[Show abstract][Hide abstract] ABSTRACT: Aging is associated with a decline in multiple aspects of cognitive function, with spatial cognition being particularly sensitive to age-related decline. Environmental stressors, such as high-fat diet (HFD) exposure, that produce a diabetic phenotype and metabolic dysfunction may indirectly lead to exacerbated brain aging and promote the development of cognitive deficits. The present work investigated whether exposure to HFD exacerbates age-related cognitive deficits in adult versus aged mice. Adult (5 months old) and aged (15 months old) mice were exposed to control diet or HFD for three months prior to, and throughout, behavioral testing. Anxiety-like behavior in the light-dark box test, discrimination learning and memory in the novel object/place recognition tests, and spatial learning and memory in the Barnes maze test were assessed. HFD resulted in significant gains in body weight and fat mass content with adult mice gaining significantly more weight and adipose tissue due to HFD than aged mice. Weight gain was attributed to food calories sourced from fat, but not total calorie intake. HFD increased fasting insulin levels in all mice, but adult mice showed a greater increase relative to aged mice. Behaviorally, HFD increased anxiety-like behavior in adult but not aged mice without significantly affecting spatial cognition. In contrast, aged mice fed either control or HFD diet displayed deficits in novel place discrimination and spatial learning. Our results suggest that adult mice are more susceptible to the physiological and anxiety-like effects of HFD consumption than aged mice, while aged mice displayed deficits in spatial cognition regardless of dietary influence. We conclude that although HFD induces systemic metabolic dysfunction in both adult and aged mice, overall cognitive function was not adversely affected under the current experimental conditions.
PLoS ONE 10/2015; 10(10):e0140034. DOI:10.1371/journal.pone.0140034 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
Studies suggest that cervical cancer screening practice in the United States is inefficient. The cost and health implications of nonadherence in the screening process compared with recommended guidelines are uncertain.
To estimate the benefits, costs, and cost-effectiveness of current cervical cancer screening practice and assess the value of screening improvements.
Model-based cost-effectiveness analysis.
New Mexico HPV Pap Registry; medical literature.
Cohort of women eligible for routine screening.
Current cervical cancer screening practice; improved adherence to guidelines-based screening interval, triage testing, diagnostic referrals, and precancer treatment referrals.
Reductions in lifetime cervical cancer risk, quality-adjusted life-years (QALYs), lifetime costs, incremental cost-effectiveness ratios, and incremental net monetary benefits (INMBs).
Results of base-case analysis:
Current screening practice was associated with lower health benefit and was not cost-effective relative to guidelines-based strategies. Improvements in the screening process were associated with higher QALYs and small changes in costs. Perfect adherence to screening every 3 years with cytologic testing and adherence to colposcopy/biopsy referrals were associated with the highest INMBs ($759 and $741, respectively, at a willingness-to-pay threshold of $100 000 per QALY gained); together, the INMB increased to $1645.
Results of sensitivity analysis:
Current screening practice was inefficient in 100% of simulations. The rank ordering of screening improvements according to INMBs was stable over a range of screening inputs and willingness-to-pay thresholds.
The effect of human papillomavirus vaccination was not considered.
The added health benefit of improving adherence to guidelines, especially the 3-year interval for cytologic screening and diagnostic follow-up, may justify additional investments in interventions to improve U.S. cervical cancer screening practice.
Primary funding source:
U.S. National Cancer Institute.
Annals of internal medicine 09/2015; 163(8). DOI:10.7326/M15-0420 · 17.81 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
One billion children live in war-affected regions of the world. We conducted the first cost-effectiveness analysis of an intervention for war-affected youth in sub-Saharan Africa, as well as a broader cost analysis.
The Youth Readiness Intervention (YRI) is a behavioural treatment for reducing functional impairment associated with psychological distress among war-affected young persons. A randomized controlled trial was conducted in Freetown, Sierra Leone, from July 2012 to July 2013. Participants (n = 436, aged 15-24) were randomized to YRI (n = 222) or care as usual (n = 214). Functional impairment was indexed by the World Health Organization Disability Assessment Scale; scores were converted to quality-adjusted life years (QALYs). An 'ingredients approach' estimated financial and economic costs, assuming a societal perspective. Incremental cost-effectiveness ratios (ICERs) were also expressed in terms of gains across dimensions of mental health and schooling. Secondary analyses explored whether intervention effects were largest among those worst-off (upper quartile) at baseline.
Retention at 6-month follow-up was 85% (n = 371). The estimated economic cost of the intervention was $104 per participant. Functional impairment was lower among YRI recipients, compared with controls, following the intervention but not at 6-month follow-up, and yielded an ICER of $7260 per QALY gained. At 8-month follow-up, teachers' interviews indicated that YRI recipients observed higher school enrolment [P < 0.001, odds ratio (OR) 8.9], denoting a cost of $431 per additional school year gained, as well as better school attendance (P = 0.007, OR 34.9) and performance (P = 0.03, effect size = -1.31). Secondary analyses indicated that the intervention was cost-effective among those worst-off at baseline, yielding an ICER of $3564 per QALY gained.
The YRI is not cost-effective at a willingness-to-pay threshold of three times average gross domestic product per capita. However, results indicate that the YRI translated into a range of benefits, such as improved school enrolment, not captured by cost-effectiveness analysis. We also outline areas for modification to improve cost-effectiveness in future trials.
clinicaltrials.gov Identifier: RPCGA-YRI-21003.
Health Policy and Planning 09/2015; DOI:10.1093/heapol/czv078 · 3.47 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: World Health Organization guidelines recommend that cervical cancer screening programs should prioritize screening coverage in women aged 30 to 49 years. Decisions about target ages and screening frequency depend upon local burden of disease, costs, and capacity. We used cost and test performance data from the START-UP demonstration projects in India, Nicaragua, and Uganda to evaluate the cost-effectiveness of screening at various start ages, intervals, and frequencies. We calibrated a mathematical simulation model of cervical carcinogenesis to each country and compared screening with careHPV (cervical and vaginal sampling), visual inspection with acetic acid (VIA), and cytology between the ages of 25 and 50 years, at frequencies of once to three times in a lifetime, at 5- and 10-year intervals. Screening with careHPV (cervical sampling) was the most effective and cost-effective strategy in all settings; careHPV (vaginal sampling) was only slightly less effective. The most critical ages for screening are between ages 30 and 45 years. Within this age range, screening at certain ages may be relatively more cost-effective, but cancer risk reductions are similar for a given screening test and interval. Screening three times between 30 and 45 years was very cost-effective and reduced cancer risk by ~50%.
[Show abstract][Hide abstract] ABSTRACT: Cervical cancer is the leading cause of cancer death among women in El Salvador. Utilizing data from the Cervical Cancer Prevention in El Salvador (CAPE) demonstration project, we assessed the health and economic impact of HPV-based screening and two different algorithms for the management of women who test HPV-positive, relative to existing Pap-based screening. We calibrated a mathematical model of cervical cancer to epidemiologic data from El Salvador and compared three screening algorithms for women aged 30 to 65 years: 1) HPV screening every 5 years followed by referral to colposcopy for HPV-positive women (Colposcopy Management [CM]); 2) HPV screening every 5 years followed by treatment with cryotherapy for eligible HPV-positive women (Screen and Treat [ST]); and 3) Pap screening every 2 years followed by referral to colposcopy for Pap-positive women (Pap). Potential harms and complications associated with overtreatment were not assessed. Under base case assumptions of 65% screening coverage, HPV-based screening was more effective than Pap, reducing cancer risk by approximately 60% (Pap: 50%). ST was the least costly strategy, and cost $2,040 per year of life saved. ST remained the most attractive strategy as visit compliance, costs, coverage, and test performance were varied. We conclude that a screen-and-treat algorithm within an HPV-based screening program is very cost-effective in El Salvador, with a cost-effectiveness ratio below per capita GDP. This article is protected by copyright. All rights reserved.
International Journal of Cancer 01/2015; 137(4). DOI:10.1002/ijc.29438 · 5.09 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Purpose: Standardized screening protocols for anal cancer do not yet exist despite the growing evidence that this human papillomavirus (HPV)-related cancer is preceded by premalignant stages, which if detected and removed, may prevent progression to cancer. Men who have sex with men (MSM) who are human immunodeficiency virus (HIV)-infected are among those at highest risk for anal cancer development. In order to inform policy recommendations in the United States, we estimated the health benefits and resource trade-offs associated with alternative primary anal cancer screening strategies for HIV-infected MSM.
Method: We developed and calibrated a natural history microsimulation model that reflects the most recent understanding of anal carcinogenesis, accounting for interactions between HPV type-specific infections, CD4 lymphocyte strata, and anti-retroviral treatment (ART) status. Relevant strategies involved cytology-based screening, which varied by screening interval (i.e., every 1-3 years) and age at which men initiate screening (i.e., 30 vs. 40 years). Triage of abnormal results involved high-resolution anoscopy. Primary outcomes included discounted life expectancy (3% per year), cancer risk reduction and resource use (number of anoscopies performed). We calculated the incremental harm-benefit ratio (IHBR) in terms of the additional number of anoscopies required per year of life saved (YLS) for each strategy compared with the next most harmful strategy. Sensitivity analyses were conducted on test characteristics, and parameter uncertainty for progression to invasive cancer.
Results: Compared with no screening, the least intensive strategy is projected to reduce cancer risk by 24%, while the most intensive strategy may reduce cancer risk by 66% among HIV-infected MSM. All strategies that initiated screening at age 40 were dominated by strategies that started at age 30. For those strategies on the harm-benefit frontier, triennial cytology-based screening required an additional 7.2 anoscopies per YLS compared with no screening, while the most intensive screening strategy (annual) required an additional 40.3 anoscopies per YLS, compared with biennial screening. The rank-order of strategies was preserved when we assumed a less sensitive anal cytology test.
Conclusion: For HIV-infected MSM, the most efficient anal cancer screening strategies involve starting at age 30; however, the optimal screening interval is unclear, as more intensive strategies require explicit trade-offs between the harms and benefits, and depend on capacity constraints and society's willingness-to-pay for life-years and other health benefits.
The 36th Annual Meeting of the Society for Medical Decision Making; 10/2014
[Show abstract][Hide abstract] ABSTRACT: Background: Current prophylactic vaccines against human papillomavirus (HPV) target two of the most oncogenic types, HPV-16 and -18, which contribute to roughly 70% of cervical cancers worldwide. Second-generation HPV vaccines include a 9-valent vaccine, which targets five additional oncogenic HPV types (i.e., 31, 33, 45, 52, and 58) that contribute to another 15-30% of cervical cancer cases. The objective of this study was to determine a range of vaccine costs for which the 9-valent vaccine would be cost-effective in comparison to the current vaccines in two less developed countries (i.e., Kenya and Uganda).
PLoS ONE 09/2014; 9(9):e106836. DOI:10.1371/journal.pone.0106836 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Mathematical models of cervical cancer have been widely used to evaluate the comparative effectiveness and cost-effectiveness of preventive strategies. Major advances in the understanding of cervical carcinogenesis motivate the creation of a new disease paradigm in such models. To keep pace with the most recent evidence, we updated a previously developed microsimulation model of human papillomavirus (HPV) infection and cervical cancer to reflect 1) a shift towards health states based on HPV rather than poorly reproducible histological diagnoses and 2) HPV clearance and progression to precancer as a function of infection duration and genotype, as derived from the control arm of the Costa Rica Vaccine Trial (2004-2010). The model was calibrated leveraging empirical data from the New Mexico Surveillance, Epidemiology, and End Results Registry (1980-1999) and a state-of-the-art cervical cancer screening registry in New Mexico (2007-2009). The calibrated model had good correspondence with data on genotype- and age-specific HPV prevalence, genotype frequency in precancer and cancer, and age-specific cancer incidence. We present this model in response to a call for new natural history models of cervical cancer intended for decision analysis and economic evaluation at a time when global cervical cancer prevention policy continues to evolve and evidence of the long-term health effects of cervical interventions remains critical.
American Journal of Epidemiology 07/2014; 180(5). DOI:10.1093/aje/kwu159 · 5.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
Human papillomavirus (HPV) vaccines are ideally administered before HPV exposure; therefore, catch-up programs for girls past adolescence have not been readily funded. We evaluated the benefits and cost-effectiveness of a delayed, 1-year female catch-up vaccination program in Norway.
We calibrated a dynamic HPV transmission model to Norwegian data and projected the costs and benefits associated with 8 HPV-related conditions while varying the upper vaccination age limit to 20, 22, 24, or 26 years. We explored the impact of vaccine protection in women with prior vaccine-targeted HPV infections, vaccine cost, coverage, and natural- and vaccine-induced immunity.
The incremental benefits and cost-effectiveness decreased as the upper age limit for catch-up increased. Assuming a vaccine cost of $150/dose, vaccination up to age 20 years remained below Norway's willingness-to-pay threshold (approximately $83 000/quality-adjusted life year gained); extension to age 22 years was cost-effective at a lower cost per dose ($50-$75). At high levels of vaccine protection in women with prior HPV exposure, vaccinating up to age 26 years was cost-effective. Results were stable with lower coverage.
HPV vaccination catch-up programs, 5 years after routine implementation, may be warranted; however, even at low vaccine cost per dose, the cost-effectiveness of vaccinating beyond age 22 years remains uncertain.
The Journal of Infectious Diseases 07/2014; 211(2). DOI:10.1093/infdis/jiu413 · 6.00 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Increasingly, countries have introduced female vaccination against human papillomavirus (HPV), causally linked to several cancers and genital warts, but few have recommended vaccination of boys. Declining vaccine prices and strong evidence of vaccine impact on reducing HPV-related conditions in both women and men prompt countries to reevaluate whether HPV vaccination of boys is warranted.
A previously-published dynamic model of HPV transmission was empirically calibrated to Norway. Reductions in the incidence of HPV, including both direct and indirect benefits, were applied to a natural history model of cervical cancer, and to incidence-based models for other non-cervical HPV-related diseases. We calculated the health outcomes and costs of the different HPV-related conditions under a gender-neutral vaccination program compared to a female-only program.
Vaccine price had a decisive impact on results. For example, assuming 71% coverage, high vaccine efficacy and a reasonable vaccine tender price of $75 per dose, we found vaccinating both girls and boys fell below a commonly cited cost-effectiveness threshold in Norway ($83,000/quality-adjusted life year (QALY) gained) when including vaccine benefit for all HPV-related diseases. However, at the current market price, including boys would not be considered 'good value for money.' For settings with a lower cost-effectiveness threshold ($30,000/QALY), it would not be considered cost-effective to expand the current program to include boys, unless the vaccine price was less than $36/dose. Increasing vaccination coverage to 90% among girls was more effective and less costly than the benefits achieved by vaccinating both genders with 71% coverage.
At the anticipated tender price, expanding the HPV vaccination program to boys may be cost-effective and may warrant a change in the current female-only vaccination policy in Norway. However, increasing coverage in girls is uniformly more effective and cost-effective than expanding vaccination coverage to boys and should be considered a priority.
PLoS ONE 03/2014; 9(3):e89974. DOI:10.1371/journal.pone.0089974 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We studied the cost-effectiveness of cervical cancer prevention strategies in the Central and Eastern Europe and Central Asia (CEECA) region. The cost-effectiveness of human papillomavirus (HPV)16/18 vaccination of 12 year-old girls was calculated for 28 countries, under the assumption that vaccination prevents 70% of all cervical cancer cases and that cervical cancer and all-cause mortality rates are stable without vaccination. At three-dose vaccination costs of I$ 100 per vaccinated girl (currency 2005 international dollars), HPV16/18 vaccination was very cost-effective in 25 out of 28 countries using the country's gross domestic product (GDP) per capita as cost-effectiveness threshold (criterion by World Health Organization). A three-dose vaccination cost of I$ 100 is within the current range of vaccine costs in European immunization programs, and therefore our results indicate that HPV vaccination may be good value for money. To evaluate the cost-effectiveness of cervical cancer screening combined with vaccination, we calibrated a published simulation model to HPV genotype data collected in Slovenia, Poland, and Georgia. The screening interval was varied at 3, 6, and 10 years starting at age 25 or 30 and ending at age 60. In Slovenia and Poland, combined vaccination and 10-yearly HPV (DNA) screening (vaccination coverage 70%, screening coverage per round 70%) was very cost-effective when the cost of three-dose vaccination was I$ 100 per vaccinated girl. More intensive screening was very cost-effective when the screening coverage per round was 30% or 50%. In Georgia, 10-yearly Pap screening was very cost-effective in unvaccinated women. Vaccination combined with 10-yearly HPV screening was likely to be cost-effective if the three-dose vaccination cost was I$ 50 per vaccinated girl. To conclude, cervical cancer prevention strategies utilizing both HPV16/18 vaccination and HPV screening are very cost-effective in countries with sufficient resources. In low-resource settings, low vaccine pricing is essential for strategies of combined vaccination and screening to be cost-effective. This article forms part of a regional report entitled "Comprehensive Control of HPV Infections and Related Diseases in the Central and Eastern Europe and Central Asia Region" Vaccine Volume 31, Supplement 7, 2013. Updates of the progress in the field are presented in a separate monograph entitled "Comprehensive Control of HPV Infections and Related Diseases" Vaccine Volume 30, Supplement 5, 2012.
[Show abstract][Hide abstract] ABSTRACT: To date, no studies have evaluated the cost-effectiveness of human papillomavirus (HPV) vaccination in countries in the Extended Middle East and North Africa (EMENA) region. We synthesized population and epidemiologic data for 20 EMENA countries using a model-based approach to estimate averted cervical cancer cases and deaths, disability-adjusted life years (DALYs) and cost-effectiveness ratios (I$ [international dollars] per DALY averted) associated with HPV vaccination of pre-adolescent girls. We utilized additional epidemiologic data from Algeria, Lebanon, and Turkey to evaluate select cervical cancer screening strategies either alone or in combination with vaccination. Results showed that pre-adolescent vaccination of five consecutive birth cohorts at 70% coverage has the potential to prevent over 180,000 cervical cancer cases. Cases averted varied by country, largely due to differences in cancer burden and population size; 69% of cases averted occurred in the three GAVI-eligible countries in EMENA. Despite the low cervical cancer incidence in EMENA, we found that HPV vaccination was cost-effective using a threshold of each country's gross domestic product per capita (a common metric for evaluating cost-effectiveness) in all but five countries at a cost per vaccinated girl of I$25 ($5 per dose). However, cost-effectiveness diminished with increasing vaccine cost; at a cost of I$200 per vaccinated girl, HPV vaccination was cost-effective in only five countries. When the cost per vaccinated girl exceeded I$50 in Lebanon and Turkey and I$150 in Algeria, screening alone was most attractive. We identified opportunities to improve upon current national screening guidelines, involving less frequent screening every 3-5 years. While pre-adolescent HPV vaccination promises to be a cost-effective strategy in most EMENA countries at low costs, decision makers will need to consider many other factors, such as affordability, acceptability, feasibility, and competing health priorities, when making decisions about cervical cancer prevention. This article forms part of a regional report entitled "Comprehensive Control of HPV Infections and Related Diseases in the Extended Middle East and North Africa Region" Vaccine Volume 31, Supplement 6, 2013. Updates of the progress in the field are presented in a separate monograph entitled "Comprehensive Control of HPV Infections and Related Diseases" Vaccine Volume 30, Supplement 5, 2012.