Publications

2018
Sebastien Haneuse, Francesca Dominici, Sharon-Lise Normand, and Deborah Schrag. 2018. “Assessment of Between-Hospital Variation in Readmission and Mortality After Cancer Surgical Procedures.” JAMA Netw Open, 1, 6, Pp. e183038.Abstract
Importance: Although current federal quality improvement programs do not include cancer surgery, the Centers for Medicare & Medicaid Services and other payers are considering extending readmission reduction initiatives to include these and other common high-cost episodes. Objectives: To quantify between-hospital variation in quality-related outcomes and identify hospital characteristics associated with high and low performance. Design, Setting, and Participants: This retrospective cohort study obtained data through linkage of the California Cancer Registry to hospital discharge claims databases maintained by the California Office of Statewide Health Planning and Development. All 351 acute care hospitals in California at which 1 or more adults underwent curative intent surgery between January 1, 2007, and December 31, 2011, with analyses finalized July 15, 2018, were included. A total of 138 799 adults undergoing surgery for colorectal, breast, lung, prostate, bladder, thyroid, kidney, endometrial, pancreatic, liver, or esophageal cancer within 6 months of diagnosis, with an American Joint Committee on Cancer stage of I to III at diagnosis, were included. Main Outcomes and Measures: Measures included adjusted odds ratios and variance components from hierarchical mixed-effects logistic regression analyses of in-hospital mortality, 90-day readmission, and 90-day mortality, as well as hospital-specific risk-adjusted rates and risk-adjusted standardized rate ratios for hospitals with a mean annual surgical volume of 10 or more. Results: Across 138 799 patients at the 351 included hospitals, 8.9% were aged 18 to 44 years and 45.9% were aged 65 years or older, 57.4% were women, and 18.2% were nonwhite. Among these, 1240 patients (0.9%) died during the index admission. Among 137 559 patients discharged alive, 19 670 (14.3%) were readmitted and 1754 (1.3%) died within 90 days. After adjusting for patient case-mix differences, evidence of statistically significant variation in risk across hospitals was identified, as characterized by the variance of the random effects in the mixed model, for all 3 metrics (P < .001). In addition, substantial variation was observed in hospital performance profiles: across 260 hospitals with a mean annual surgical volume of 10 or more, 59 (22.7%) had lower-than-expected rates for all 3 metrics, 105 (40.4%) had higher-than-expected rates for 2 of the 3, and 19 (7.3%) had higher-than-expected rates for all 3 metrics. Conclusions and Relevance: Accounting for patient case-mix differences, there appears to be substantial between-hospital variation in in-hospital mortality, 90-day readmission, and 90-day mortality after cancer surgical procedures. Recognizing the multifaceted nature of hospital performance through consideration of mortality and readmission simultaneously may help to prioritize strategies for improving surgical outcomes.
Nicholas S Downing, Changqin Wang, Aakriti Gupta, Yongfei Wang, Sudhakar V Nuti, Joseph S Ross, Susannah M Bernheim, Zhenqiu Lin, Sharon-Lise T Normand, and Harlan M Krumholz. 2018. “Association of Racial and Socioeconomic Disparities With Outcomes Among Patients Hospitalized With Acute Myocardial Infarction, Heart Failure, and Pneumonia: An Analysis of Within- and Between-Hospital Variation.” JAMA Netw Open, 1, 5, Pp. e182044.Abstract
Importance: Although studies have described differences in hospital outcomes by patient race and socioeconomic status, it is not clear whether such disparities are driven by hospitals themselves or by broader systemic effects. Objective: To determine patterns of racial and socioeconomic disparities in outcomes within and between hospitals for patients with acute myocardial infarction, heart failure, and pneumonia. Design, Setting, and Participants: Retrospective cohort study initiated before February 2013, with additional analyses conducted during the peer-review process. Hospitals in the United States treating at least 25 Medicare fee-for-service beneficiaries aged 65 years or older in each race (ie, black and white) and neighborhood income level (ie, higher income and lower income) for acute myocardial infarction, heart failure, and pneumonia between 2009 and 2011 were included. Main Outcomes and Measures: For within-hospital analyses, risk-standardized mortality rates and risk-standardized readmission rates for race and neighborhood income subgroups were calculated at each hospital. The corresponding ratios using intraclass correlation coefficients were then compared. For between-hospital analyses, risk-standardized rates were assessed according to hospitals' proportion of patients in each subgroup. These analyses were performed for each of the 12 analysis cohorts reflecting the unique combinations of outcomes (mortality and readmission), demographics (race and neighborhood income), and conditions (acute myocardial infarction, heart failure, and pneumonia). Results: Between 74% (3545 of 4810) and 91% (4136 of 4554) of US hospitals lacked sufficient racial and socioeconomic diversity to be included in this analysis, with the number of hospitals eligible for analysis varying among cohorts. The 12 analysis cohorts ranged in size from 418 to 1265 hospitals and from 144 417 to 703 324 patients. Within included hospitals, risk-standardized mortality rates tended to be lower among black patients (mean [SD] difference between risk-standardized mortality rates in black patients compared with white patients for acute myocardial infarction, -0.57 [1.1] [P = .47]; for heart failure, -4.7 [1.3] [P < .001]; and for pneumonia, -1.0 [2.0] [P = .05]). However, risk-standardized readmission rates among black patients were higher (mean [SD] difference between risk-standardized readmission rates in black patients compared with white patients for acute myocardial infarction, 4.3 [1.4] [P < .001]; for heart failure, 2.8 [1.8] [P < .001], and for pneumonia, 3.7 [1.3] [P < .001]). Intraclass correlation coefficients ranged from 0.68 to 0.79, indicating that hospitals generally delivered consistent quality to patients of differing races. While the coefficients in the neighborhood income analysis were slightly lower (0.46-0.60), indicating some heterogeneity in within-hospital performance, differences in mortality rates and readmission rates between the 2 neighborhood income groups were small. There were no strong, consistent associations between risk-standardized outcomes for white or higher-income neighborhood patients and hospitals' proportion of black or lower-income neighborhood patients. Conclusions and Relevance: Hospital performance according to race and socioeconomic status was generally consistent within and between hospitals, even as there were overall differences in outcomes by race and neighborhood income. This finding indicates that disparities are likely to be systemic, rather than localized to particular hospitals.
Rohan Khera, Kumar Dharmarajan, Yongfei Wang, Zhenqiu Lin, Susannah M Bernheim, Yun Wang, Sharon-Lise T Normand, and Harlan M Krumholz. 2018. “Association of the Hospital Readmissions Reduction Program With Mortality During and After Hospitalization for Acute Myocardial Infarction, Heart Failure, and Pneumonia.” JAMA Netw Open, 1, 5, Pp. e182777.Abstract
Importance: The US Hospital Readmissions Reduction Program (HRRP) was associated with reduced readmissions among Medicare beneficiaries hospitalized for acute myocardial infarction (AMI), heart failure (HF), and pneumonia. It is important to assess whether there has been a signal for concomitant harm with an increase in mortality. Objective: To evaluate whether the announcement or the implementation of HRRP was associated with an increase in either in-hospital or 30-day postdischarge mortality following hospitalization for AMI, HF, or pneumonia. Design, Setting, and Participants: In this cohort study, using Medicare data, all hospitalizations for AMI, HF, and pneumonia were identified among fee-for-service Medicare beneficiaries aged 65 years and older from January 1, 2006, to December 31, 2014. These were assessed for changes in trends for risk-adjusted rates of in-hospital and 30-day postdischarge mortality after announcement and implementation of the HRRP using an interrupted time series framework. Analyses were done in November 2017 and December 2017. Exposures: Announcement of the HRRP in March 2010, and implementation of its penalties in October 2012. Main Outcomes and Measures: Monthly risk-adjusted rates of in-hospital and 30-day postdischarge mortality. Results: The sample included 1.7 million AMI, 4 million HF, and 3.5 million pneumonia hospitalizations. Between 2006 and 2014, in-hospital mortality decreased for the 3 conditions (AMI, from 10.4% to 9.7%; HF, from 4.3% to 3.5%; pneumonia, from 5.3% to 4.0%) while 30-day postdischarge mortality decreased from 7.4% to 7.0% for AMI (P for trend < .001), but increased from 7.4% to 9.2% for HF (P for trend < .001) and from 7.6% to 8.6% for pneumonia (P for trend < .001). Before the HRRP announcement, monthly postdischarge mortality was stable for AMI (slope for monthly change, 0.002%; 95% CI, -0.001% to 0.006% per month), and increased by 0.004% (95% CI, 0.000% to 0.007%) per month for HF and by 0.005% (95% CI, 0.002% to 0.008%) per month for pneumonia. There were no inflections in slope around HRRP announcement or implementation (P > .05 for all). In contrast, there were significant negative deflections in slopes for readmission rates at HRRP announcement for all conditions. Conclusions and Relevance: Among Medicare beneficiaries, there was no evidence for an increase in in-hospital or postdischarge mortality associated with HRRP announcement or implementation-a period with substantial reductions in readmissions. The improvement in readmission was therefore not associated with any increase in in-hospital or 30-day postdischarge mortality.
Jacob V Spertus and Sharon-Lise T Normand. 2018. “Bayesian propensity scores for high-dimensional causal inference: A comparison of drug-eluting to bare-metal coronary stents.” Biom J.Abstract
High-dimensional data provide many potential confounders that may bolster the plausibility of the ignorability assumption in causal inference problems. Propensity score methods are powerful causal inference tools, which are popular in health care research and are particularly useful for high-dimensional data. Recent interest has surrounded a Bayesian treatment of propensity scores in order to flexibly model the treatment assignment mechanism and summarize posterior quantities while incorporating variance from the treatment model. We discuss methods for Bayesian propensity score analysis of binary treatments, focusing on modern methods for high-dimensional Bayesian regression and the propagation of uncertainty. We introduce a novel and simple estimator for the average treatment effect that capitalizes on conjugacy of the beta and binomial distributions. Through simulations, we show the utility of horseshoe priors and Bayesian additive regression trees paired with our new estimator, while demonstrating the importance of including variance from the treatment regression model. An application to cardiac stent data with almost 500 confounders and 9000 patients illustrates approaches and facilitates comparison with existing alternatives. As measured by a falsifiability endpoint, we improved confounder adjustment compared with past observational research of the same problem.
Nancy L Keating, Haiden A Huskamp, Deborah Schrag, John M McWilliams, Barbara J McNeil, Bruce E Landon, Michael E Chernew, and Sharon-Lise T Normand. 2018. “Diffusion of Bevacizumab Across Oncology Practices: An Observational Study.” Med Care, 56, 1, Pp. 69-77.Abstract
BACKGROUND: Technological advances can improve care and outcomes but are a primary driver of health care spending growth. Understanding diffusion and use of new oncology therapies is important, given substantial increases in prices and spending on such treatments. OBJECTIVES: Examine diffusion of bevacizumab, a novel (in 2004) and high-priced biologic cancer therapy, among US oncology practices during 2005-2012 and assess variation in use across practices. RESEARCH DESIGN: Population-based observational study. SETTING: A total of 2329 US practices providing cancer chemotherapy. PARTICIPANTS: Random 20% sample of 236,304 Medicare fee-for-service beneficiaries aged above 65 years in 2004-2012 undergoing infused chemotherapy for cancer. MEASURES: Diffusion of bevacizumab (cumulative time to first use and 10% use) in practices, variation in use across practices overall and by higher versus lower-value use. We used hierarchical models with practice random effects to estimate the between-practice variation in the probability of receiving bevacizumab and to identify factors associated with use. RESULTS: We observed relatively rapid diffusion of bevacizumab, particularly in independent practices and larger versus smaller practices. We observed substantial variation in use; the adjusted odds ratio (95% confidence interval) of bevacizumab use was 2.90 higher (2.73-3.08) for practices 1 SD above versus one standard deviation below the mean. Variation was less for higher-value [odds ratio=2.72 (2.56-2.89)] than lower-value uses [odds ratio=3.61 (3.21-4.06)]. CONCLUSIONS: Use of bevacizumab varied widely across oncology practices, particularly for lower-value indications. These findings suggest that interventions targeted to practices have potential for decreasing low-value use of high-cost cancer therapies.
Sebastien Haneuse, José Zubizarreta, and Sharon-Lise T Normand. 2018. “Discussion on "Time-dynamic profiling with application to hospital readmission among patients on dialysis," by Jason P. Estes, Danh V. Nguyen, Yanjun Chen, Lorien S. Dalrymple, Connie M. Rhee, Kamyar Kalantar-Zadeh, and Damla Senturk.” Biometrics.
Sherri Rose and Sharon-Lise Normand. 2018. “Double robust estimation for multiple unordered treatments and clustered observations: Evaluating drug-eluting coronary artery stents.” Biometrics.Abstract
Postmarket comparative effectiveness and safety analyses of therapeutic treatments typically involve large observational cohorts. We propose double robust machine learning estimation techniques for implantable medical device evaluations where there are more than two unordered treatments and patients are clustered in hospitals. This flexible approach also accommodates high-dimensional covariates drawn from clinical databases. The Massachusetts Data Analysis Center percutaneous coronary intervention cohort is used to assess the composite outcome of 10 drug-eluting stents among adults implanted with at least one drug-eluting stent in Massachusetts. We find remarkable discrimination between stents. A simulation study designed to mimic this coronary intervention cohort is also presented and produced similar results.
Harlan M Krumholz, Kumar Dharmarajan, and Sharon-Lise T Normand. 2018. “Evaluating Readmission-Need for More Clarity on Methods.” JAMA Cardiol, 3, 3, Pp. 265.
Daniel B Kramer, Sharon-Lise T Normand, Rita Volya, and Laura A Hatfield. 2018. “Facility-Level Variation and Clinical Outcomes in Use of Cardiac Resynchronization Therapy With and Without an Implantable Cardioverter-Defibrillator.” Circ Cardiovasc Qual Outcomes, 11, 12, Pp. e004763.Abstract
BACKGROUND: Little is known about real-world facility-level preferences for cardiac resynchronization therapy devices with (CRT-D) and without (CRT-P) defibrillator backup. We quantify this variation at the facility level and exploit this variation to compare outcomes of patients receiving these 2 devices. METHODS AND RESULTS: Claims data from fee-for-service Medicare beneficiaries were used to identify new CRT-P and CRT-D implants, 2006 to 2012. We modeled factors associated with receipt of each device, and compared mortality, hospitalizations, and reoperations for patients receiving each using both logistic regression and instrumental variable analysis to account for confounding. Among 71 459 device recipients (CRT-P, 11 925; CRT-D, 59 534; 31% women), CRT-P recipients were older, more likely to be women, and had more comorbidities. Variation in device selection among facilities was substantial: After adjustment for patient characteristics, the odds of receiving a CRT-P (versus CRT-D) device were 7.6× higher for a patient treated at a facility in the highest CRT-P use quartile versus a facility in the lowest CRT-P use quartile. Logistic modeling suggested a survival advantage for CRT-D devices but with falsification end points indicating residual confounding. By contrast, in the instrumental variable analysis using facility variability as the proposed instrument, clinical characteristics and falsification end points were well balanced, and 1-year mortality in patients who received CRT-P versus CRT-D implants did not differ, while CRT-P patients had a lower probability of hospitalizations and reoperations in the year following implant. CONCLUSIONS: CRT-P versus CRT-D selection varies substantially among facilities, adjusted for clinical factors. After instrumental variable adjustment for clinical covariates and facility preference, survival was no different between the devices. Therefore, CRT-P may be preferred for Medicare beneficiaries considering new CRT implantation.
Harlan M Krumholz, Sharon-Lise T Normand, and Yun Wang. 2018. “Geographical Health Priority Areas For Older Americans.” Health Aff (Millwood), 37, 1, Pp. 104-110.Abstract
There are wide disparities in health across the US population. The identification of geographic health priority areas for Medicare could inform efforts to eliminate health disparities and improve health care. In a sample of 3,282 counties with more than 73 million unique Medicare beneficiaries in the period 1999-2014, we identified geographical areas-"hot spots"-with persistently higher adjusted mortality rates for older adults compared with the rest of the country. During the study period, the risk-standardized mortality rates decreased from 5.52 percent to 4.61 percent (a 0.91-percentage-point change) for the priority areas and from 5.16 percent to 4.11 percent (a 1.05-percentage-point change) for other areas. Faced with decisions surrounding allocation of scarce resources and marked geographic disparities, the identification and prioritization of hot spots may be one way to eliminate disparities and improve health care.
Paula A Rochon, Andrea Gruneir, Sudeep S Gill, Wei Wu, Lynn Zhu, Nathan Herrmann, Chaim M Bell, Peter C Austin, Nathan M Stall, Lisa McCarthy, Vasily Giannakeas, Amanda Alberga, Dallas P Seitz, Sharon-Lise Normand, Jerry H Gurwitz, and Susan E Bronskill. 2018. “Initial Cholinesterase Inhibitor Therapy Dose and Serious Events in Older Women and Men.” J Am Geriatr Soc.Abstract
OBJECTIVES: To examine dose-related prescribing and short-term serious events associated with initiation of cholinesterase inhibitor (ChEI) therapy. DESIGN: Retrospective, population-based cohort study. SETTING: Ontario, Canada. PARTICIPANTS: Women (n=47,829) and men (n=32,503) aged 66 and older who initiated a ChEI between April 1, 2010, and June 30, 2016. MEASUREMENTS: All-cause serious events (emergency department (ED) visits, inpatient hospitalizations, death) within 30 days of ChEI initiation. Multivariable Cox proportional hazards models were used to estimate adjusted rates of serious events. RESULTS: Overall, 4.8% of older adults were dispensed a lower-than-recommended ChEI starting dose, 87.9% a recommended dose, and 7.3% a higher-than-recommended starting dose. Eight thousand six hundred seventy-one (10.8%) individuals experienced a serious event within 30 days of initiating therapy, primarily ED visits (8,540, 10.6%). Relative to those initiated on a recommended starting dose, those initiated on a higher dose had a significantly increased rate of serious events (women adjusted hazard ratio (aHR) 1.50, 95% confidence interval (CI) =1.38-1.63; men aHR 1.31, 95% CI=1.19-1.45). Similar patterns were found for ED visits and inpatient hospitalizations but not death. The relative effect of higher-than-recommended starting dose dispensed vs. recommended starting dose dispensed was greater in women than it was in men: the number needed to harm was 22 (95% confidence interval (CI)=18-29) for women and 36 (95% CI= 26-61) for men. CONCLUSION: Serious events immediately after initiation of ChEIs were associated with starting ChEI dose. This association was stronger in women.
Xin Zhou, Xiaomei Liao, Lauren M Kunz, Sharon-Lise T Normand, Molin Wang, and Donna Spiegelman. 2018. “A maximum likelihood approach to power calculations for stepped wedge designs of binary outcomes.” Biostatistics.Abstract
In stepped wedge designs (SWD), clusters are randomized to the time period during which new patients will receive the intervention under study in a sequential rollout over time. By the study's end, patients at all clusters receive the intervention, eliminating ethical concerns related to withholding potentially efficacious treatments. This is a practical option in many large-scale public health implementation settings. Little statistical theory for these designs exists for binary outcomes. To address this, we utilized a maximum likelihood approach and developed numerical methods to determine the asymptotic power of the SWD for binary outcomes. We studied how the power of a SWD for detecting risk differences varies as a function of the number of clusters, cluster size, the baseline risk, the intervention effect, the intra-cluster correlation coefficient, and the time effect. We studied the robustness of power to the assumed form of the distribution of the cluster random effects, as well as how power is affected by variable cluster size. % SWD power is sensitive to neither, in contrast to the parallel cluster randomized design which is highly sensitive to variable cluster size. We also found that the approximate weighted least square approach of Hussey and Hughes (2007, Design and analysis of stepped wedge cluster randomized trials. Contemporary Clinical Trials 28, 182-191) for binary outcomes under-estimates the power in some regions of the parameter spaces, and over-estimates it in others. The new method was applied to the design of a large-scale intervention program on post-partum intra-uterine device insertion services for preventing unintended pregnancy in the first 1.5 years following childbirth in Tanzania, where it was found that the previously available method under-estimated the power.
Marsha A Wilcox, Adam J Savitz, Anjené M Addington, Gary S Gray, Eva C Guinan, John W Jackson, Thomas Lehner, Sharon-Lise Normand, Hardeep Ranu, Geetha Senthil, Jake Spertus, Linda Valeri, and Joseph S Ross. 2018. “The Open Translational Science in Schizophrenia (OPTICS) project: an open-science project bringing together Janssen clinical trial and NIMH data.” NPJ Schizophr, 4, 1, Pp. 14.Abstract
Clinical trial data are the gold standard for evaluating pharmaceutical safety and efficacy. There is an ethical and scientific imperative for transparency and data sharing to confirm published results and generate new knowledge. The Open Translational Science in Schizophrenia (OPTICS) Project was an open-science initiative aggregating Janssen clinical trial and NIH/NIMH data from real-world studies and trials in schizophrenia. The project aims were to show the value of using shared data to examine: therapeutic safety and efficacy; disease etiologies and course; and methods development. The success of project investigators was due to collaboration from project applications through analyses, with support from the Harvard Catalyst. Project work was independent of Janssen; all intellectual property was dedicated to the public. Efforts such as this are necessary to gain deeper insights into the biology of disease, foster collaboration, and to achieve the goal of developing better treatments, reducing the overall public health burden of devastating brain diseases.
Jacob Spertus, Marcela Horvitz-Lennon, Haley Abing, and Sharon-Lise Normand. 2018. “Risk of weight gain for specific antipsychotic drugs: a meta-analysis.” NPJ Schizophr, 4, 1, Pp. 12.Abstract
People with schizophrenia are at considerably higher risk of cardiometabolic morbidity than the general population. Second-generation antipsychotic drugs contribute to that risk partly through their weight gain effects, exacerbating an already high burden of disease. While standard 'as-randomized' analyses of clinical trials provide valuable information, they ignore adherence patterns across treatment arms, confounding estimates of realized treatment exposure on outcome. We assess the effect of specific second-generation antipsychotics on weight gain, defined as at least a 7% increase in weight from randomization, using a Bayesian hierarchical model network meta-analysis with individual patient level data. Our data consisted of 14 randomized clinical trials contributing 5923 subjects (mean age = 39 [SD = 12]) assessing various combinations of olanzapine (n = 533), paliperidone (n = 3482), risperidone (n = 540), and placebo (n = 1368). The median time from randomization to dropout or trial completion was 6 weeks (range: 0-60 weeks). The unadjusted probability of weight gain in the placebo group was 4.8% across trials. For each 10 g chlorpromazine equivalent dose increase in olanzapine, the odds of weight gain increased by 5 (95% credible interval: 1.4, 5.3); the effect of risperidone (odds ratio = 1.6 [0.25, 9.1]) was estimated with considerable uncertainty but no different from paliperidone (odds ratio = 1.3 [1.2, 1.5]).
2017
Yan Tang, Marcela Horvitz-Lennon, Walid F Gellad, Judith R Lave, Chung-Chou H Chang, Sharon-Lise Normand, and Julie M Donohue. 6/2017. “Prescribing of Clozapine and Antipsychotic Polypharmacy for Schizophrenia in a Large Medicaid Program.” Psychiatr Serv, 68, 6, Pp. 579-586.Abstract
OBJECTIVE: Underuse of clozapine and overuse of antipsychotic polypharmacy are both indicators of poor quality of care. This study examined variation in prescribing clozapine and antipsychotic polypharmacy across providers, as well as factors associated with these practices. METHODS: Using 2010-2012 Pennsylvania Medicaid data, prescribers were identified if they wrote antipsychotic prescriptions for ten or more nonelderly adult patients with schizophrenia annually. Generalized linear mixed models with a binomial distribution and a logit link were used to examine prescriber-level annual percentages of patients with clozapine use and with long-term (≥90 days) antipsychotic polypharmacy and associated characteristics of prescribers' patient caseloads, prescriber characteristics, and Medicaid payer (fee-for-service versus managed care plans). RESULTS: The study cohort included 645 prescribers in 2010, 632 in 2011, and 650 in 2012. In 2012, the mean prescriber-level annual percentage of patients with any clozapine use was 7% (range 0%-89%), and the mean percentage of patients with any long-term antipsychotic polypharmacy was 7% (range 0%-45%) (similar rates were found during 2010-2012). Prescribers with high prescription volume, a smaller percentage of patients from racial or ethnic minority groups, and a larger percentage of patients eligible for Supplemental Security Income were more likely to use both clozapine and antipsychotic polypharmacy for treating schizophrenia. Prescriber specialty and Medicaid payer were also associated with prescribers' practices. CONCLUSIONS: Considerable variation was found in clozapine and antipsychotic polypharmacy practices across prescribers in their treatment of schizophrenia. Targeting efforts to selected prescribers holds promise as an approach to promote evidence-based antipsychotic prescribing.
Bilal Chughtai, Matthew D Barber, Jialin Mao, James C Forde, Sharon-Lise T Normand, and Art Sedrakyan. 2017. “Association Between the Amount of Vaginal Mesh Used With Mesh Erosions and Repeated Surgery After Repairing Pelvic Organ Prolapse and Stress Urinary Incontinence.” JAMA Surg, 152, 3, Pp. 257-263.Abstract
Importance: Mesh, a synthetic graft, has been used in pelvic organ prolapse (POP) repair and stress urinary incontinence (SUI) to augment and strengthen weakened tissue. Polypropylene mesh has come under scrutiny by the US Food and Drug Administration. Objective: To examine the rates of mesh complications and invasive reintervention after the placement of vaginal mesh for POP repair or SUI surgery. Design, Setting, and Participants: This investigation was an observational cohort study at inpatient and ambulatory surgery settings in New York State. Participants were women who underwent transvaginal repair for POP or SUI with mesh between January 1, 2008, and December 31, 2012, and were followed up through December 31, 2013. They were divided into the following 4 groups based on the amount of mesh exposure: transvaginal POP repair surgery with mesh and concurrent sling use (vaginal mesh plus sling group), transvaginal POP repair with mesh and no concurrent sling use (vaginal mesh group), transvaginal POP repair without mesh but concurrent sling use for SUI (POP sling group), and sling for SUI alone (SUI sling group). Main Outcomes and Measures: The primary outcome was the occurrence of mesh complications and repeated invasive intervention within 1 year after the initial mesh implantation. A time-to-event analysis was performed to examine the occurrence of mesh erosions and subsequent reintervention. Secondary analyses of an age association (<65 vs ≥65 years) were conducted. Results: The study identified 41 604 women who underwent 1 of the 4 procedures. The mean (SD) age of women at their initial mesh implantation was 56.2 (13.0) years. The highest risk of erosions was found in the vaginal mesh plus sling group (2.72%; 95% CI, 2.31%-3.21%) and the lowest in the SUI sling group (1.57%; 95% CI, 1.41%-1.74%). The risk of repeated surgery with concomitant erosion diagnosis was also the highest in the vaginal mesh plus sling group (2.13%; 95% CI, 1.76%-2.56%) and the lowest in the SUI sling group (1.16%; 95% CI, 1.03%-1.31%). Conclusions and Relevance: The combined use of POP mesh and SUI mesh sling was associated with the highest erosion and repeated intervention risk, while mesh sling alone had the lowest erosion and repeated intervention risk. There is evidence for a dose-response relationship between the amount of mesh used and subsequent mesh erosions, complications, and invasive repeated intervention.
Mariana F Lobo, Vanessa Azzone, Frederic S Resnic, Bruno Melica, Armando Teixeira-Pinto, Luís Filipe Azevedo, Alberto Freitas, Cláudia Nisa, Leonor Bacelar-Nicolau, Francisco Nuno Rocha-Gonçalves, José Pereira-Miguel, Altamiro Costa-Pereira, and Sharon-Lise Normand. 2017. “The Atlantic divide in coronary heart disease: Epidemiology and patient care in the US and Portugal.” Rev Port Cardiol, 36, 9, Pp. 583-593.Abstract
INTRODUCTION AND OBJECTIVES: We aimed to compare access to new health technologies to treat coronary heart disease (CHD) in the health systems of Portugal and the US, characterizing the needs of the populations and the resources available. METHODS: We reviewed data for 2000 and 2010 on epidemiologic profiles of CHD and on health care available to patients. Thirty health technologies (16 medical devices and 14 drugs) introduced during the period 1980-2015 were identified by interventional cardiologists. Approval and marketing dates were compared between countries. RESULTS: Relative to the US, Portugal has lower risk profiles and less than half the hospitalizations per capita, but fewer centers per capita provide catheterization and cardiothoracic surgery services. More than 70% of drugs were available sooner in the US, whereas 12 out of 16 medical devices were approved earlier in Portugal. Nevertheless, at least five of these devices were adopted first or diffused faster in the US. Mortality due to CHD and myocardial infarction (MI) was lower in Portugal (CHD: 72.8 vs. 168 and MI: 48.7 vs. 54.1 in Portugal and the US, respectively; age- and gender-adjusted deaths per 100000 population, 2010); but only CHD deaths exhibited a statistically significant difference between the countries. CONCLUSIONS: Differences in regulatory mechanisms and price regulations have a significant impact on the types of health technologies available in the two countries. However, other factors may influence their adoption and diffusion, and this appears to have a greater impact on mortality, due to acute conditions.
Joseph S Ross, Jonathan Bates, Craig S Parzynski, Joseph G Akar, Jeptha P Curtis, Nihar R Desai, James V Freeman, Ginger M Gamble, Richard Kuntz, Shu-Xia Li, Danica Marinac-Dabic, Frederick A Masoudi, Sharon-Lise T Normand, Isuru Ranasinghe, Richard E Shaw, and Harlan M Krumholz. 2017. “Can machine learning complement traditional medical device surveillance? A case study of dual-chamber implantable cardioverter-defibrillators.” Med Devices (Auckl), 10, Pp. 165-188.Abstract
BACKGROUND: Machine learning methods may complement traditional analytic methods for medical device surveillance. METHODS AND RESULTS: Using data from the National Cardiovascular Data Registry for implantable cardioverter-defibrillators (ICDs) linked to Medicare administrative claims for longitudinal follow-up, we applied three statistical approaches to safety-signal detection for commonly used dual-chamber ICDs that used two propensity score (PS) models: one specified by subject-matter experts (PS-SME), and the other one by machine learning-based selection (PS-ML). The first approach used PS-SME and cumulative incidence (time-to-event), the second approach used PS-SME and cumulative risk (Data Extraction and Longitudinal Trend Analysis [DELTA]), and the third approach used PS-ML and cumulative risk (embedded feature selection). Safety-signal surveillance was conducted for eleven dual-chamber ICD models implanted at least 2,000 times over 3 years. Between 2006 and 2010, there were 71,948 Medicare fee-for-service beneficiaries who received dual-chamber ICDs. Cumulative device-specific unadjusted 3-year event rates varied for three surveyed safety signals: death from any cause, 12.8%-20.9%; nonfatal ICD-related adverse events, 19.3%-26.3%; and death from any cause or nonfatal ICD-related adverse event, 27.1%-37.6%. Agreement among safety signals detected/not detected between the time-to-event and DELTA approaches was 90.9% (360 of 396, k=0.068), between the time-to-event and embedded feature-selection approaches was 91.7% (363 of 396, k=-0.028), and between the DELTA and embedded feature selection approaches was 88.1% (349 of 396, k=-0.042). CONCLUSION: Three statistical approaches, including one machine learning method, identified important safety signals, but without exact agreement. Ensemble methods may be needed to detect all safety signals for further evaluation during medical device surveillance.
Abdallah K Alameddine, Paul Visintainer, Sharon-Lise T Normand, Robert E Wolf, and Yvonne A Alameddine. 2017. “Cancer Rates in Adults After Cardiac Interventions: A Preliminary Observational Report.” Am J Clin Oncol, 40, 2, Pp. 122-124.Abstract
BACKGROUND: The postprocedural state after cardiac revascularization interventions is characterized by intense inflammation and activation of inflammatory cytokines due to myonecrosis and ischemia/reperfusion injury. Involvement of similar processes also participates in cellular malignant transformation. In this study, the association between cardiac interventions and subsequent cancer risk development was therefore evaluated. METHODS: The 5-year cumulative incidence of cancer was examined in 2 cardiac care cohorts: all patients undergoing either open heart surgery or percutaneous coronary interventions (PCI) at hospitals in the commonwealth of Massachusetts. The observed cases of cancer were compared with the number of expected cases based on the state cancer rates, adjusting for sex and 5-year age groups. The standardized morbidity ratio (SMR) was used for this comparison. RESULTS: Of 10,301 patients in the surgical cohort, 804 (7.8%) incident cancers developed over 5 years of follow-up, whereas 245.7 incident cancers were expected. This yielded an SMR of 3.27 (95% CI, 3.05-3.51; P<0.0001). In the PCI cohort comprising 13,001 patients, 1029 (7.9%) incident cancers developed over 5 years, resulting in an SMR of 3.53 (95% CI, 3.32-3.75; P<0.0001). Excluding respiratory cancers from the analysis (to limit smoking-related cancers) reduced risk estimates only slightly. For the surgical cohort: SMR=2.80; 95% CI, 2.59-3.01; P<0.0001. For the PCI cohort: SMR=2.97; 95% CI, 2.78-3.18; P<0.0001. CONCLUSIONS: Undergoing heart revascularization procedures was associated with increased rate of cancer development as compared with the state general population. This cohort may warrant increased monitoring.
Zhe Zheng, Heng Zhang, Xin Yuan, Chenfei Rao, Yan Zhao, Yun Wang, Sharon-Lise Normand, Harlan M Krumholz, and Shengshou Hu. 2017. “Comparing Outcomes of Coronary Artery Bypass Grafting Among Large Teaching and Urban Hospitals in China and the United States.” Circ Cardiovasc Qual Outcomes, 10, 6.Abstract
BACKGROUND: Coronary artery disease is prevalent in China, with concomitant increases in the volume of coronary artery bypass grafting (CABG). The present study aims to compare CABG-related outcomes between China and the United States among large teaching and urban hospitals. METHODS AND RESULTS: Observational analysis of patients aged ≥18 years, discharged from acute-care, large teaching and urban hospitals in China and the United States after hospitalization for an isolated CABG surgery. Data were obtained from the Chinese Cardiac Surgery Registry in China and the National Inpatient Sample in the United States. Analysis was stratified by 2 periods: 2007, 2008, and 2010; and 2011 to 2013 periods. The primary outcome was in-hospital mortality, and the secondary outcome was length of stay. The sample included 51 408 patients: 32 040 from 77 hospitals in the China-CABG group and 19 368 from 303 hospitals in the US-CABG group. In the 2007 to 2008, 2010 period and for all-age and aged ≥65 years, the China-CABG group had higher mortality than the US-CABG group (1.91% versus 1.58%, P=0.059; and 3.12% versus 2.20%, P=0.004) and significantly higher age-, sex-, and comorbidity-adjusted odds of death (odds ratio, 1.58; 95% confidential interval, 1.22-2.04; and odds ratio, 1.73; 95% confidential interval, 1.24-2.40). There were no significant mortality differences in the 2011 to 2013 period. For preoperative, postoperative, and total hospital stay, respectively, the median (interquartile range) length of stay across the entire study period between China-CABG and US-CABG groups were 9 (8) versus 1 (3), 9 (6) versus 6 (3), and 20 (12) versus 7 (5) days (all P<0.001). This difference did not change significantly over time. CONCLUSIONS: In 2011 to 2013, there was no significant difference in in-hospital mortality among patients who underwent an isolated CABG surgery in large teaching and urban hospitals in China and the United States. The longer length of stay in China may represent an opportunity for improvement.

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