Health and Medicine

FSI’s researchers assess health and medicine through the lenses of economics, nutrition and politics. They’re studying and influencing public health policies of local and national governments and the roles that corporations and nongovernmental organizations play in providing health care around the world. Scholars look at how governance affects citizens’ health, how children’s health care access affects the aging process and how to improve children’s health in Guatemala and rural China. They want to know what it will take for people to cook more safely and breathe more easily in developing countries.

FSI professors investigate how lifestyles affect health. What good does gardening do for older Americans? What are the benefits of eating organic food or growing genetically modified rice in China? They study cost-effectiveness by examining programs like those aimed at preventing the spread of tuberculosis in Russian prisons. Policies that impact obesity and undernutrition are examined; as are the public health implications of limiting salt in processed foods and the role of smoking among men who work in Chinese factories. FSI health research looks at sweeping domestic policies like the Affordable Care Act and the role of foreign aid in affecting the price of HIV drugs in Africa.

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Background: Pediatric liver transplant patients are at increased risk of post transplant lymphoproliferative disease (PTLD) from Epstein Barr virus (EBV) infection or reactivation after transplantation. The goal of this study was to determine the impact of induction and immunosuppression levels on the development of EBV viremia post transplantation. Methods: A retrospective chart review was performed on 104 patients less than 18 years of age who underwent isolated liver transplantation (LT) between 2000-2008 at Lucile Packard Children’s Hospital at Stanford University. Induction regiment, immunosuppression levels, and EBV viremia, as noted by any positive value of EBV polymerase chain reaction testing, was documented for one year post transplantation. Fixed-effects logistic regression models were constructed to determine associations between induction therapy, immunosuppression levels, and EBV viremia. A P-value < 0.05 was considered to be statistically significant. All statistical analyses were performed using STATA 11 (College Station, TX). Results: 56% of patients developed EBV viremia within one year of LT. Patients were more likely develop EBV viremia if they had received either anti-thymocyte globulin [ATG (73%)] or daclizumab (63%) for induction versus neither (39%), though the trend was not statistically significant (ATG: Odds ratio (OR) 0.19; 95% CI 0.024 – 1.58; p = 0.125; daclizumab: OR: 1.07; 95% CI 0.270 – 4.23; p=0.925). Tacrolimus immunosuppression levels were supratherapeutic 37% of the time within the first three months of transplant; however, only supratherapeutic tacrolimus levels between 0-2 weeks after transplant impacted the development of EBV viremia at 2-4 weeks post LT (OR 1.80; 95% CI 1.10-2.94; p=0.02). Only one patient developed PTLD during the study period. Conclusion: The type of induction used in isolated pediatric LT may play a role in the development of EBV viremia, with ATG and daclizumab leading to a higher incidence of EBV viremia, though it was not statistically significant. Supratherapeutic immunosuppression tacrolimus levels 0-2 weeks post LT impacted the development of EBV viremia at 2-4 weeks, but the effect was not seen at other time intervals. The incidence of PTLD in our study was low, suggesting better EBV and immunosuppression monitoring has played an important role in the reduction of complications associated with EBV viremia post pediatric LT.

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Journal Articles
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Transplantation Proceedings
Authors
KT Park
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Context  The effect of global health initiatives on population health is uncertain. Between 2003 and 2008, the US President's Emergency Plan for AIDS Relief (PEPFAR), the largest initiative ever devoted to a single disease, operated intensively in 12 African focus countries. The initiative's effect on all-cause adult mortality is unknown.

Objective  To determine whether PEPFAR was associated with relative changes in adult mortality in the countries and districts where it operated most intensively.

Design, Setting, and Participants  Using person-level data from the Demographic and Health Surveys, we conducted cross-country and within-country analyses of adult mortality (annual probability of death per 1000 adults between 15 and 59 years old) and PEPFAR's activities. Across countries, we compared adult mortality in 9 African focus countries (Ethiopia, Kenya, Mozambique, Namibia, Nigeria, Rwanda, Tanzania, Uganda, and Zambia) with 18 African nonfocus countries from 1998 to 2008. We performed subnational analyses using information on PEPFAR's programmatic intensity in Tanzania and Rwanda. We employed difference-in-difference analyses with fixed effects for countries and years as well as personal and time-varying area characteristics.

Main Outcome Measure  Adult all-cause mortality.

Results  We analyzed information on 1 538 612 adults, including 60 303 deaths, from 41 surveys in 27 countries, 9 of them focus countries. In 2003, age-adjusted adult mortality was 8.3 per 1000 adults in the focus countries (95% CI, 8.0-8.6) and 8.5 per 1000 adults (95% CI, 8.3-8.7) in the nonfocus countries. In 2008, mortality was 4.1 per 1000 (95% CI, 3.6-4.6) in the focus countries and 6.9 per 1000 (95% CI, 6.3-7.5) in the nonfocus countries. The adjusted odds ratio of mortality among adults living in focus countries compared with nonfocus countries between 2004 and 2008 was 0.84 (95% CI, 0.72-0.99; P = .03). Within Tanzania and Rwanda, the adjusted odds ratio of mortality for adults living in districts where PEPFAR operated more intensively was 0.83 (95% CI, 0.72-0.97; P = .02) and 0.75 (95% CI, 0.56-0.99; P = .04), respectively, compared with districts where it operated less intensively.

Conclusions  Between 2004 and 2008, all-cause adult mortality declined more in PEPFAR focus countries relative to nonfocus countries. It was not possible to determine whether PEPFAR was associated with mortality effects separate from reductions in HIV-specific deaths.

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Journal of the American Medical Association
Authors
Eran Bendavid
Grant Miller
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Objective To examine the relationship between hospital volume and in-hospital adverse events. Data Sources Patient safety indicator (PSI) was used to identify hospital-acquired adverse events in the Nationwide Inpatient Sample database in abdominal aortic aneurysm, coronary artery bypass graft, and Roux-en-Y gastric bypass from 2005 to 2008. Study Design In this observational study, volume thresholds were defined by mean year-specific terciles. PSI risk-adjusted rates were analyzed by volume tercile for each procedure. Principal Findings Overall, hospital volume was inversely related to preventable adverse events. High-volume hospitals had significantly lower risk-adjusted PSI rates compared to lower volume hospitals (p <.05). Conclusion These data support the relationship between hospital volume and quality health care delivery in select surgical cases. This study highlights differences between hospital volume and risk-adjusted PSI rates for three common surgical procedures and highlights areas of focus for future studies to identify pathways to reduce hospital-acquired events. © Health Research and Educational Trust.

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Health Services Research
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Abstract

BACKGROUND:

Patient safety is a national priority. Patient Safety Indicators (PSIs) monitor potential adverse events during hospital stays. Surgical specialty PSI benchmarks do not exist, and are needed to account for differences in the range of procedures performed, reasons for the procedure, and differences in patient characteristics. A comprehensive profile of adverse events in vascular surgery was created.

STUDY DESIGN:

The Nationwide Inpatient Sample was queried for 8 vascular procedures using ICD-9-CM codes from 2005 to 2009. Factors associated with PSI development were evaluated in univariate and multivariate analyses.

RESULTS:

A total of 1,412,703 patients underwent a vascular procedure and a PSI developed in 5.2%. PSIs were more frequent in female, nonwhite patients with public payers (p < 0.01). Patients at mid and low-volume hospitals had greater odds of developing a PSI (odds ratio [OR] = 1.17; 95% CI, 1.10-1.23 and OR = 1.69; 95% CI, 1.53-1.87). Amputations had highest PSI risk-adjusted rate and carotid endarterectomy and endovascular abdominal aortic aneurysm repair had lower risk-adjusted rate (p < 0.0001). PSI risk-adjusted rate increased linearly by severity of patient indication: claudicants (OR = 0.40; 95% CI, 0.35-0.46), rest pain patients (OR = 0.78; 95% CI, 0.69-0.90), ulcer (OR = 1.20; 95% CI, 1.07-1.34), and gangrene patients (OR = 1.85; 95% CI, 1.66-2.06).

CONCLUSIONS:

Patient safety events in vascular surgery were high and varied by procedure, with amputations and open abdominal aortic aneurysm repair having considerably more potential adverse events. PSIs were associated with black race, public payer, and procedure indication. It is important to note the overall higher rates of PSIs occurring in vascular patients and to adjust benchmarks for this surgical specialty appropriately.

Copyright © 2012 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

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J Am Coll Surg
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Objective: To assess the health literacy and numeracy skills of Spanish-speaking parents of young children and to validate a new Spanish language health literacy assessment for parents, the Spanish Parental Health Literacy Activities Test (PHLAT Spanish). Methods: Cross-sectional study of Spanish-speaking caregivers of young children (<30 months) enrolled at primary care clinics in 4 academic medical centers. Caregivers were administered the 10-item PHLAT in addition to validated tests of health literacy (S-TOFHLA) and numeracy (WRAT-3 Arithmetic). Psychometric analysis was used to examine item characteristics of the PHLAT-10 Spanish, to assess its correlation with sociodemographics and performance on literacy/numeracy assessments, and to generate a shorter 8-item scale (PHLAT-8). Results: Of 176 caregivers, 77% had adequate health literacy (S-TOFHLA), whereas only 0.6% had 9th grade or greater numeracy skills. Mean PHLAT-10 score was 41.6% (SD 21.1). Fewer than one-half (45.5%) were able to read a liquid antibiotic prescription label and demonstrate how much medication to administer within an oral syringe. Less than one-third (31.8%) were able to interpret a food label to determine whether it met WIC (Special supplemental nutrition program for Women, Infants, and Children) guidelines. Greater PHLAT-10 score was associated with greater years of education (r = 0.49), S-TOFHLA (r = 0.53), and WRAT-3 (r = 0.55) scores (P < .001). Internal reliability was good (Kuder-Richardson coefficient of reliability; KR-20 = 0.61). An 8-item scale was highly correlated with the full 10-item scale (r = 0.97, P < .001), with comparable internal reliability (KR-20 = 0.64). Conclusions: Many Spanish-speaking parents have difficulty performing health-related literacy and numeracy tasks. The Spanish PHLAT demonstrates good psychometric characteristics and may be useful for identifying parents who would benefit from receiving low-literacy child health information. Copyright © 2012 by Academic Pediatric Association.

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Academic Pediatrics
Authors
Lee M. Sanders
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Abstract

The structure of the contact network through which a disease spreads may influence the optimal use of resources for epidemic control. In this work, we explore how to minimize the spread of infection via quarantining with limited resources. In particular, we examine which links should be removed from the contact network, given a constraint on the number of removable links, such that the number of nodes which are no longer at risk for infection is maximized. We show how this problem can be posed as a non-convex quadratically constrained quadratic program (QCQP), and we use this formulation to derive a link removal algorithm. The performance of our QCQP-based algorithm is validated on small Erdo{double acute}s-Renyi and small-world random graphs, and then tested on larger, more realistic networks, including a real-world network of injection drug use. We show that our approach achieves near optimal performance and out-performs other intuitive link removal algorithms, such as removing links in order of edge centrality. © 2011 Elsevier Inc. All rights reserved.

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Mathematical Biosciences
Authors
Margaret L. Brandeau
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Background and Aims

Chronic hepatitis C (HCV) is a liver disease affecting over 3 million Americans. Liver biopsy is the gold standard for assessing liver fibrosis and is used as a benchmark for initiating treatment, though it is expensive and carries risks of complications. FibroTest is a non-invasive biomarker assay for fibrosis, proposed as a screening alternative to biopsy.

Methods

We assessed the cost-effectiveness of FibroTest and liver biopsy used alone or sequentially for six strategies followed by treatment of eligible U.S. patients: FibroTest only; FibroTest with liver biopsy for ambiguous results; FibroTest followed by biopsy to rule in; or to rule out significant fibrosis; biopsy only (recommended practice); and treatment without screening. We developed a Markov model of chronic HCV that tracks fibrosis progression. Outcomes were expressed as expected lifetime costs (2009 USD), quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICER).

Results

Treatment of chronic HCV without fibrosis screening is preferred for both men and women. For genotype 1 patients treated with pegylated interferon and ribavirin, the ICERs are $5,400/QALY (men) and $6,300/QALY (women) compared to FibroTest only; the ICERs increase to $27,200/QALY (men) and $30,000/QALY (women) with the addition of telaprevir. For genotypes 2 and 3, treatment is more effective and less costly than all alternatives. In clinical settings where testing is required prior to treatment, FibroTest only is more effective and less costly than liver biopsy. These results are robust to multi-way and probabilistic sensitivity analyses.

Conclusions

Early treatment of chronic HCV is superior to the other fibrosis screening strategies. In clinical settings where testing is required, FibroTest screening is a cost-effective alternative to liver biopsy.

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PLoS One
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Jeremy Goldhaber-Fiebert

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Faculty Lead, Center for Human and Planetary Health
Professor of Medicine (Infectious Diseases)
Professor of Epidemiology & Population Health (by courtesy)
Senior Fellow at the Freeman Spogli Institute for International Studies
Senior Fellow at the Woods Institute for the Environment
Faculty Affiliate at the Stanford Center on China's Economy and Institutions
steve_luby_2023-2_vert.jpg MD

Prof. Stephen Luby studied philosophy and earned a Bachelor of Arts summa cum laude from Creighton University. He then earned his medical degree from the University of Texas Southwestern Medical School at Dallas and completed his residency in internal medicine at the University of Rochester-Strong Memorial Hospital. He studied epidemiology and preventive medicine at the Centers for Disease Control and Prevention.

Prof. Luby's former positions include leading the Epidemiology Unit of the Community Health Sciences Department at the Aga Khan University in Karachi, Pakistan, for five years and working as a Medical Epidemiologist in the Foodborne and Diarrheal Diseases Branch of the U.S. Centers for Disease Control and Prevention (CDC) exploring causes and prevention of diarrheal disease in settings where diarrhea is a leading cause of childhood death.  Immediately prior to joining the Stanford faculty, Prof. Luby served for eight years at the International Centre for Diarrhoeal Diseases Research, Bangladesh (icddr,b), where he directed the Centre for Communicable Diseases. He was also the Country Director for CDC in Bangladesh.

During his over 25 years of public health work in low-income countries, Prof. Luby frequently encountered political and governance difficulties undermining efforts to improve public health. His work within the Center on Democracy, Development, and the Rule of Law (CDDRL) connects him with a community of scholars who provide ideas and approaches to understand and address these critical barriers.

 

Director of Research, Stanford Center for Innovation in Global Health
Affiliated faculty at the Center on Democracy, Development and the Rule of Law
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Those who live and die behind prison walls don’t usually get much public attention. Incarceration is, after all, meant to remove criminals from society. But contagious and potentially deadly diseases can’t be locked and left in a penitentiary, especially when infected inmates are eventually released.

The problem of prisoners and ex-convicts transmitting diseases to the general population is especially bad in the countries of the former Soviet Union, where rates of tuberculosis and drug-resistant strains of TB are among the world’s highest.

But Stanford researchers have identified solutions that could help curb tuberculosis in Russia, Latvia, Tajikistan and the 12 other countries in the region. Led by Jeremy Goldhaber-Fiebert, an assistant professor of medicine, the team has shown that a genetic TB and drug resistance screening tool called GeneXpert is more cost effective and better at reducing the spread of the disease than other methods currently recommended by the World Health Organization. Their findings were published online Nov. 27 in PLoS Medicine.

“Tuberculosis doesn’t stop at any border or any locked gate,” said Goldhaber-Fiebert, who is also a faculty member at Stanford Health Policy, a research center at the university’s Freeman Spogli Institute for International Studies.

“Drug-resistant TB is rampant in prisons,” he said. “When infected prisoners get out, they are thought to drive the TB epidemic in the general population. We are looking to find better ways to deal with that.”

About 400,000 cases of TB were diagnosed last year in the 15 former Soviet Union states – 40 times the number reported in the United States. Nearly 80,000 of the sick had drug-resistant TB. According to several studies, the prevalence of TB among the region’s prisoners is 10 times greater than that of the general population.

The WHO suggests three ways to screen for TB in prisons: relying on inmates to report symptoms, actively interviewing prisoners about their health, and administering chest X-rays. The organization doesn’t recommend one method over another, and currently, prisoners in the former Soviet Union are screened annually with miniature chest X-rays.

While X-rays can show whether a lung looks healthy, they don’t always catch TB. And when they do, they cannot differentiate between a TB that can be cured with standard medications and its drug-resistant cousins that require more expensive and extensive treatments.

That’s where GeneXpert has an upper hand.

Since it was introduced in 2005, the diagnostic has been hailed as a potentially powerful tool that can help to cut TB and drug-resistance rates by more accurately diagnosing people and getting them treated. With just a small sample of mucous analyzed by a machine, the GeneXpert system can instantly detect TB and its drug-resistant genetic mutations, well suited to mass screening within the prison systems of the former Soviet Union.

But the GeneXpert test is more expensive than alternative screening methods. And while it promises to be more effective, its impact on total costs had not been quantified in the former Soviet Union region until Goldhaber-Fiebert and his colleagues began their work nearly three years ago.

By developing computer models of the former Soviet Union’s prison populations, the team predicted that using GeneXpert can cut the prevalence of TB among inmates by about 20 percent within four years – provided the screening is combined with standard regimens of drug treatment for infected patients and for those with drug-resistant TB.

“For this to make sense, you need to have the right drugs to cure those individuals you identify,” Goldhaber-Fiebert said.

The additional cost of screening with GeneXpert averages to $71 per prisoner compared to the next best alternative approach, he said.

When compared to the decreases in illness and increases in survival, and factoring the financial and societal costs of TB in the broader population, the method makes good economic sense, he said.

“There is a large, direct value to using this technology for screening in prison settings, and there are potentially substantial secondary benefits to the general population of the former Soviet Union and to the world,” Goldhaber-Fiebert said.

Douglas K. Owens, a professor of medicine who is one of the paper’s co-authors and director of Stanford Health Policy, said the findings could give governments and medical experts the evidence they need to change the way they tackle TB.

“This is the kind of work we hope will inform policymaking about TB control,” Owens said. “We’ve shown there’s a more effective approach for trying to catch TB in prisons, and that means a better chance for preventing the disease from spreading.”

Co-authors on the PLoS Medicine paper also include former Stanford medical student Daniel Winetsky and current Stanford doctoral student in Management Science and Engineering, Diana Negoescu.

The researchers collaborated with the AIDS Foundation East-West. Funding for the study came from Äids Fonds, the International Research & Exchanges Board, the Department of Veterans Affairs, the National Institutes of Health, and Stanford.

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Russian prisoners with tuberculosis take their medicine. The problem of prisoners and ex-convicts transmitting diseases is especially bad in the countries of the former Soviet Union, where TB rates are among the world’s highest.
Reuters
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