Search

Background: Methods for matching in longitudinal cohort studies, such as sequential stratification and time-varying propensity scores, facilitate causal inferences in the context of time-dependent treatments that are not randomized where patient eligibility or treatment status changes over time. The tradeoffs in available approaches have not been compared previously, so we compare two methods using simulations based on a retrospective cohort of patients eligible for weight loss surgery, some of whom received it., Methods: This study compares matching completeness, bias, coverage, and precision among three approaches to longitudinal matching: (1) time-varying propensity scores (tvPS), (2) sequential stratification that matches exactly on all covariates used in tvPS (SS-Full) and (3) sequential stratification that exact matches on a subset of covariates (SS-Selected). These comparisons are made in the context of a deep sampling frame (50:1) and a shallow sampling frame (5:1) of eligible comparators. A simulation study was employed to estimate the relative performance of these approaches., Results: In 1,000 simulations each, tvPS retained more than 99.9% of treated patients in both the deep and shallow sampling frames, while a smaller proportion of treated patients were retained for SS-Full (91.6%) and SS-Selected (98.2%) in the deep sampling frame. In the shallow sampling frame, sequential stratification retained many fewer treated patients (73.9% SS-Full, 92.0% SS-Selected) than tvPS yet coverage, precision and bias were comparable for tvPS, SS-Full and SS-Selected in the deep and shallow sampling frames., Conclusion: Time-varying propensity scores have comparable performance to sequential stratification in terms of coverage, bias, and precision, with superior match completeness. While performance was generally comparable across methods, greater match completeness makes tvPS an attractive option for longitudinal matching studies where external validity is highly valued., Competing Interests: Declarations Ethics approval and consent to participate This study was approved by the Kaiser Permanente Southern California Institutional Review Board (#12440) with waivers of informed consent and Privacy Rule authorization. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: The use of potentially inappropriate medications (PIMs) is associated with increased risk of hospitalizations and emergency room visits and varies by racial and ethnic subgroups. Medicare's nationwide medication therapy management (MTM) program requires that Part D plans offer an annual comprehensive medication review (CMR) to all beneficiaries who qualify, and provides a platform to reduce PIM use. The objective of this study was to assess the impact of CMR on PIM discontinuation in Medicare beneficiaries and whether this differed by race or ethnicity., Methods: Retrospective cohort study of community-dwelling Medicare Part D beneficiaries ≥66 years of age who were eligible for MTM from 2013 to 2019 based on 5% Medicare fee-for-service claims data linked to the 100% MTM data file. Among those using a PIM, MTM-eligible CMR recipients were matched to non-recipients via sequential stratification. The probability of PIM discontinuation was estimated using regression models that pooled yearly subcohorts accounting for within-beneficiary correlations. The most common PIMs that were discontinued after CMR were reported., Results: We matched 24,368 CMR recipients to 24,368 CMR non-recipients during the observation period. Median age was 74-75, 35% were males, most were White beneficiaries (86%-87%), and the median number of PIMs was 1. In adjusted analyses, CMR receipt was positively associated with PIM discontinuation (adjusted relative risk [aRR]: 1.26, 95% CI: 1.20-1.32). There was no evidence of differential impact of CMR by race or ethnicity. The PIMs most commonly discontinued after CMR were glimepiride, zolpidem, digoxin, amitriptyline, and nitrofurantoin., Conclusions: Among Medicare beneficiaries who are using a PIM, CMR receipt was associated with PIM discontinuation, suggesting that greater CMR use could facilitate PIM reduction for all racial and ethnic groups., (© 2024 The American Geriatrics Society.)

Importance: Comprehensive medication reviews (CMRs) are offered to qualifying US Medicare beneficiaries annually to optimize medication regimens and therapeutic outcomes. In 2016, Medicare adopted CMR completion as a Star Rating quality measure to encourage the use of CMRs., Objective: To examine trends in CMR completion rates before and after 2016 and whether racial, ethnic, and socioeconomic disparities in CMR completion changed., Design, Setting, and Participants: This observational study using interrupted time-series analysis examined 2013 to 2020 annual cohorts of community-dwelling Medicare beneficiaries aged 66 years and older eligible for a CMR as determined by Part D plans and by objective minimum eligibility criteria. Data analysis was conducted from September 2022 to February 2024., Exposure: Adoption of CMR completion as a Star Rating quality measure in 2016., Main Outcome and Measures: CMR completion modeled via generalized estimating equations., Results: The study included a total of 561 950 eligible beneficiaries, with 253 561 in the 2013 to 2015 cohort (median [IQR] age, 75.8 [70.7-82.1] years; 90 778 male [35.8%]; 6795 Asian [2.7%]; 24 425 Black [9.6%]; 7674 Hispanic [3.0%]; 208 621 White [82.3%]) and 308 389 in the 2016 to 2020 cohort (median [IQR] age, 75.1 [70.4-80.9] years; 126 730 male [41.1%]; 8922 Asian [2.9%]; 27 915 Black [9.1%]; 7635 Hispanic [2.5%]; 252 781 White [82.0%]). The unadjusted CMR completion rate increased from 10.2% (7379 of 72 225 individuals) in 2013 to 15.6% (14 185 of 90 847 individuals) in 2015 and increased further to 35.8% (18 376 of 51 386 individuals) in 2020, in part because the population deemed by Part D plans to be MTM-eligible decreased by nearly half after 2015 (90 487 individuals in 2015 to 51 386 individuals in 2020). Among a simulated cohort based on Medicare minimum eligibility thresholds, the unadjusted CMR completion rate increased but to a lesser extent, from 4.4% in 2013 to 12.6% in 2020. Compared with White beneficiaries, Asian and Hispanic beneficiaries experienced greater increases in likelihood of CMR completion after 2016 but remained less likely to complete a CMR. Dual-Medicaid enrollees also experienced greater increases in likelihood of CMR completion as compared with those without either designation, but still remained less likely to complete CMR., Conclusion and Relevance: This study found that adoption of CMR completion as a Star Rating quality measure was associated with higher CMR completion rates. The increase in CMR completion rates was achieved partly because Part D plans used stricter eligibility criteria to define eligible patients. Reductions in disparities for eligible Asian, Hispanic, and dual-Medicaid enrollees were seen, but not eliminated. These findings suggest that quality measures can inform plan behavior and could be used to help address disparities.

Recent publicity around the use of new antiobesity medications (AOMs) has focused the attention of patients and healthcare providers on the role of pharmacotherapy in the treatment of obesity. Newer drug treatments have shown greater efficacy and safety compared with older drug treatments, yet access to these drug treatments is limited by providers' discomfort in prescribing, bias, and stigma around obesity, as well as by the lack of insurance coverage. Now more than ever, healthcare providers must be able to discuss the risks and benefits of the full range of antiobesity medications available to patients, and to incorporate both guideline based advice and emerging real world clinical evidence into daily clinical practice. The tremendous variability in response to antiobesity medications means that clinicians need to use a flexible approach that takes advantage of specific features of the antiobesity medication selected to provide the best option for individual patients. Future research is needed on how best to use available drug treatments in real world practice settings, the potential role of combination therapies, and the cost effectiveness of antiobesity medications. Several new drug treatments are being evaluated in ongoing clinical trials, suggesting that the future for pharmacotherapy of obesity is bright., Competing Interests: Competing interests: KHL reported receiving personal fees from National Committee for Quality Assurance for serving as a faculty member on a continuing medical education activity about obesity outside the submitted work. DA reported receiving reimbursement from the American Society for Metabolic and Bariatric Surgery for travel expenses to the 2023 annual meeting. DHB has received research funding and compensation for consulting work from Eli Lilly and Novo Nordisk. CES has no conflicts of interest to declare., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Purpose of Review: Pharmacoequity refers to the goal of ensuring that all patients have access to high-quality medications, regardless of their race, ethnicity, gender, or other characteristics. The goal of this article is to review current evidence on disparities in access to cardiovascular drug therapies across sociodemographic subgroups, with a focus on heart failure, atrial fibrillation, and dyslipidemia., Recent Findings: Considerable and consistent disparities to life-prolonging heart failure, atrial fibrillation, and dyslipidemia medications exist in clinical trial representation, access to specialist care, prescription of guideline-based therapy, drug affordability, and pharmacy accessibility across racial, ethnic, gender, and other sociodemographic subgroups. Researchers, health systems, and policy makers can take steps to improve pharmacoequity by diversifying clinical trial enrollment, increasing access to inpatient and outpatient cardiology care, nudging clinicians to increase prescription of guideline-directed medical therapy, and pursuing system-level reforms to improve drug access and affordability., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Importance: Medicare finances health care for most US patients with end-stage kidney disease (ESKD), regardless of age. The 2011 Medicare prospective payment system (PPS) for dialysis reduced reimbursement for hemodialysis, and the 2014 Patient Protection and Affordable Care Act (ACA) Marketplace increased patient access to new private insurance options, potentially influencing organizations that provide health care, such as hospitals, nursing homes, and dialysis facilities, to adjust their payer mix away from Medicare sources., Objective: To describe Medicare enrollment trends among patients with incident ESKD in 2006 to 2016., Design, Setting, and Participants: This retrospective cohort study involved US patients aged 18 to 64 years who were not enrolled in Medicare at dialysis initiation in 2006 to 2016, with 1-year follow-up through 2017. Data analysis was conducted April 2021 to June 2022., Exposures: The exposure of interest was a 3-category indicator of time, whether patients initiated dialysis before policies were enacted (2006-2010), in the first years of the Medicare ESKD PPS (2011-2013), or during the Medicare ESKD PPS and implementation of the ACA Marketplace (2014-2016)., Main Outcomes and Measures: Patient-level Medicare enrollment through the first year of dialysis. Logistic regression and Cox models were used to examine associations of time, patient characteristics, and Medicare enrollment, adjusting for patient demographic, clinical, and market-level characteristics., Results: Of 335 157 patients aged 18 to 64 years with ESKD not actively enrolled in Medicare when they initiated dialysis in 2006 to 2016, the mean (SD) age was 49.9 (10.8) years, 198 164 (59.1%) were men, 188 290 (56.2%) were White, and 313 622 (93.6%) received in-center hemodialysis. New Medicare enrollment was higher in 2006 to 2010 (110 582 patients [73.1%]) than after the Medicare ESKD PPS and ACA Marketplace in 2014 to 2016 (55 382 patients [58.5%]). In adjusted analyses, declining Medicare enrollment was associated with implementation of 2011 Medicare ESKD PPS and 2014 ACA policies and was disproportionately lower among younger, racially minoritized, and ethnically Hispanic patients., Conclusions and Relevance: There was declining Medicare enrollment among new dialysis patients associated with the 2011 Medicare ESKD PPS and 2014 ACA Marketplace that raise concerns about benefits and harms to patients and payers and continued disparities in kidney care. As the dialysis payer mix moves toward higher proportions of patients not covered by Medicare, it will be important to understand the implications for health care system and patient outcomes.

Objectives: Clinicians increasingly believe they should discuss costs with their patients. We aimed to learn what strategies clinicians, clinic leaders, and health systems can use to facilitate vital cost-of-care conversations., Methods: We conducted focus groups and semi-structured interviews with outpatient clinicians at two US academic medical centers. Clinicians recalled previous cost conversations and described strategies that they, their clinic, or their health system could use to facilitate cost conversations. Independent coders recorded, transcribed, and coded focus groups and interviews., Results: Twenty-six clinicians participated between December 2019 and July 2020: general internists (23%), neurologists (27%), oncologists (15%), and rheumatologists (35%). Clinicians proposed the following strategies: teach clinicians to initiate cost conversations; systematically collect financial distress information; partner with patients to identify costs; provide accurate insurance coverage and/or out-of-pocket cost information via the electronic health record; develop local lists of lowest-cost pharmacies, laboratories, and subspecialists; hire financial counselors; and reduce indirect costs (e.g., parking)., Conclusions: Despite considerable barriers to discussing, identifying, and reducing patient costs, clinicians described a variety of strategies for improving cost communication in the clinic., Practice Implications: Health systems and clinic leadership can and should implement these strategies to improve the financial health of the patients they serve., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Importance: The dialysis industry is highly concentrated, with large dialysis organizations now providing dialysis for more than 85% of patients with kidney failure in the United States. In 2011, Medicare introduced a new Prospective Payment System (PPS) for end-stage kidney disease, which bundled payment for dialysis care into 1 payment per patient. Trends in dialysis facility consolidation after the PPS went into effect are unknown., Objective: To determine whether the introduction of the PPS in 2011 was associated with an acceleration in acquisitions and closures of small dialysis chains (<20 facilities) and independently owned facilities., Design Setting and Participants: This retrospective cohort study included all Medicare-certified independent or small chain-affiliated dialysis facilities in the continental US between 2006 and 2016. Data were obtained from Medicare and the US Renal Data System and were analyzed in 2020., Exposures: The PPS., Main Outcomes and Measures: Discrete time hazard models were used to estimate the odds of acquisition and closure before the PPS (2006-2010) vs after the PPS (2011-2016). Analyses controlled for facility, market, and regional demographic characteristics. The average predicted marginal probabilities of acquisition and closure over time were estimated., Results: The proportion of small chain-affiliated and independently owned facilities declined from 29% (1383 of 4750 facilities) in 2006 to 15% (1038 of 6738) in 2016. Among 13 481 facility-years, 6352 (47%) were for profit, and mean (SD) census was 68 (59) patients. Overall, 3286 (24%) facilities opened during the observation period. The proportion of acquisitions that occurred each year varied from 1.1% (12 of 1065 facilities in 2015) to 7.2% (86 of 1192 facilities in 2012), while closures varied from 0.8% (9 of 1065 facilities in 2015) to 2.2% (28 of 1286 facilities in 2010), making both fairly rare. There was a 3.48 higher odds of acquisition in the post-PPS period compared with the pre-PPS period (95% CI, 1.62-7.47; P  = .001). The odds of closure before and after the PPS were not statistically significantly different (odds ratio, 2.03; 95% CI, 0.61-6.73; P  = .25). Facilities that opened during the observation period had a 7.2% higher predicted probability of acquisition compared with older facilities (95% CI, 5.4%-9.0%; P  < .001)., Conclusions and Relevance: In this cohort study of continental US Medicare-certified dialysis facilities, small-chain and independently owned facilities retained a declining share of the dialysis market. Further research should evaluate the effect of continued dialysis market consolidation on patient access, health care utilization, and clinical outcomes., Competing Interests: Conflict of Interest Disclosures: Dr Sloan reports grants from the National Institutes of Health (NIH) outside the submitted work. Dr Maciejewski reports grants from NIH and the Department of Veterans Affairs, a contract from the National Committee for Quality Assurance, and ownership of Amgen stock owing to his spouse’s employment outside the submitted work. Dr Coffman reports grants from NIH and the Department of Veterans Affairs during the conduct of the study. Dr Wang reports grants from the National Institute of Diabetes and Digestive and Kidney Diseases, the Department of Veterans Affairs, and the Agency for Healthcare Research and Quality; a contract with the National Committee for Quality Assurance; and honoraria from NIH outside the submitted work. No other disclosures were reported., (Copyright 2021 Sloan CE et al. JAMA Health Forum.)

Importance: One-third of US residents have trouble paying their medical bills. They often turn to their physicians for help navigating health costs and insurance coverage., Objective: To determine whether physicians can accurately estimate out-of-pocket expenses when they are given all of the necessary information about a drug's price and a patient's insurance plan., Design, Setting, and Participants: This national mail-in survey used a random sample of US physicians. The survey was sent to 900 outpatient physicians (300 each of primary care, gastroenterology, and rheumatology). Physicians were excluded if they were in training, worked primarily for the Veterans Administration or Indian Health Service, were retired, or reported 0% outpatient clinical effort. Analyses were performed from July to December 2020., Main Outcomes and Measures: In a hypothetical vignette, a patient was prescribed a new drug costing $1000/month without insurance. A summary of her private insurance information was provided, including the plan's deductible, coinsurance rates, copays, and out-of-pocket maximum. Physicians were asked to estimate the drug's out-of-pocket cost at 4 time points between January and December, using the plan's 4 types of cost-sharing: (1) deductibles, (2) coinsurance, (3) copays, and (4) out-of-pocket maximums. Multivariate linear regression was used to assess differences in performance by specialty, adjusting for attitudes toward cost conversations, demographics, and clinical characteristics., Results: The response rate was 45% (405 of 900) and 371 respondents met inclusion criteria. Among the respondents included in this study, 59% (n = 220) identified as male, 23% (n = 84) as Asian, 3% (n = 12) as Black, 6% (n = 24) as Hispanic, and 58% (n = 216) as White; 30% (n = 112) were primary care physicians, 35% (n = 128) were gastroenterologists, and 35% (n = 131) were rheumatologists; and the mean (SD) age was 49 (10) years. Overall, 52% of physicians (n = 192) accurately estimated costs before the deductible was met, 62% (n = 228) accurately used coinsurance information, 61% (n = 224) accurately used copay information, and 57% (n = 210) accurately estimated costs once the out-of-pocket maximum was met. Only 21% (n = 78) of physicians answered all 4 questions correctly. Ability to estimate out-of-pocket costs was not associated with specialty, attitudes toward cost conversations, or clinic characteristics., Conclusions and Relevance: This survey study found that many US physicians have difficulty estimating out-of-pocket costs, even when they have access to their patients' insurance plans. The mechanics involved in calculating real-time out-of-pocket costs are complex. These findings suggest that increased price transparency and simpler insurance cost-sharing mechanisms are needed to enable informed cost conversations at the point of prescribing.

Peritoneal dialysis (PD), a home-based treatment for kidney failure, is associated with similar mortality, higher quality of life, and lower costs compared with hemodialysis. Yet <10% of patients receive PD. Access to this alternative treatment, vis-à-vis providers' supply of PD services, may be an important factor but has been sparsely studied in the current era of national payment reform for dialysis care. We describe temporal and regional variation in PD supply among Medicare-certified dialysis facilities from 2006 to 2013. The average proportion of facilities offering PD per hospital referral region increased from 40% (2006) to 43% (2013). PD supply was highest in hospital referral regions with higher percentage of facilities in urban areas ( p = .004), prevalence of PD use ( p < .0001), percentage of White end-stage renal disease patients ( p = .02), and per capita income ( p = .02). Disparities in PD access persist in rural, non-White, and low-income regions. Policy efforts to further increase regional PD supply should focus on these underserved communities.

Background: Prior studies have shown peritoneal dialysis (PD) patients to have lower or equivalent mortality to patients who receive in-center hemodialysis (HD). Medicare's 2011 bundled dialysis prospective payment system encouraged expansion of home-based PD with unclear impacts on patient outcomes. This paper revisits the comparative risk of mortality between HD and PD among patients with incident end-stage kidney disease initiating dialysis in 2006-2013., Research Design: We conducted a retrospective cohort study comparing 2-year all-cause mortality among patients with incident end-stage kidney disease initiating dialysis via HD and PD in 2006-2013, using data from the US Renal Data System and Medicare. Analysis was conducted using Cox proportional hazards models fit with inverse probability of treatment weighting that adjusted for measured patient demographic and clinical characteristics and dialysis market characteristics., Results: Of the 449,652 patients starting dialysis between 2006 and 2013, the rate of PD use in the first 90 days increased from 9.3% of incident patients in 2006 to 14.2% in 2013. Crude 2-year mortality was 27.6% for patients dialyzing via HD and 16.7% for patients on PD. In adjusted models, there was no evidence of mortality differences between PD and HD before and after bundled payment (hazard ratio, 0.96; 95% confidence interval, 0.89-1.04; P=0.33)., Conclusions: Overall mortality for HD and PD use was similar and mortality differences between modalities did not change before versus after the 2011 Medicare dialysis bundled payment, suggesting that increased use of home-based PD did not adversely impact patient outcomes., Competing Interests: M.L.M. reports ownership of Amgen stock due to his spouse’s employment. The remaining authors declare no conflict of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Caring for patients with end-stage kidney disease (ESKD) in the United States is challenging, due in part to the complex epidemiology of the disease's progression as well as the ways in which care is delivered. As CKD progresses toward ESKD, the number of comorbidities increases and care involves multiple healthcare providers from multiple subspecialties. This occurs in the context of a fragmented US healthcare delivery system that is traditionally siloed by provider specialty, organization, as well as systems of payment and administration. This article describes the role of care fragmentation in the delivery of optimal ESKD care and identifies research gaps in the evidence across the continuum of care. We then consider the impact of care fragmentation on ESKD care from the patient and health system perspectives and explore opportunities for system-level interventions aimed at improving care for patients with ESKD., (© 2020 Wiley Periodicals LLC.)

Background and Objectives: Peritoneal dialysis (PD) for ESKD is associated with similar mortality, higher quality of life, and lower costs compared with hemodialysis (HD), but has historically been underused. We assessed the effect of the 2011 Medicare prospective payment system (PPS) for dialysis on PD initiation, modality switches, and stable PD use., Design, Setting, Participants, & Measurements: Using US Renal Data System and Medicare data, we identified all United States patients with ESKD initiating dialysis before (2006-2010) and after (2011-2013) PPS implementation, and observed their modality for up to 2 years after dialysis initiation. Using logistic regression models, we examined the associations between PPS and early PD experience (any PD 1-90 days after initiation), late PD use (any PD 91-730 days after initiation), and modality switches (PD-to-HD or HD-to-PD 91-730 days after initiation). We adjusted for patient, dialysis facility, and regional characteristics., Results: Overall, 619,126 patients with incident ESKD received dialysis at Medicare-certified facilities, 2006-2013. Observed early PD experience increased from 9.4% before PPS to 12.6% after PPS. Observed late PD use increased from 12.1% to 16.1%. In adjusted analyses, PPS was associated with increased early PD experience (odds ratio [OR], 1.51; 95% confidence interval [95% CI], 1.47 to 1.55; P <0.001) and late PD use (OR, 1.47; 95% CI, 1.45 to 1.50; P <0.001). In subgroup analyses, late PD use increased in part due to an increase in HD-to-PD switches among those without early PD experience (OR, 1.59; 95% CI, 1.52 to 1.66; P <0.001) and a decrease in PD-to-HD switches among those with early PD experience (OR, 0.92; 95% CI, 0.87 to 0.98; P =0.004)., Conclusions: More patients started, stayed on, and switched to PD after dialysis payment reform. This occurred without a substantial increase in transfers to HD., (Copyright © 2019 by the American Society of Nephrology.)

Background: Although cytogenetics-based prognostication systems are well described in acute myeloid leukemia (AML), overall survival (OS) remains highly variable within risk groups. An integrated genetic prognostic (IGP) model using cytogenetics plus mutations in nine genes was recently proposed for patients ≤60 years to improve classification. This model has not been validated in clinical practice., Methods and Findings: We retrospectively studied 197 patients with newly diagnosed de novo AML. We compared OS curves among the mutational profiles defined by the IGP model. The IGP model assigned patients with intermediate cytogenetics as having favorable, intermediate or unfavorable mutational profiles. The IGP model reassigned 50 of 137 patients with intermediate cytogenetics to favorable or unfavorable mutational profiles. Median OS was 2.8 years among 14 patients with intermediate cytogenetics and favorable mutational profiles (mutant NPM1 and mutant IDH1 or IDH2) and 1.3 years among patients with intermediate mutational profiles. Among patients with intermediate cytogenetics labeled as having unfavorable mutational profiles, median OS was 0.8 years among 24 patients with FLT3-ITD positive AML and high-risk genetic changes (trisomy 8, TET2 and/or DNMT3A) and 1.7 years among 12 patients with FLT3-ITD negative AML and high-risk mutations (TET2, ASXL1 and/or PHF6). OS for patients with intermediate cytogenetics and favorable mutational profiles was similar to OS for patients with favorable cytogenetics (p = 0.697) and different from patients with intermediate cytogenetics and intermediate mutational profiles (p = 0.028). OS among patients with FLT3-ITD positive AML and high-risk genetic changes was similar to patients with unfavorable cytogenetics (p = 0.793) and different from patients with intermediate IGP profile (p = 0.022). Patients with FLT3-ITD negative AML and high-risk mutations, defined as 'unfavorable' in the IGP model, had OS similar to patients with intermediate IGP profile (p = 0.919)., Conclusions: The IGP model was not completely validated in our cohort. However, mutations in six out of the nine genes can be used to characterize survival (NPMI, IDH1, IDH2, FLT3-ITD, TET2, DNMT3A) and allow for more robust prognostication in the patients who are re-categorized by the IGP model. These mutations should be incorporated into clinical testing for younger patients outside of clinical trials, in order to guide therapy.

We assessed whether expectorated sputum samples are ordered according to national guidelines and the impact of culture results on patient management. Overall, guidelines for ordering sputum samples were followed for 23% (18/78) of patients. Results affected treatment in 18% (14/79) of cases. Reducing inappropriate sputum cultures may have significant economic savings in the hospital system., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Rationale and Objectives: To understand the reasons leading to potentially inappropriate management of imaging findings concerning for malignancy and identify optimal methods for communicating these findings to providers., Materials and Methods: We identified all abdominal imaging examinations with findings of possible cancer performed on six randomly selected days in August to December 2013. Electronic medical records (EMR) of one patient group were reviewed 3 months after the index examination to determine whether management was appropriate (completed follow-up or documented reason for no follow-up) or potentially inappropriate (no follow-up or no documented reason). Providers of a second patient group were contacted 5-6 days after imaging examinations to determine notification preferences., Results: Among 43 patients in the first group, five (12%) received potentially inappropriate management. Reasons included patient loss to follow-up and provider failure to review imaging results, document known imaging findings, or communicate findings to providers outside the health system. Among 16 providers caring for patients in the second group, 33% were unaware of the findings, 75% preferred to be notified of abnormal findings via e-mail or EMR, 56% wanted an embedded hyperlink enabling immediate follow-up order entry, and only 25% had a system to monitor whether patients had completed ordered testing., Conclusions: One in eight patients did not receive potentially necessary follow-up care within 3 months of imaging findings of possible cancer. Automated notification of imaging findings and follow-up monitoring not only is desired by providers but can also address many of the reasons we found for inappropriate management., (Copyright © 2014 AUR. Published by Elsevier Inc. All rights reserved.)

Objective: To determine the component costs of care to optimize treatment with limited resources., Design: We used the Cost-Effectiveness of Preventing AIDS Complications Model of HIV disease and treatment to project life expectancy and both undiscounted and discounted lifetime costs (2010 €)., Methods: We determined medical resource utilization among HIV-infected adults followed from 1998 to 2005 in northern France. Monthly HIV costs were stratified by CD4 cell count. Costs of CD4, HIV RNA and genotype tests and antiretroviral therapy (ART) were derived from published literature. Model inputs from national data included mean age 38 years, mean initial CD4 cell count 372 cells/μl, ART initiation at CD4 cell counts less than 350 cells/μl, and ART regimen costs ranging from €760 to 2570 per month., Results: The model projected a mean undiscounted life expectancy of 26.5 years and a lifetime undiscounted cost of €535,000/patient (€320,700 discounted); 73% of costs were ART related. When patients presented to care with mean CD4 cell counts of 510 cells/μl and initiated ART at CD4 cell counts less than 500 cells/μl or HIV RNA more than 100,000 copies/ml, life expectancy was 27.4 years and costs increased 1-2%, to €546,700 (€324,500 discounted). When we assumed introducing generic drugs would result in a 50% decline in first-line ART costs, lifetime costs decreased 4-6%, to €514,200 (€302 ,800 discounted)., Conclusion: As HIV disease is treated earlier with more efficacious drugs, survival and thus costs of care will continue to increase. The availability in high-income countries of widely used antiretroviral drugs in generic form could reduce these costs.

Background: Our goal was to illustrate a method for making indirect treatment comparisons in the absence of head-to-head trials, by portraying the derivation of published efficacies for prophylaxis regimens of HIV-related opportunistic infections., Results: We identified published results of randomized controlled trials from the United States in which HIV-infected patients received rifabutin, azithromycin, clarithromycin, or placebo for prophylaxis against Mycobacterium avium complex (MAC). We extracted the number of subjects, follow-up time, primary MAC events, mean CD4 count, and proportion of subjects on mono or dual antiretroviral therapy (ART) from each study. We derived the efficacy of each drug using adjusted indirect comparisons and, when possible, by direct comparisons. Five articles satisfied our inclusion criteria. Using direct comparison, we estimated the efficacies of rifabutin, clarithromycin, and azithromycin compared to placebo to be 53% (95% CI, 48-61%), 66% (95% CI, 61-74%), and 66% (95% CI, 60-81%), respectively. Using adjusted indirect calculations, the efficacy of rifabutin compared to placebo ranged from 41% to 44%. The adjusted indirect efficacies of clarithromycin and azithromycin were estimated to be 73% and 72%, respectively., Conclusions: Accurate estimates of specific drug dosages as compared to placebo are important for policy and implementation research. This study illustrates a simple method of adjusting for differences in study populations by using indirect comparisons in the absence of head-to-head HIV clinical trials.

Background: In France, roughly 40,000 HIV-infected persons are unaware of their HIV infection. Although previous studies have evaluated the cost-effectiveness of routine HIV screening in the United States, differences in both the epidemiology of infection and HIV testing behaviors warrant a setting-specific analysis for France., Methods/principal Findings: We estimated the life expectancy (LE), cost and cost-effectiveness of alternative HIV screening strategies in the French general population and high-risk sub-populations using a computer model of HIV detection and treatment, coupled with French national clinical and economic data. We compared risk-factor-based HIV testing ("current practice") to universal routine, voluntary HIV screening in adults aged 18-69. Screening frequencies ranged from once to annually. Input data included mean age (42 years), undiagnosed HIV prevalence (0.10%), annual HIV incidence (0.01%), test acceptance (79%), linkage to care (75%) and cost/test (€43). We performed sensitivity analyses on HIV prevalence and incidence, cost estimates, and the transmission benefits of ART. "Current practice" produced LEs of 242.82 quality-adjusted life months (QALM) among HIV-infected persons and 268.77 QALM in the general population. Adding a one-time HIV screen increased LE by 0.01 QALM in the general population and increased costs by €50/person, for a cost-effectiveness ratio (CER) of €57,400 per quality-adjusted life year (QALY). More frequent screening in the general population increased survival, costs and CERs. Among injection drug users (prevalence 6.17%; incidence 0.17%/year) and in French Guyana (prevalence 0.41%; incidence 0.35%/year), annual screening compared to every five years produced CERs of €51,200 and €46,500/QALY., Conclusions/significance: One-time routine HIV screening in France improves survival compared to "current practice" and compares favorably to other screening interventions recommended in Western Europe. In higher-risk groups, more frequent screening is economically justifiable.

Purpose: ACTG A5164 demonstrated that early antiretroviral therapy (ART) in HIV-infected patients with acute opportunistic infections (OIs) reduced death and AIDS progression compared to ART initiation 1 month later. We project the life expectancies, costs, and incremental cost-effectiveness ratios (ICERs) of these strategies., Method: using an HIV simulation model, we compared 2 strategies for patients with acute OIs: (1) an intervention to deliver early ART, and (2) deferred ART. Parameters from ACTG A5164 included initial mean CD4 count (47/microL), linkage to outpatient care (87%), and immune reconstitution inflammatory syndrome 1 month after ART initiation (7%). The estimated intervention cost was $1,650/patient., Results: early ART lowered projected 1-year mortality from 10.4% to 8.2% and increased life expectancy from 10.07 to 10.39 quality-adjusted life-years (QALYs). Lifetime costs increased from $385,220 with deferred ART to $397,500 with early ART, primarily because life expectancy increased, producing an ICER of $38,600/QALY. Results were most sensitive to increased intervention cost and decreased virologic efficacy in the early ART strategy., Conclusions: an intervention to initiate ART early in patients with acute OIs improves survival and meets US cost-effectiveness thresholds. Programs should be developed to implement this strategy at sites where HIV-infected patients present with OIs.

Background: International trials have shown that CD4+ T-cell-guided structured treatment interruptions (STI) of antiretroviral therapy (ART) lead to worse outcomes than continuous treatment. We simulated continuous ART and STI strategies with higher CD4+ T-cell interruption/reintroduction thresholds than those assessed in actual trials., Methods: Using a model of HIV, we simulated cohorts of African adults with different baseline CD4+ T-cell counts (< or = 200; 201-350; and 351-500 cells/microl). We varied ART initiation criteria (immediate; CD4+ T-cell count < 350 cells/microl or > or = 350 cells/microl with severe HIV-related disease; and CD4+ T-cell count <200 cells/microl or > or = 200 cells/microl with severe HIV-related disease), and ART interruption/reintroduction thresholds (350/250; 500/350; and 700/500 cells/microl). First-line therapy was non-nucleoside reverse transcriptase inhibitor (NNRTI)-based and second-line therapy was protease inhibitor (PI)-based., Results: STI generally reduced life expectancy compared with continuous ART. Life expectancy increased with earlier ART initiation and higher interruption/reintroduction thresholds. STI reduced life expectancy by 48-69 and 11-30 months compared with continuous ART when interruption/reintroduction thresholds were 350/250 and 500/350 cells/microl, depending on ART initiation criteria. When patients interrupted/reintroduced ART at 700/500 cells/microl, life expectancies ranged from 2 months lower to 1 month higher than continuous ART. STI-related life expectancy increased with decreased risk of virological resistance after ART interruptions., Conclusions: STI with NNRTI-based regimens was almost always less effective than continuous treatment, regardless of interruption/reintroduction thresholds. The risks associated with STI decrease only if patients start ART earlier, interrupt/reintroduce treatment at very high CD4+ T-cell thresholds (700/500 cells/microl) and use first-line medications with higher resistance barriers, such as PIs.

Background: The combination of tenofovir and emtricitabine shows promise as HIV preexposure prophylaxis (PrEP). We sought to forecast clinical, epidemiologic, and economic outcomes of PrEP, taking into account uncertainties regarding efficacy, the risks of developing drug resistance and toxicity, behavioral disinhibition, and drug costs., Methods: We adapted a computer simulation of HIV acquisition, detection, and care to model PrEP among men who have sex with men and are at high risk of HIV infection (i.e., 1.6% mean annual incidence of HIV infection) in the United States. Base-case assumptions included 50% PrEP efficacy and monthly tenofovir-emtricitabine costs of $753. We used sensitivity analyses to examine the stability of results and to identify critical input parameters., Results: In a cohort with a mean age of 34 years, PrEP reduced lifetime HIV infection risk from 44% to 25% and increased mean life expectancy from 39.9 to 40.7 years (21.7 to 22.2 discounted quality-adjusted life-years). Discounted mean lifetime treatment costs increased from $81,100 to $232,700 per person, indicating an incremental cost-effectiveness ratio of $298,000 per quality-adjusted life-year gained. Markedly larger reductions in lifetime infection risk (from 44% to 6%) were observed with the assumption of greater (90%) PrEP efficacy. More-favorable incremental cost-effectiveness ratios were obtained by targeting younger populations with a higher incidence of infection and by improvements in the efficacy and cost of PrEP., Conclusions: PrEP could substantially reduce the incidence of HIV transmission in populations at high risk of HIV infection in the United States. Although it is unlikely to confer sufficient benefits to justify the current costs of tenofovir-emtricitabine, price reductions and/or increases in efficacy could make PrEP a cost-effective option in younger populations or populations at higher risk of infection. Given recent disappointments in HIV infection prevention and vaccine development, additional study of PrEP-based HIV prevention is warranted.