Patient Factors Influencing Respiratory-Related Clinician Actions in Chronic Obstructive Pulmonary Disease Screening.

INTRODUCTION: The purpose of this study was to identify patient-related factors that may explain the increased likelihood of receiving a respiratory-related clinician action in patients identified to be at risk for chronic obstructive pulmonary disease in a U.S.-based pragmatic study of chronic obstructive pulmonary disease screening. METHODS: This post hoc analysis (conducted in 2014-2015) of the Screening, Evaluating and Assessing Rate Changes of Diagnosing Respiratory Conditions in Primary Care 1 (SEARCH1) study (conducted in 2010-2011), used the chronic obstructive pulmonary disease Population Screener questionnaire in 112 primary care practices. Anyone with a previous chronic obstructive pulmonary disease diagnosis was excluded. Multivariate logistic regression modeling was used to assess patient factors associated with the likelihood of receiving an respiratory-related clinician action following positive screening. RESULTS: Overall, 994 of 6,497 (15%) screened positive and were considered at risk for chronic obstructive pulmonary disease. However, only 187 of the 994 patients (19%) who screened positive received a respiratory-related clinician action. The chances of receiving a respiratory-related clinician action were significantly increased in patients who visited their physician with a respiratory issue (p<0.05) or had already been prescribed a respiratory medication (p<0.05). Most (81%) patients who screened positive or had a respiratory-related clinician action had one or more comorbidity, including cardiovascular disease (68%), diabetes (30%), depression/anxiety (26%), asthma (11%), and cancer (9%). CONCLUSIONS: Routine chronic obstructive pulmonary disease screening appears to promote respiratory-related clinician actions in patients with a high likelihood for disease who have respiratory complaints or already use prescribed respiratory medication.

Effect of tiotropium on night-time awakening and daily rescue medication use in patients with COPD.

BACKGROUND: Several small studies found night-time awakenings due to COPD symptoms were associated with decreased health status. In this study, night-time awakenings in patients with COPD were examined and effects of tiotropium therapy evaluated. METHODS: This study was a post hoc, exploratory, pooled analysis of twin, multicenter, double-blind, randomized, placebo-controlled, parallel-group trials. Patients with stable moderate-to-severe COPD were randomized to tiotropium HandiHaler® (n = 550) or placebo (n = 371) and followed for 13 weeks. During a 2-week, pre-treatment baseline period and for 13 weeks on treatment, self-reported night-time awakenings due to COPD symptoms, rescue medication (albuterol) use, and morning and evening peak expiratory flow rate (PEFR) were recorded daily. Nightly, COPD-related awakenings were scored: 0 = no awakenings; 1 = 1 awakening; 2 = 2-3 awakenings; or 3 = awake most of the night. Health-related quality-of-life (HRQoL) and energy-fatigue questionnaires were completed at baseline and during treatment. RESULTS: Patients were aged 65.2 ± 8.7 years (mean ± SD), with a mean pre-bronchodilator FEV1 of 36.1 ± 13.5 % predicted normal at baseline. Data for night-time awakenings and albuterol use were available for 543 (99 %) patients on tiotropium and 352 (95 %) on placebo. At baseline, 280 (51.5 %) patients on tiotropium and 179 (50.1 %) on placebo reported ≥1 COPD-related night-time awakening per week. Over the 13-weeks' treatment, tiotropium was associated with fewer night-time awakenings, with mean ± SE overall awakening scores per week of 0.356 ± 0.006 compared with 0.421 ± 0.007 for placebo (p < 0.001); means were significantly lower for tiotropium versus placebo in patients with baseline awakenings (p < 0.001), but not for those without baseline awakenings. COPD-related night-time awakenings were associated with increased nocturnal rescue medication use and lower HRQoL ratings in both treatment arms. Following start of treatment, tiotropium decreased patients' use of rescue medication compared with placebo, and morning and evening adjusted means for PEFR were higher for tiotropium compared with placebo. CONCLUSIONS: Tiotropium is associated with decreased COPD-related night-time awakenings. Night-time awakenings are associated with increased nocturnal rescue medication use and may be a surrogate marker of symptom control in patients with COPD.

Personalized prediction of tumor response and cancer progression on prostate needle biopsy.

PURPOSE: To our knowledge in patients with prostate cancer there are no available tests except clinical variables to determine the likelihood of disease progression. We developed a patient specific, biology driven tool to predict outcome at diagnosis. We also investigated whether biopsy androgen receptor levels predict a durable response to therapy after secondary treatment. MATERIALS AND METHODS: We evaluated paraffin embedded prostate needle biopsy tissue from 1,027 patients with cT1c-T3 prostate cancer treated with surgery and followed a median of 8 years. Machine learning was done to integrate clinical data with biopsy quantitative biometric features. Multivariate models were constructed to predict disease progression with the C index to estimate performance. RESULTS: In a training set of 686 patients (total of 87 progression events) 3 clinical and 3 biopsy tissue characteristics were identified to predict clinical progression within 8 years after prostatectomy with 78% sensitivity, 69% specificity, a C index of 0.74 and a HR of 5.12. Validation in an independent cohort of 341 patients (total of 44 progression events) yielded 76% sensitivity, 64% specificity, a C index of 0.73 and a HR of 3.47. Increased androgen receptor in tumor cells in the biopsy highly significantly predicted resistance to therapy, ie androgen ablation with or without salvage radiotherapy, and clinical failure (p <0.0001). CONCLUSIONS: Morphometry reliably classifies Gleason pattern 3 tumors. When combined with biomarker data, it adds to the hematoxylin and eosin analysis, and prostate specific antigen values currently used to assess outcome at diagnosis. Biopsy androgen receptor levels predict the likelihood of a response to therapy after recurrence and may guide future treatment decisions.

Cost effectiveness of risk-prediction tools in selecting patients for immediate post-prostatectomy treatment.

BACKGROUND AND OBJECTIVE: Ideally, tests that predict the risk of cancer recurrence should be capable of guiding treatment decisions that are both therapeutically effective and cost effective. This paper evaluates the cost effectiveness of two tools that identify patients at high risk for biochemical (prostate-specific antigen) recurrence of prostate cancer after prostatectomy, the hypothesis being that accurate classification of high-risk patients will allow more appropriate use of secondary (adjuvant/salvage) treatment and may improve on current clinical practice. These risk-prediction tools are the Kattan postoperative nomogram, which uses clinicopathologic features, and the Prostate Px test, which employs additional morphometric and immunofluorescence features of the prostate specimen to predict risk of biochemical recurrence. These tools were trained on patients treated at the Memorial Sloan-Kettering Cancer Center (996 patients for the nomogram, 342 patients for the Prostate Px test). METHODS: The cost effectiveness of the Prostate Px test, the Kattan postoperative nomogram, and current clinical practice were compared using a decision analytic model. The modeled treatment for low-risk patients was watchful waiting. The modeled treatments for high-risk patients were local radiation, hormonal therapy, and watchful waiting. Costs, utilities, and transition probabilities were obtained from the literature. Costs and effects were discounted at 3% per year. The time span modeled was 10 years after prostatectomy. Monte Carlo simulation was performed to estimate cost and effectiveness; sensitivity analysis was performed to examine the impact of uncertainty in the parameter values. RESULTS: The expected quality-adjusted life years (QALYs) for the Prostate Px test, nomogram, and current practice were 8.11, 7.39, and 6.47, respectively. The expected costs were $US17 549, $US14 162, and $US14 104, respectively. The incremental cost-effectiveness ratio of the Prostate Px was $US4704/QALY compared with the nomogram, and $US2100/QALY compared with current practice. The incremental cost-effectiveness ratio of the nomogram was $US63/QALY compared with current practice. These ratios are well below the common willingness-to-pay limit of $US50 000/QALY. Expected effectiveness was highest for the Prostate Px test, followed by the nomogram. Expected cost was slightly higher for Prostate Px than for either alternative; nevertheless, the Prostate Px was cost effective compared with both the nomogram and current practice. The nomogram was cost effective compared with current practice. The acceptable cost effectiveness of the Prostate Px test and the nomogram compared with current practice were not sensitive to changes in the values used to inform the model within clinically plausible ranges. The superior performance of both Prostate Px test and nomogram over current practice resulted from identifying high-risk patients likely to benefit from adjuvant treatment, while sparing the low-risk patients the added cost and toxicity of treatment. CONCLUSION: Incorporation of risk-prediction tools in the initial management of patients after prostatectomy resulted in increased QALYs at an acceptable increase in cost relative to current practice.