activation and Carotid Atherosclerosis in HIV-Infected Ugandans Receiving Antiretroviral Therapy.

J Infect Dis 2016 Feb 7;213(3):370-8. Epub 2015 Sep 7.

University of California, San Francisco.

Background: Human immunodeficiency virus (HIV) infection and associated immune activation predict the risk of cardiovascular disease in resource-rich areas. Less is known about these relationships in sub-Saharan Africa.

Methods: Beginning in 2005, we enrolled subjects in southwestern Uganda into a cohort at the time of antiretroviral therapy (ART) initiation. Multiple immune activation measures were assessed before and 6 months after ART initiation. Beginning in 2013, participants aged >40 years underwent metabolic profiling, including measurement of hemoglobin A1c and lipid levels and carotid ultrasonography. We fit regression models to identify traditional and HIV-specific correlates of common carotid intima media thickness (CCIMT).

Results: A total of 105 participants completed carotid ultrasonography, with a median completion time of 7 years following ART initiation. Age, low-density lipoprotein cholesterol level, and pre-ART HIV load were correlated with CCIMT. No association was found between CCIMT and any pre-ART biomarkers of immune activation. However, in multivariable models adjusted for cardiovascular disease risk factors, lower absolute levels of soluble CD14 and interleukin 6 and greater declines in the CD14 level and kynurenine-tryptophan ratio after 6 months of ART predicted a lower CCIMT years later (P < .01).

Conclusions: Persistent immune activation despite ART-mediated viral suppression predicts the future atherosclerotic burden among HIV-infected Ugandans. Future work should focus on clinical correlates of these relationships, to elucidate the long-term health priorities for HIV-infected people in the region.
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http://dx.doi.org/10.1093/infdis/jiv450DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4704672PMC
February 2016

Rare Cause of Recurrent Small-Bowel Obstruction.

JAMA Surg 2014 Jun;149(6):617-8

Department of Surgery, Johns Hopkins Bayview Medical Center, Baltimore, Maryland.

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http://dx.doi.org/10.1001/jamasurg.2013.2531DOI Listing
June 2014

Reducing false-positive biopsies: a pilot study to reduce benign biopsy rates for BI-RADS 4A/B assessments through testing risk stratification and new thresholds for intervention.

Breast Cancer Res Treat 2013 Jun 14;139(3):769-77. Epub 2013 Jun 14.

The aim of this study is to evaluate Breast Imaging Reporting and Data Systems (BI-RADS) 4A/B subcategory risk estimates for ductal carcinoma in situ (DCIS) and invasive cancer (IC), determining whether changing the proposed cutoffs to a higher biopsy threshold could safely increase cancer-to-biopsy yields while minimizing false-positive biopsies. A prospective clinical trial was performed to evaluate BI-RADS 4 lesions from women seen in clinic between January 2006 and March 2007. An experienced radiologist prospectively estimated a percent risk-estimate for DCIS and IC. Truth was determined by histopathology or 4-year follow-up negative for malignancy. Risk estimates were used to generate receiver-operating characteristic (ROC) curves. Biopsy rates, cancer-to-biopsy yields, and type of malignancies missed were then calculated across postulated risk thresholds. A total of 124 breast lesions were evaluated from 213 women. An experienced radiologist gave highly accurate risk estimates for IC, DCIS alone, or the combination with an area under ROC curve of 0.91 (95 % CI 0.84-0.99) (p < 0.001), 0.81 (95 % CI 0.69-0.93) (p = 0.011), and 0.89 (95 % CI 0.83-0.95) (p < 0.001), respectively. The cancer-to-biopsy yield was 30 %. Three hypothetical thresholds for intervention were analyzed: (1) DCIS or IC ≥ 10 %; (2) DCIS ≥ 50 % or IC ≥ 10 %; and (3) IC ≥ 10 %, which translated to 22, 48, and 56 % of biopsies avoided; cancer-to-biopsy yields of 36, 47, and 46 %; and associated chance of missing an IC of 0, 1, and 2 %, respectively. Expert radiologists estimate risk of IC and DCIS with a high degree of accuracy. Increasing the cut off point for recommending biopsy, substituting with a short-term follow-up protocol with biopsy if any change, may safely reduce the number of false-positive biopsies.
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http://dx.doi.org/10.1007/s10549-013-2576-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3695318PMC
June 2013

Diet and asthma: looking back, moving forward.

Respir Res 2009 Jun 12;10:49. Epub 2009 Jun 12.

Department of Cancer Immunology & AIDS, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.

Asthma is an increasing global health burden, especially in the western world. Public health interventions are sought to lessen its prevalence or severity, and diet and nutrition have been identified as potential factors. With rapid changes in diet being one of the hallmarks of westernization, nutrition may play a key role in affecting the complex genetics and developmental pathophysiology of asthma. The present review investigates hypotheses about hygiene, antioxidants, lipids and other nutrients, food types and dietary patterns, breastfeeding, probiotics and intestinal microbiota, vitamin D, maternal diet, and genetics. Early hypotheses analyzed population level trends and focused on major dietary factors such as antioxidants and lipids. More recently, larger dietary patterns beyond individual nutrients have been investigated such as obesity, fast foods, and the Mediterranean diet. Despite some promising hypotheses and findings, there has been no conclusive evidence about the role of specific nutrients, food types, or dietary patterns past early childhood on asthma prevalence. However, diet has been linked to the development of the fetus and child. Breastfeeding provides immunological protection when the infant's immune system is immature and a modest protective effect against wheeze in early childhood. Moreover, maternal diet may be a significant factor in the development of the fetal airway and immune system. As asthma is a complex disease of gene-environment interactions, maternal diet may play an epigenetic role in sensitizing fetal airways to respond abnormally to environmental insults. Recent hypotheses show promise in a biological approach in which the effects of dietary factors on individual physiology and immunology are analyzed before expansion into larger population studies. Thus, collaboration is required by various groups in studying this enigma from epidemiologists to geneticists to immunologists. It is now apparent that this multidisciplinary approach is required to move forward and understand the complexity of the interaction of dietary factors and asthma.
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http://dx.doi.org/10.1186/1465-9921-10-49DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2703624PMC
June 2009

Engagement of the type I interferon receptor on dendritic cells inhibits T helper 17 cell development: role of intracellular osteopontin.

Immunity 2008 Jul;29(1):68-78

Department of Cancer Immunology & AIDS, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA.

Mechanisms that prevent inappropriate or excessive interleukin-17-producing T helper (Th17) cell responses after microbial infection may be necessary to avoid autoimmunity. Here, we define a pathway initiated by engagement of type I IFN receptor (IFNAR) expressed by dendritic cells (DC) that culminated in suppression of Th17 cell differentiation. IFNAR-dependent inhibition of an intracellular translational isoform of Osteopontin, termed Opn-i, derepressed interleukin-27 (IL-27) secretion and prevented efficient Th17 responses. Moreover, Opn-i expression in DC and microglia regulated the type and intensity of experimental autoimmune encephalomyelitis (EAE). Mice containing DC deficient in Opn-i produced excessive amounts of IL-27 and developed a delayed disease characterized by an enhanced Th1 response compared with the dominant Th17 response of Opn-sufficient mice. Definition of the IFNAR-Opn-i axis that controls Th17 development provides insight into regulation of Th cell sublineage development and the molecular basis of type I interferon therapy for MS and other autoimmune diseases.
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http://dx.doi.org/10.1016/j.immuni.2008.05.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2625293PMC
July 2008

Alternative translation of osteopontin generates intracellular and secreted isoforms that mediate distinct biological activities in dendritic cells.

Proc Natl Acad Sci U S A 2008 May 14;105(20):7235-9. Epub 2008 May 14.

Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston MA 02115, USA.

Osteopontin (Opn) contributes to diverse biological processes that include immune responses, vascularization, and bone formation. Until recently, studies describing the activities of Opn have focused on the cytokine-like properties of the secreted protein. Here, we show that alternative translation of a single Opn mRNA species generates a secreted and intracellular isoform. Utilization of a 5' canonical translation start site generates a protein that includes an N-terminal signal sequence allowing targeting to secretory vesicles and cytokine secretion, whereas usage of a downstream start site generates a shortened protein that lacks the N-terminal signal sequence and localizes mainly to cytoplasm. The coordinated action of these Opn gene products regulates the functional phenotype of subsets of dendritic cells.
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http://dx.doi.org/10.1073/pnas.0802301105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2438233PMC
May 2008
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