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Active Surveillance Versus Watchful Waiting for Localized Prostate Cancer: A Model to Inform Decisions

Loeb, Stacy; Zhou, Qinlian; Siebert, Uwe; Rochau, Ursula; Jahn, Beate; Mühlberger, Nikolai; Carter, H Ballentine; Lepor, Herbert; Braithwaite, R Scott
BACKGROUND:An increasing proportion of prostate cancer is being managed conservatively. However, there are no randomized trials or consensus regarding the optimal follow-up strategy. OBJECTIVE:To compare life expectancy and quality of life between watchful waiting (WW) versus different strategies of active surveillance (AS). DESIGN, SETTING, AND PARTICIPANTS/METHODS:A Markov model was created for US men starting at age 50, diagnosed with localized prostate cancer who chose conservative management by WW or AS using different testing protocols (prostate-specific antigen every 3-6 mo, biopsy every 1-5 yr, or magnetic resonance imaging based). Transition probabilities and utilities were obtained from the literature. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS/UNASSIGNED:Primary outcomes were life years and quality-adjusted life years (QALYs). Secondary outcomes include radical treatment, metastasis, and prostate cancer death. RESULTS AND LIMITATIONS/CONCLUSIONS:All AS strategies yielded more life years compared with WW. Lifetime risks of prostate cancer death and metastasis were, respectively, 5.42% and 6.40% with AS versus 8.72% and 10.30% with WW. AS yielded more QALYs than WW except in cohorts age >65 yr at diagnosis, or when treatment-related complications were long term. The preferred follow-up strategy was also sensitive to whether people value short-term over long-term benefits (time preference). Depending on the AS protocol, 30-41% underwent radical treatment within 10 yr. Extending the surveillance biopsy interval from 1 to 5 yr reduced life years slightly, with a 0.26 difference in QALYs. CONCLUSIONS:AS extends life more than WW, particularly for men with higher-risk features, but this is partly offset by the decrement in quality of life since many men eventually receive treatment. PATIENT SUMMARY/UNASSIGNED:More intensive active surveillance protocols extend life more than watchful waiting, but this is partly offset by decrements in quality of life from subsequent treatment.
PMCID:5694372
PMID: 28844371
ISSN: 1873-7560
CID: 3070402

Potential return on investment of a family-centered early childhood intervention: a cost-effectiveness analysis

Hajizadeh, Negin; Stevens, Elizabeth R; Applegate, Melanie; Huang, Keng-Yen; Kamboukos, Dimitra; Braithwaite, R Scott; Brotman, Laurie M
BACKGROUND: ParentCorps is a family-centered enhancement to pre-kindergarten programming in elementary schools and early education centers. When implemented in high-poverty, urban elementary schools serving primarily Black and Latino children, it has been found to yield benefits in childhood across domains of academic achievement, behavior problems, and obesity. However, its long-term cost-effectiveness is unknown. METHODS: We determined the cost-effectiveness of ParentCorps in high-poverty, urban schools using a Markov Model projecting the long-term impact of ParentCorps compared to standard pre-kindergarten programming. We measured costs and quality adjusted life years (QALYs) resulting from the development of three disease states (i.e., drug abuse, obesity, and diabetes); from the health sequelae of these disease states; from graduation from high school; from interaction with the judiciary system; and opportunity costs of unemployment with a lifetime time horizon. The model was built, and analyses were performed in 2015-2016. RESULTS: ParentCorps was estimated to save $4387 per individual and increase each individual's quality adjusted life expectancy by 0.27 QALYs. These benefits were primarily due to the impact of ParentCorps on childhood obesity and the subsequent predicted prevention of diabetes, and ParentCorps' impact on childhood behavior problems and the subsequent predicted prevention of interaction with the judiciary system and unemployment. Results were robust on sensitivity analyses, with ParentCorps remaining cost saving and health generating under nearly all assumptions, except when schools had very small pre-kindergarten programs. CONCLUSIONS: Effective family-centered interventions early in life such as ParentCorps that impact academic, behavioral and health outcomes among children attending high-poverty, urban schools have the potential to result in longer-term health benefits and substantial cost savings.
PMCID:5635549
PMID: 29017527
ISSN: 1471-2458
CID: 2731682

Observational Study of the Effect of Patient Outreach on Return to Care: The Earlier the Better

Rebeiro, Peter F; Bakoyannis, Giorgos; Musick, Beverly S; Braithwaite, Ronald S; Wools-Kaloustian, Kara K; Nyandiko, Winstone; Some, Fatma; Braitstein, Paula; Yiannoutsos, Constantin T
BACKGROUND: The burden of HIV remains heaviest in resource-limited settings, where problems of losses to care, silent transfers, gaps in care, and incomplete mortality ascertainment have been recognized. METHODS: Patients in care at Academic Model Providing Access to Healthcare (AMPATH) clinics from 2001-2011 were included in this retrospective observational study. Patients missing an appointment were traced by trained staff; those found alive were counseled to return to care (RTC). Relative hazards of RTC were estimated among those having a true gap: missing a clinic appointment and confirmed as neither dead nor receiving care elsewhere. Sample-based multiple imputation accounted for missing vital status. RESULTS: Among 34,522 patients lost to clinic, 15,331 (44.4%) had a true gap per outreach, 2754 (8.0%) were deceased, and 837 (2.4%) had documented transfers. Of 15,600 (45.2%) remaining without active ascertainment, 8762 (56.2%) with later RTC were assumed to have a true gap. Adjusted cause-specific hazard ratios (aHRs) showed early outreach (a
PMCID:5597469
PMID: 28604501
ISSN: 1944-7884
CID: 2701762

Community-Based, Preclinical Patient Navigation for Colorectal Cancer Screening Among Older Black Men Recruited From Barbershops: The MISTER B Trial

Cole, Helen; Thompson, Hayley S; White, Marilyn; Browne, Ruth; Trinh-Shevrin, Chau; Braithwaite, Scott; Fiscella, Kevin; Boutin-Foster, Carla; Ravenell, Joseph
OBJECTIVES: To test the effectiveness of a preclinical, telephone-based patient navigation intervention to encourage colorectal cancer (CRC) screening among older Black men. METHODS: We conducted a 3-parallel-arm, randomized trial among 731 self-identified Black men recruited at barbershops between 2010 and 2013 in New York City. Participants had to be aged 50 years or older, not be up-to-date on CRC screening, have uncontrolled high blood pressure, and have a working telephone. We randomized participants to 1 of 3 groups: (1) patient navigation by a community health worker for CRC screening (PN), (2) motivational interviewing for blood pressure control by a trained counselor (MINT), or (3) both interventions (PLUS). We assessed CRC screening completion at 6-month follow-up. RESULTS: Intent-to-treat analysis revealed that participants in the navigation interventions were significantly more likely than those in the MINT-only group to be screened for CRC during the 6-month study period (17.5% of participants in PN, 17.8% in PLUS, 8.4% in MINT; P < .01). CONCLUSIONS: Telephone-based preclinical patient navigation has the potential to be effective for older Black men. Our results indicate the importance of community-based health interventions for improving health among minority men. (Am J Public Health. Published online ahead of print July 20, 2017: e1-e8. doi:10.2105/AJPH.2017.303885).
PMCID:5551599
PMID: 28727540
ISSN: 1541-0048
CID: 2640252

Risk-stratified versus Non-Risk-stratified Diagnostic Testing for Management of Suspected Acute Biliary Obstruction: Comparative Effectiveness, Costs, and the Role of MR Cholangiopancreatography

Kang, Stella K; Hoffman, David; Ferket, Bart; Kim, Michelle I; Braithwaite, R Scott
Purpose To analyze the cost effectiveness of the American Society for Gastrointestinal Endoscopy (ASGE) risk stratification guidelines versus magnetic resonance (MR) cholangiopancreatography-based treatment of patients with possible choledocholithiasis. Materials and Methods A decision-analytic model was constructed to compare cost and effectiveness of three diagnostic strategies for gallstone disease with possible choledocholithiasis: noncontrast MR cholangiopancreatography, contrast material-enhanced MR imaging/MR cholangiopancreatography, and ASGE risk stratification guidelines for diagnostic evaluation recommending endoscopy (high risk), MR cholangiopancreatography (intermediate risk), or no test (low risk). Analysis was performed from a U.S. health system perspective over 1-year and lifetime horizons. The model accounted for benign and malignant causes of biliary obstruction and procedural complications. Cost information was based on Medicare reimbursements. Sensitivity analysis assessed the impact of parameter variability on model results. Results Noncontrast MR cholangiopancreatography was most cost-effective in 45-55-year-old patients (less than $100 000 per quality-adjusted life-year [QALY] gained), while contrast-enhanced MR imaging was favored in younger adults. Risk-stratified testing was less costly than MR cholangiopancreatography, with long-term savings of $1870 and $2068 versus noncontrast and contrast-enhanced MR cholangiopancreatography, respectively, but was also less effective (-0.1814, -0.1831 QALY, respectively). The lifetime incremental cost per QALY for noncontrast MR cholangiopancreatography was $10 311. Contrast-enhanced MR imaging was favored with pretest probabilities of biliary stricture or malignancy 0%-73% for patients aged 20-44 years. For patients older than 55 years, ASGE guidelines maximized QALYs at the lowest cost. Conclusion Although adults older than 55 years of age are optimally evaluated by using ASGE guidelines, younger patients suspected of having acute biliary obstruction likely benefit from MR cholangiopancreatography rather than risk-stratified diagnostic imaging because of improved detection of choledocholithiasis and alternative causes of biliary obstruction. (c) RSNA, 2017 Online supplemental material is available for this article.
PMID: 28301778
ISSN: 1527-1315
CID: 2490102

Qualitative study on decision-making by prostate cancer physicians during active surveillance

Loeb, Stacy; Curnyn, Caitlin; Fagerlin, Angela; Braithwaite, Ronald Scott; Schwartz, Mark D; Lepor, Herbert; Carter, Herbert Ballentine; Sedlander, Erica
OBJECTIVE: To explore and identify factors that influence physicians' decisions while monitoring patients with prostate cancer on active surveillance (AS). SUBJECTS AND METHODS: A purposive sampling strategy was used to identify physicians treating prostate cancer from diverse clinical backgrounds and geographic areas across the USA. We conducted 24 in-depth interviews from July to December 2015, until thematic saturation was reached. The Applied Thematic Analysis framework was used to guide data collection and analysis. Interview transcripts were reviewed and coded independently by two researchers. Matrix analysis and NVivo software were used for organization and further analysis. RESULTS: Eight key themes emerged to explain variation in AS monitoring: (i) physician comfort with AS; (ii) protocol selection; (iii) beliefs about the utility and quality of testing; (iv) years of experience and exposure to AS during training; (v) concerns about inflicting 'harm'; (vi) patient characteristics; (vii) patient preferences; and (viii) financial incentives. CONCLUSION: These qualitative data reveal which factors influence physicians who manage patients on AS. There is tension between providing standardized care while also considering individual patients' needs and health status. Additional education on AS is needed during urology training and continuing medical education. Future research is needed to empirically understand whether any specific protocol is superior to tailored, individualized care.
PMCID:5555310
PMID: 27611479
ISSN: 1464-410x
CID: 2593252

What are the Patterns Between Depression, Smoking, Unhealthy Alcohol Use, and Other Substance Use Among Individuals Receiving Medical Care? A Longitudinal Study of 5479 Participants

Ruggles, Kelly V; Fang, Yixin; Tate, Janet; Mentor, Sherry M; Bryant, Kendall J; Fiellin, David A; Justice, Amy C; Braithwaite, R Scott
To evaluate and characterize the structure of temporal patterns of depression, smoking, unhealthy alcohol use, and other substance use among individuals receiving medical care, and to inform discussion about whether integrated screening and treatment strategies for these conditions are warranted. Using the Veterans Aging Cohort Study (VACS) we measured depression, smoking, unhealthy alcohol use and other substance use (stimulants, marijuana, heroin, opioids) and evaluated which conditions tended to co-occur within individuals, and how this co-occurrence was temporally structured (i.e. concurrently, sequentially, or discordantly). Current depression was associated with current use of every substance examined with the exception of unhealthy alcohol use. Current unhealthy alcohol use and marijuana use were also consistently associated. Current status was strongly predicted by prior status (p < 0.0001; OR = 2.99-22.34) however, there were few other sequential relationships. Associations in the HIV infected and uninfected subgroups were largely the same with the following exceptions. Smoking preceded unhealthy alcohol use and current smoking was associated with current depression in the HIV infected subgroup only (p < 0.001; OR = 1.33-1.41 and p < 0.001; OR = 1.25-1.43). Opioid use and current unhealthy alcohol use were negatively associated only in the HIV negative subgroup (p = 0.01; OR = 0.75). Patterns of depression, smoking, unhealthy alcohol use, and other substance use were temporally concordant, particularly with regard to depression and substance use. These patterns may inform future development of more integrated screening and treatment strategies.
PMCID:5542002
PMID: 27475945
ISSN: 1573-3254
CID: 2199312

Life-years lost to preventable causes-of-death in the us, 2014 [Meeting Abstract]

Taksler, G B; Rothberg, M B; Braithwaite, R S
BACKGROUND: Modifiable behavioral risk factors pose a substantial mortality burden in the US. We sought to explain the number of life-years lost to modifiable risk factors in 2014. METHODS: Based on data from the National Vital Statistics System, we developed a microsimulation model to assess the number of life-years lost to preventable disease risk factors. First, we simulated 2014 life expectancy in the US population aged >15 y, based on 28 competing risk factors (17 modifiable, such as hypertension, and 11 non-modifiable, such as genetics) that contributed to 19 mortality-causing conditions (which were based on the 10 leading causes-of-death for each age decile). An individual could have multiple risk factors (e.g., hypertension, obesity) and multiple mortality-causing conditions (e.g., breast cancer, heart disease) but could only die of a single cause. All individuals faced background mortality risk based on age, sex and race. To estimate the number of life-years lost to each modifiable risk factor, we examined the change in mortality for a series of counterfactual US populations that each eliminated a single risk factor. We compared the results with the change in life-years lost for an "optimal" population that eliminated all modifiable risk factors. Recognizing that some less common factors might place substantial burden on small population subgroups, we also estimated life expectancy gained in individuals with each modifiable risk factor. RESULTS: In 2014, the greatest number of preventable life-years were lost to obesity (303 million life-years, 22.2% of total preventable life-years), diabetes (267 million life-years, 19.6% of total), hypertension (209 million life-years, 15.4% of total), tobacco (206 million life-years, 15.1% of total) and hyperlipidemia (+130 million life-years, 9.5% of total). Fewer life-years were lost to alcohol misuse, HPV, sexual behaviors, bipolar disease, anxiety, vaccines, hepatitis B/C, illicit drug use, head trauma and environmental toxins (each 1-3%of total). However, in affected individuals, a substantial number of years were lost to alcohol misuse (+17.5 years/individual), tobacco (+10.0 years/ individual), hepatitis B/C (+7.6 years/individual) and bipolar disease (+7.3 years/individual). Individual losses to obesity (+4.8 years/individual), diabetes (+2.6 years/individual), hyperlipidemia (+1.0 years/individual) and hypertension (+0.9 years/individual) were smaller. CONCLUSIONS: We analyzed the contribution of modifiable behavioral risk factors to causes-of-death in the US population. Our findings suggest that obesity resulted in 47% more life-years lost than tobacco in 2014, but tobacco caused similar life-years lost as hypertension. Results also highlight tension between population health approaches to mortality prevention (which were influenced by both gains in life expectancy and number of affected individuals in each age group) vs. individualized goals for use in clinical practice (which were only influenced by gains in life expectancy)
EMBASE:615580896
ISSN: 0884-8734
CID: 2554262

Effects of naloxone distribution alone or in combination with addiction treatment with or without pre-exposure prophylaxis for HIV prevention in people who inject drugs: a cost-effectiveness modelling study

Uyei, Jennifer; Fiellin, David A; Buchelli, Marianne; Rodriguez-Santana, Ramon; Braithwaite, R Scott
BACKGROUND:In the USA, an epidemic of opioid overdose deaths is occurring, many of which are from heroin. Combining naloxone distribution with linkage to addiction treatment or pre-exposure prophylaxis (PrEP) for HIV prevention through syringe service programmes has the potential to save lives and be cost-effective. We estimated the outcomes and cost-effectiveness of five alternative strategies: no additional intervention, naloxone distribution, naloxone distribution plus linkage to addiction treatment, naloxone distribution plus PrEP, and naloxone distribution plus linkage to addiction treatment and PrEP. METHODS:We developed a decision analytical Markov model to simulate opioid overdose, HIV incidence, overdose-related deaths, and HIV-related deaths in people who inject drugs in Connecticut, USA. Model input parameters were derived from published sources. We compared each strategy with no intervention, as well as simultaneously considering all strategies. Sensitivity analysis was done for all variables. Linkage to addiction treatment was referral to an opioid treatment programme for methadone. Endpoints were survival, life expectancy, quality-adjusted life-years (QALYs), number and percentage of overdose deaths averted, number of HIV-related deaths averted, total costs (in 2015 US$) associated with each strategy, and incremental cost per QALY gained. FINDINGS/RESULTS:In the base-case analysis, compared with no additional intervention, the naloxone distribution strategy yielded an incremental cost-effectiveness ratio (ICER) of $323 per QALY, and naloxone distribution plus linkage to addiction treatment was cost saving compared with no additional intervention (greater effectiveness and less expensive). The most efficient strategies (ie, those conferring the greatest health benefit for a particular budget) were naloxone distribution combined with linkage to addiction treatment (cost saving), and naloxone distribution combined with PrEP and linkage to addiction treatment (ICER $95 337 per QALY) at a willingness-to-pay threshold of $100 000. In probabilistic sensitivity analysis, the combination of naloxone distribution, PrEP, and linkage to addiction treatment was the optimal strategy in 37% of iterations and the combination of naloxone distribution and linkage to addiction treatment was the optimal strategy in 34% of iterations. INTERPRETATION/CONCLUSIONS:Naloxone distribution through syringe service programmes is cost-effective compared with syringe distribution alone, but when combined with linkage to addiction treatment is cost saving compared with no additional services. A strategy that combines naloxone distribution, PrEP, and linkage to addiction treatment results in greater health benefits in people who inject drugs and is also cost-effective. FUNDING/BACKGROUND:State of Connecticut Department of Public Health and the National Institute of Mental Health.
PMID: 29253386
ISSN: 2468-2667
CID: 2892592

Betting on the fastest horse: Using computer simulation to design a combination HIV intervention for future projects in Maharashtra, India

Ruggles, Kelly V; Patel, Anik R; Schensul, Stephen; Schensul, Jean; Nucifora, Kimberly; Zhou, Qinlian; Bryant, Kendall; Braithwaite, R Scott
OBJECTIVE: To inform the design of a combination intervention strategy targeting HIV-infected unhealthy alcohol users in Maharashtra, India, that could be tested in future randomized control trials. METHODS: Using probabilistic compartmental simulation modeling we compared intervention strategies targeting HIV-infected unhealthy alcohol users on antiretroviral therapy (ART) in Maharashtra, India. We tested interventions targeting four behaviors (unhealthy alcohol consumption, risky sexual behavior, depression and antiretroviral adherence), in three formats (individual, group based, community) and two durations (shorter versus longer). A total of 5,386 possible intervention combinations were tested across the population for a 20-year time horizon and intervention bundles were narrowed down based on incremental cost-effectiveness analysis using a two-step probabilistic uncertainty analysis approach. RESULTS: Taking into account uncertainty in transmission variables and intervention cost and effectiveness values, we were able to reduce the number of possible intervention combinations to be used in a randomized control trial from over 5,000 to less than 5. The most robust intervention bundle identified was a combination of three interventions: long individual alcohol counseling; weekly Short Message Service (SMS) adherence counseling; and brief sex risk group counseling. CONCLUSIONS: In addition to guiding policy design, simulation modeling of HIV transmission can be used as a preparatory step to trial design, offering a method for intervention pre-selection at a reduced cost.
PMCID:5584966
PMID: 28873452
ISSN: 1932-6203
CID: 2687672