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ivar.jpg MD, MPH

Ivar S. Kristiansen is a professor of public health at the Department of Health Management and Health Economics, University of Oslo, Norway and adjunct professor of pharmacoeconomics at the University of Southern Denmark at Odense. He is visiting scholar at Stanford Health Policy 2011-12.

Kristiansen’s research focuses on technology assessment, cost-effectiveness analysis, and valuation of health outcomes. Also, he has worked for many years on the topic of risk communication in the context of chronic diseases when time is a crucial factor. He is one of the founders of Odense Risk Group.

Kristiansen received an MD from the University of Oslo in 1972, completed his internship at the University Hospital of Trondheim and then worked for 10 years as a combined family physician/public health officer in two remote communities in Norway. He received an MPH degree from Harvard University i 1986 and a PhD from University of Tromsø, Norway in 1996. Kristiansen is a past-President of the Norwegian Public Health Association and has served on numerous public committees in Norway.

Adjunct Affiliate at the Center for Health Policy and the Department of Health Policy
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As incomes rise around the world, health experts expect a more troubling figure to increase as well: the number of diabetics in developing countries.

In China and India – two of the world’s most populous nations with fast-paced economies – the prevalence of diabetes is expected to double by 2025. Between 15 and 20 percent of their adult population will develop the disease as household budgets increase, diets change to include more calories and new health problems emerge.

But China, India and other developing countries are not fully prepared to deal with the rising trend of diabetes. And a growing number of diabetics aren’t getting the care they need to prevent serious complications, Stanford researchers say.

Even with insurance, many diabetics don’t have essential medications that could help them manage their conditions. In many cases, people are spending a great deal of their household incomes to pay for their treatment, said Jeremy Goldhaber-Fiebert, an assistant professor of medicine who led the research team.

“Public and private health insurance programs aren’t providing sufficient protection for diabetics in many developing countries,” said Goldhaber-Fiebert, a faculty member at Stanford Health Policy at the university’s Freeman Spogli Institute for International Studies. “People with insurance aren’t doing markedly better than those who don’t have it. Health insurance and health systems need to be re-oriented to better address chronic diseases like diabetes.”

Findings from the study are online and will be published in the Jan. 24 edition of Diabetes Care, the journal of the American Diabetes Association. The journal article was co-authored by Jay Bhattacharya, an associate professor of medicine and Stanford Health Policy faculty member; and Crystal Smith-Spangler, an instructor at Stanford’s Department of Medicine and an investigator at the Palo Alto VA Health Care System.

Failure to adequately manage diabetes will lead to more severe health problems like blindness, heart disease and kidney failure. It also harms the otherwise healthy, Goldhaber-Fiebert said.

Diabetes often strikes people at an age when they’re taking care of children and elderly parents. To sideline these primary caretakers as dependants will lead to a heavy burden for communities and create an obstacle for economic growth, he added.

Using responses to a global survey conducted by the World Health Organization in 2002 and 2003, Goldhaber-Fiebert and his colleagues examined data from 35 low- and middle-income countries in Asia, Latin America, Africa and Eastern Europe to determine whether diabetics with insurance were more likely to have medication than those without insurance.

They also wanted to know whether insured diabetics have a lower risk of “catastrophic medical spending,” a term the researchers define as spending more than 25 percent of a household income on medical care.

“Surprisingly, diabetics with insurance were no more likely to have the medications they need than uninsured diabetics,” Goldhaber-Fiebert said. “They were also no less likely to suffer catastrophic medical spending.”

There are many reasons why health insurance may not protect diabetics in developing countries against high out-of-pocket spending. In some cases, there’s a lack of sufficient medication – such as insulin – that regulate glucose levels. Without those drugs, there’s a greater risk of complications that often lead to more hospitalizations and more expenses.

In other cases, co-payments and deductibles are too high. Sometimes, drugs and medical services to prevent diabetes complications are not covered. And doctors and hospitals don’t always accept insurance.

“Better policies are needed to provide sufficient protection and care for diabetics in the developing world,” Goldhaber-Fiebert said.

Without medications to manage diabetes and prevent secondary complications, the condition will worsen and the burden of catastrophic spending will increase, he said.

“It’s important to get ahead of the curve and prepare so there’s an infrastructure in place to deal with these health and cost issues,” he said.

While preventing diabetes in the first place would be ideal, programs and policies must be established to care for the many cases that will surely continue to exist.

“There isn’t a single country that’s managed to entirely arrest or reverse the trend of diabetes,” he said. “Programs that focus on primary prevention are extremely important, but the reality is that the developing world faces hundreds of millions of diabetes cases that are unlikely to all be prevented.”

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Abstract

BACKGROUND:

Injection drug use (IDU) and heterosexual virus transmission both contribute to the growing mixed HIV epidemics in Eastern Europe and Central Asia. In Ukraine-chosen in this study as a representative country-IDU-related risk behaviors cause half of new infections, but few injection drug users (IDUs) receive methadone substitution therapy. Only 10% of eligible individuals receive antiretroviral therapy (ART). The appropriate resource allocation between these programs has not been studied. We estimated the effectiveness and cost-effectiveness of strategies for expanding methadone substitution therapy programs and ART in mixed HIV epidemics, using Ukraine as a case study.

METHODS AND FINDINGS:

We developed a dynamic compartmental model of the HIV epidemic in a population of non-IDUs, IDUs using opiates, and IDUs on methadone substitution therapy, stratified by HIV status, and populated it with data from the Ukraine. We considered interventions expanding methadone substitution therapy, increasing access to ART, or both. We measured health care costs, quality-adjusted life years (QALYs), HIV prevalence, infections averted, and incremental cost-effectiveness. Without incremental interventions, HIV prevalence reached 67.2% (IDUs) and 0.88% (non-IDUs) after 20 years. Offering methadone substitution therapy to 25% of IDUs reduced prevalence most effectively (to 53.1% IDUs, 0.80% non-IDUs), and was most cost-effective, averting 4,700 infections and adding 76,000 QALYs compared with no intervention at US$530/QALY gained. Expanding both ART (80% coverage of those eligible for ART according to WHO criteria) and methadone substitution therapy (25% coverage) was the next most cost-effective strategy, adding 105,000 QALYs at US$1,120/QALY gained versus the methadone substitution therapy-only strategy and averting 8,300 infections versus no intervention. Expanding only ART (80% coverage) added 38,000 QALYs at US$2,240/QALY gained versus the methadone substitution therapy-only strategy, and averted 4,080 infections versus no intervention. Offering ART to 80% of non-IDUs eligible for treatment by WHO criteria, but only 10% of IDUs, averted only 1,800 infections versus no intervention and was not cost effective.

CONCLUSIONS:

Methadone substitution therapy is a highly cost-effective option for the growing mixed HIV epidemic in Ukraine. A strategy that expands both methadone substitution therapy and ART to high levels is the most effective intervention, and is very cost effective by WHO criteria. When expanding ART, access to methadone substitution therapy provides additional benefit in infections averted. Our findings are potentially relevant to other settings with mixed HIV epidemics. Please see later in the article for the Editors' Summary.

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PLoS Medicine
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Douglas K. Owens
Margaret L. Brandeau
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Abstract HIV-2 group A is predominant in different parts of the world, especially Africa, Portugal, Spain, France, the United Kingdom, the United States, Korea, and India. Among the Asian countries, India accounts for about 95% of all HIV-2 infections. The prevalence of HIV-2 has been reported from various states of India such as Maharashtra, Goa, Tamil Nadu, West Bengal, and Uttar Pradesh. In the present study, we analyzed transmembrane region (gp36) sequences of 10 HIV-2 group A Indian strains, isolated from Indian HIV-2-seropositive individuals. HIV Blast analysis for the 1.0-Kb region of the gp36 transmembrane region has shown that all these sequences belong to HIV-2 group A. Phylogenetic analysis indicated that the sequences cluster with HIV-2 group A sequences of Cameroon and Senegal. The epitope found at position 645-656 (YELQKLNSWDVF), previously reported as a broadly neutralizing determinant, was very well conserved in all 10 study sequences. The percentage similarity between Indian and South African HIV-2 group A gp36 sequences was 90% (range 86-100, SD 2.8) and with other nonsubtype A clades was 84% (range 77-100, SD 6.06) indicating overall less variability among the reported HIV-2 sequences. Similarly, the consensus amino acid sequences of the envelope transmembrane region of HIV-1 (gp41) and HIV-2 (gp36) is quite synonymous, indicating 87% similarity; however, limited information is available about the gp36 transmembrane region of the prevalent HIV 2 group A Indian strain. The rate of synonymous substitutions reported in the gp105 region was significantly higher, suggesting lower virulence of HIV-2, which does translate into a lower rate of evolution, while the dN/dS ratio for the gp36 transmembrane region was less than one, indicating its conservation and significance (p<0.05) in structural and functional constraints.

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AIDS Research and Human Retroviruses
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Background. The effect of antiretroviral therapy (ART) interruption or intensification on health-related quality of life (HRQoL) in advanced HIV patients is unknown.

Objective. To assess the impact of temporary treatment interruption and intensification of ART on HRQoL.

Design. A 2 x 2 factorial open label randomized controlled trial.

Setting. Hospitals in the United States, Canada, and the United Kingdom.

Patients. Multidrug resistant (MDR) HIV patients.

Intervention. Patients were randomized to receive a 12-wk interruption or not, and ART intensification or standard ART.

Measurements. The Health Utilities Index (HUI3), EQ-5D, standard gamble (SG), time tradeoff (TTO), visual analog scale (VAS), and the Medical Outcomes Study HIV Health Survey (MOS-HIV).

Results. There were no significant differences in HRQoL among the four groups during follow-up; however, there was a temporary significant decline in HRQoL on some measures within the interruption group during interruption (HUI3 −0.05, P = 0.03; VAS −5.9, P = 0.002; physical health summary −2.9, P = 0.001; mental health summary −1.9, P = 0.02). Scores declined slightly overall during follow-up. Multivariate analysis showed significantly lower HRQoL associated with some clinical events.

Limitations. The results may not apply to HIV patients who have not experienced multiple treatment failures or who have not developed MDR HIV.

Conclusions. Temporary ART interruption and ART intensification provided neither superior nor inferior HRQoL compared with no interruption and standard ART. Among surviving patients, HRQoL scores declined only slightly over years of follow-up in this advanced HIV cohort; however, approximately one-third of patients died during the trial follow up. Lower HRQoL was associated with adverse clinical events.

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Medical Decision Making
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Mark Holodniy
Douglas K. Owens
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Background Injection drug use (IDU) and heterosexual virus transmission both contribute to the growing mixed HIV epidemics in Eastern Europe and Central Asia. In Ukraine—chosen in this study as a representative country—IDU-related risk behaviors cause half of new infections, but few injection drug users (IDUs) receive methadone substitution therapy. Only 10% of eligible individuals receive antiretroviral therapy (ART). The appropriate resource allocation between these programs has not been studied. We estimated the effectiveness and cost-effectiveness of strategies for expanding methadone substitution therapy programs and ART in mixed HIV epidemics, using Ukraine as a case study.

Methods and Findings We developed a dynamic compartmental model of the HIV epidemic in a population of non-IDUs, IDUs using opiates, and IDUs on methadone substitution therapy, stratified by HIV status, and populated it with data from the Ukraine. We considered interventions expanding methadone substitution therapy, increasing access to ART, or both. We measured health care costs, quality-adjusted life years (QALYs), HIV prevalence, infections averted, and incremental cost-effectiveness. Without incremental interventions, HIV prevalence reached 67.2% (IDUs) and 0.88% (non-IDUs) after 20 years. Offering methadone substitution therapy to 25% of IDUs reduced prevalence most effectively (to 53.1% IDUs, 0.80% non-IDUs), and was most cost-effective, averting 4,700 infections and adding 76,000 QALYs compared with no intervention at US$530/QALY gained. Expanding both ART (80% coverage of those eligible for ART according to WHO criteria) and methadone substitution therapy (25% coverage) was the next most cost-effective strategy, adding 105,000 QALYs at US$1,120/QALY gained versus the methadone substitution therapy-only strategy and averting 8,300 infections versus no intervention. Expanding only ART (80% coverage) added 38,000 QALYs at US$2,240/QALY gained versus the methadone substitution therapy-only strategy, and averted 4,080 infections versus no intervention. Offering ART to 80% of non-IDUs eligible for treatment by WHO criteria, but only 10% of IDUs, averted only 1,800 infections versus no intervention and was not cost effective.

Conclusions Methadone substitution therapy is a highly cost-effective option for the growing mixed HIV epidemic in Ukraine. A strategy that expands both methadone substitution therapy and ART to high levels is the most effective intervention, and is very cost effective by WHO criteria. When expanding ART, access to methadone substitution therapy provides additional benefit in infections averted. Our findings are potentially relevant to other settings with mixed HIV epidemics.

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PLoS Med
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Douglas K. Owens
Margaret L. Brandeau
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BACKGROUND: Evidence suggests that gut flora may play an important role in the pathophysiology of the irritable bowel syndrome (IBS). We evaluated rifaximin, a minimally absorbed antibiotic, as treatment for IBS.

METHODS: In two identically designed, phase 3, double-blind, placebo-controlled trials (TARGET 1 and TARGET 2), patients who had IBS without constipation were randomly assigned to either rifaximin at a dose of 550 mg or placebo, three times daily for 2 weeks, and were followed for an additional 10 weeks. The primary end point, the proportion of patients who had adequate relief of global IBS symptoms, and the key secondary end point, the proportion of patients who had adequate relief of IBS-related bloating, were assessed weekly. Adequate relief was defined as self-reported relief of symptoms for at least 2 of the first 4 weeks after treatment. Other secondary end points included the percentage of patients who had a response to treatment as assessed by daily self-ratings of global IBS symptoms and individual symptoms of bloating, abdominal pain, and stool consistency during the 4 weeks after treatment and during the entire 3 months of the study.

RESULTS: Significantly more patients in the rifaximin group than in the placebo group had adequate relief of global IBS symptoms during the first 4 weeks after treatment (40.8% vs. 31.2%, P=0.01, in TARGET 1; 40.6% vs. 32.2%, P=0.03, in TARGET 2; 40.7% vs. 31.7%, P<0.001, in the two studies combined). Similarly, more patients in the rifaximin group than in the placebo group had adequate relief of bloating (39.5% vs. 28.7%, P=0.005, in TARGET 1; 41.0% vs. 31.9%, P=0.02, in TARGET 2; 40.2% vs. 30.3%, P<0.001, in the two studies combined). In addition, significantly more patients in the rifaximin group had a response to treatment as assessed by daily ratings of IBS symptoms, bloating, abdominal pain, and stool consistency. The incidence of adverse events was similar in the two groups.

CONCLUSIONS: Among patients who had IBS without constipation, treatment with rifaximin for 2 weeks provided significant relief of IBS symptoms, bloating, abdominal pain, and loose or watery stools. (Funded by Salix Pharmaceuticals; ClinicalTrials.gov numbers, NCT00731679 and NCT00724126.).

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New England Journal of Medicine
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The Affordable Care Act promises to add 32 million Americans to the rolls of the insured at a time when there is a shortage of primary care providers. There is broad consensus that the next phase of reform must slow the growth of health care costs and improve value through payment reforms, including bundling of payments and payments for episodes of care. Some savings will derive from implementation of innovative models of care, such as accountable care organizations, medical homes, transitional care, and community-based care. We believe that if we are to bridge the gap in primary care and establish new approaches to care delivery, all health care providers must be permitted to practice to the fullest extent of their knowledge and competence. This will require establishing a standardized and broadened scope of practice for advanced-practice registered nurses — in particular, nurse practitioners — for all states.

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The New England Journal of Medicine
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John (Jack) W. Rowe
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