Predicting Other Cause Mortality Risk for Older Men with Localized Prostate Cancer: A Dissertation

Background: Overtreatment of localized prostate cancer (PCa) is a concern as many men die of other causes prior to experiencing a treatment benefit. This dissertation characterizes the need for assessing other cause mortality (OCM) risk in older men with PCa and informs efforts to identify patients most likely to benefit from definitive PCa treatment. Methods: Using the linked Surveillance Epidemiology and End Results-Medicare Health Outcomes Survey database, 2,931 men (mean age=75) newly diagnosed with clinical stage T1a-T3a PCa from 1998-2009 were identified. Survival analysis methods were used to compare observed 10-year OCM by primary treatment type. Age and health factors predictive of primary treatment type were assessed with multinomial logistic regression. Predicted mortality estimates from Social Security life tables (recommended for life expectancy evaluation) and two OCM risk estimation tools were compared to observed rates. An improved OCM prediction model was developed fitting Fine and Gray competing risks models for 10-year OCM with age, sociodemographic, comorbidity, activities of daily living, and patient-reported health data as predictors. The tools’ ability to discriminate between patients who died and those who did not was evaluated with Harrell’s c-index (range 0.5-1), which also guided new model selection. Results: Fifty-four percent of older men with localized PCa underwent radiotherapy while 13% underwent prostatectomy. Twenty-three percent of those treated with radiotherapy and 12% of those undergoing prostatectomy experienced OCM within 10 years of treatment and thus were considered overtreated. Health factors indicative of a shorter life expectancy (increased comorbidity, worse physical health, smoking) had little to no association with radiotherapy assignment but were significantly related to reductions in the likelihood of undergoing prostatectomy. Social Security life tables overestimated mortality risk and discriminated poorly between men who died and those who did not over 10 years (c-index=0.59). Existing OCM risk estimation tools were less likely to overestimate OCM rates and had limited but improved discrimination (c-index=0.64). A risk model developed with self-reported age, Charlson comorbidity index score, overall health (excellent-good/fair/poor), smoking, and marital status predictors had improved discrimination (c-index=0.70). Conclusions: Overtreatment of older men with PCa is primarily attributable to radiotherapy and may be reduced by pretreatment assessment of mortality-related health factors. This dissertation provides a prognostic model which utilizes a set of five self-reported characteristics that better identify patients likely to die of OCM within 10 years of diagnosis than age and comorbidity-based assessments alone

The impact of changing guidelines on prostate cancer screening in a population-based setting, 2000-2014

Introduction: This study evaluates the potential impact of the publication of conflicting prostate cancer (PCa) screening trial results in 2009 and changes to the US Preventive Services Task Force (USPSTF) guidelines to recommend against screening in 2012 on temporal trends in PSA testing at two participating sites in the NCI-funded Cancer Research Network. Methods: Study participants were men aged 40-80 without a history of PCa who sought care at Fallon Health (Worcester, MA) or Henry Ford Health System (Detroit, MI) between 2000-2014. We used health claims and electronic health record data to identify men who underwent PSA testing per calendar year. We also examined trends in PSA testing among high-risk men (African-American, family history of PCa). Testing rates were compared between 2000-2008, 2009-2012, and 2013-2014. Results: From a population of 279,350 eligible men, 133,038 (48%) had at least one PSA test during the study period. Mean age at PSA test was 57 years, which increased over time at both sites. Overall, PSA testing rates rose between 2000-2008 (27-32% of eligible men per year), but declined between 2009-2012 (25% of eligible men). Testing rates declined further in 2013-2014 (23% of eligible men). We observed similar rates of decline in testing for men aged 55-69 and those aged ≥70. High-risk men were less likely to be screened across all time periods, although data was limited. Conclusions: This analysis of two population-based electronic health datasets provides evidence of a recent decrease in PSA testing, following an increase in the early 2000s. Although we are unable to determine causality, it is plausible that results of recent screening trials and/or changes to the USPSTF guidelines have impacted PSA testing practices over the past 14 years

Predicting the 10-year risk of death from other causes in men with localized prostate cancer using patient-reported factors: Development of a tool

OBJECTIVE: To develop a tool for estimating the 10-year risk of death from other causes in men with localized prostate cancer. SUBJECTS AND METHODS: We identified 2,425 patients from the Surveillance Epidemiology and End Results-Medicare Health Outcomes Survey database, age \u3c 80, newly diagnosed with clinical stage T1-T3a prostate cancer from 1/1/1998-12/31/2009, with follow-up through 2/28/2013. We developed a Fine and Gray competing-risks model for 10-year other cause mortality considering age, patient-reported comorbid medical conditions, component scores and items of the SF-36 Health Survey, activities of daily living, and sociodemographic characteristics. Model discrimination and calibration were compared to predictions from Social Security life table mortality risk estimates. RESULTS: Over a median follow-up of 7.7 years, 76 men died of prostate-specific causes and 465 died of other causes. The strongest predictors of 10-year other cause mortality risk included increasing age at diagnosis, higher approximated Charlson Comorbidity Index score, worse patient-reported general health (fair or poor vs. excellent-good), smoking at diagnosis, and marital status (all other vs. married) (all p \u3c 0.05). Model discrimination improved over Social Security life tables (c-index of 0.70 vs. 0.59, respectively). Predictions were more accurate than predictions from the Social Security life tables, which overestimated risk in our population. CONCLUSIONS: We provide a tool for estimating the 10-year risk of dying from other causes when making decisions about treating prostate cancer using pre-treatment patient-reported characteristics

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

Identifying associations between diabetes and acute respiratory distress syndrome in patients with acute hypoxemic respiratory failure: an analysis of the LUNG SAFE database

Background: Diabetes mellitus is a common co-existing disease in the critically ill. Diabetes mellitus may reduce the risk of acute respiratory distress syndrome (ARDS), but data from previous studies are conflicting. The objective of this study was to evaluate associations between pre-existing diabetes mellitus and ARDS in critically ill patients with acute hypoxemic respiratory failure (AHRF). Methods: An ancillary analysis of a global, multi-centre prospective observational study (LUNG SAFE) was undertaken. LUNG SAFE evaluated all patients admitted to an intensive care unit (ICU) over a 4-week period, that required mechanical ventilation and met AHRF criteria. Patients who had their AHRF fully explained by cardiac failure were excluded. Important clinical characteristics were included in a stepwise selection approach (forward and backward selection combined with a significance level of 0.05) to identify a set of independent variables associated with having ARDS at any time, developing ARDS (defined as ARDS occurring after day 2 from meeting AHRF criteria) and with hospital mortality. Furthermore, propensity score analysis was undertaken to account for the differences in baseline characteristics between patients with and without diabetes mellitus, and the association between diabetes mellitus and outcomes of interest was assessed on matched samples. Results: Of the 4107 patients with AHRF included in this study, 3022 (73.6%) patients fulfilled ARDS criteria at admission or developed ARDS during their ICU stay. Diabetes mellitus was a pre-existing co-morbidity in 913 patients (22.2% of patients with AHRF). In multivariable analysis, there was no association between diabetes mellitus and having ARDS (OR 0.93 (0.78-1.11); p = 0.39), developing ARDS late (OR 0.79 (0.54-1.15); p = 0.22), or hospital mortality in patients with ARDS (1.15 (0.93-1.42); p = 0.19). In a matched sample of patients, there was no association between diabetes mellitus and outcomes of interest. Conclusions: In a large, global observational study of patients with AHRF, no association was found between diabetes mellitus and having ARDS, developing ARDS, or outcomes from ARDS. Trial registration: NCT02010073. Registered on 12 December 2013

Clinical and policy perspectives on the adoption of active surveillance for low-risk prostate cancer

Comment on: Perceptions of Active Surveillance and Treatment Recommendations for Low-risk Prostate Cancer: Results from a National Survey of Radiation Oncologists and Urologists. [Med Care. 2014

Patient-reported functional health and well-being outcomes with drug therapy: a systematic review of randomized trials using the SF-36 health survey

OBJECTIVES: To evaluate the responsiveness of the SF-36 Health Survey in drug trials and to determine how often clinically efficacious treatments produce meaningful functional health changes across medical conditions. RESEARCH DESIGN: We conducted a systematic review of randomized, double-blind, placebo-controlled drug trials published from 1995 to 2011 that documented results for primary clinical endpoints and SF-36 outcomes. PubMed and a database of SF-36 publications were searched. We evaluated responsiveness as concordance (both statistically significant or both nonsignificant) between primary clinical and SF-36 outcomes. To determine how often SF-36 physical and mental component summary (PCS, MCS) score changes were of meaningful magnitude, mean net of placebo changes with treatment were compared against the developer\u27s recommended 3-point threshold for a minimal important difference (MID) across groups of medical conditions. RESULTS: Of 805 screened trials, 185 met eligibility criteria. Primary clinical and SF-36 outcomes were concordant in 151 trials (82%). Among clinically efficacious trials, 58% reported net mean SF-36 improvements \u3e /=MID threshold; however, SF-36 changes were often modest (PCS IQR, 1.6-4.1; MCS IQR, 0.8-3.5). Variations in treatment impact were apparent across conditions. Clinically efficacious therapies for rheumatoid arthritis, psoriatic arthritis, and psoriasis consistently achieved the largest SF-36 improvements, with 87% exceeding MID, whereas no efficacious therapies for peripheral arterial disease or chronic obstructive pulmonary disease achieved MID threshold. CONCLUSIONS: The SF-36 responds to treatment impact, distinguishing drug therapies that, on average, produce meaningful functional health benefits. Overall, just over half of clinically efficacious trials report meaningful functional health improvements, and results vary widely by medical condition

Assessing health-related quality of life in patients with benign non-toxic goitre

Health-related quality of life (HRQoL) assessments are increasingly used to evaluate treatment effects and to shape the delivery of value based care. Valid generic and disease specific tools are available for quantifying HRQoL in patients with non-toxic goitre. However, few studies have applied these validated instruments to assess HRQoL in patients with benign non-toxic goitre. Limited evidence suggests that patients with non-toxic goitre have HRQoL impairments in multiple HRQoL domains. While the HRQoL-impact of non-toxic goitre may be small relative to other severely disabling medical conditions, treatment is almost exclusively elected for HRQoL indications. Thus better quantification of HRQoL, particularly at better (or more favorable) levels where many patients score, is essential. Web and mobile technologies have eased the ability to deliver surveys to patients. Routine consideration of HRQoL provides the opportunity to monitor the impact of treatment on the outcomes most meaningful for patients and the opportunity to help shape the delivery of value based health care

Prostate-specific antigen testing after the US Preventive Services Task Force recommendation: a population-based analysis of electronic health data

PURPOSE: This study describes longitudinal trends in the use of prostate-specific antigen (PSA)-based testing in two geographically distinct healthcare systems following the 2011 US Preventive Services Task Force (USPSTF) recommendations against routine PSA screening. METHODS: We analyzed population-based health claims data from 253,139 men aged 40-80 who were enrolled at two US healthcare systems. We assessed trends in the percentage of eligible men receiving \u3e/= 1 PSA test per year by time period (2000-2008, 2009-2011, 2012-2014), age (40-54, 55-69, 70-80), and race (white, black, other, unknown), and conducted a joinpoint regression analysis. RESULTS: Men aged 55-69 and 70-80 years of all races had similar use of PSA testing between 2000 and 2011, ranging between 47 and 56% of eligible men by year, while only 22-26% of men aged 40-54 had a PSA test per year during this period. Overall, the percentage of men receiving at least one PSA test per year decreased by 26% between 2009-2011 and 2012-2014, with similar trends across race and age groups. PSA testing declined significantly after 2011 (annual percent change = - 11.28). CONCLUSIONS: Following the 2011 USPSTF recommendations against routine PSA screening, declines in PSA testing were observed among men of all races and across all age groups in two large US healthcare systems

The Impact of Clinical Guidelines on Prostate Cancer Screening Practices in a Population-Based Setting, 2000–2013

Background/Aims: Controversial clinical guidelines have recommended against widespread prostate-specific antigen (PSA) testing, despite evidence suggesting a benefit in certain populations. This study evaluates the impact of the publication of prostate cancer screening trial results in 2009 and changes to the U.S. Preventive Services Task Force (USPSTF) guidelines in 2012 on temporal trends in the use of PSA tests among men 40–80 years old, with follow-up through 2013. Methods: Men aged 40–80 without a history of prostate cancer who sought care at Fallon Health (Meyers Primary Care Institute [MPCI]) or Henry Ford Health System (HFHS) contributed to this analysis. We counted one PSA test per person per calendar year, with rates defined per 1,000 person-years. Men were censored based on prostate cancer diagnosis, PSA test results ≥ 4 ng/mL, disenrollment, death or end of follow-up (Dec. 31, 2014). We also examined trends in PSA testing among high-risk men (African-American, family history of prostate cancer). Test rates were compared among three time periods: 2000–2008, 2009–2012 and 2013–2014. Results: On average, 17,144 men at MPCI and 16,733 men at HFHS had a PSA test each year. Mean age at PSA test was 57 years, which increased over time at both sites. PSA test rates at MPCI declined 33% over the study period from an average of 474 tests/1,000 person-years (2000–2008) to 391/1,000 person-years (2009–2012) to 317/1,000 person-years (2013). At HFHS, PSA test rates rose gradually from 2000 to 2008, with between 30% and 52% of the eligible population (20,838 of 69,550 men in 2000 and 19,366 of 37,434 men in 2008) undergoing ≥ 1 test, followed by a 21% decline from 2008 to 2013 (7,151 of 23,749 men in 2013). At both sites, this decline was attenuated among high-risk men. Conclusion: This analysis of two population-based electronic health datasets provides evidence of decreasing use of PSA testing over time, although high-risk populations experienced a lesser decline. Although we are unable to determine causality, it is plausible that results of recent screening trials and/or restrictive changes to the USPSTF guidelines have impacted PSA testing practices over the past 14 years. As a next step, we will investigate trends in medical follow-up to elevated PSA test results