Joint modeling and multiple comparisons with the best of data from a SMART with survival outcomes.

A dynamic treatment regimen (DTR) is a sequence of decision rules that can alter treatments or doses based on outcomes from prior treatment. In the case of two lines of treatment, a DTR specifies first-line treatment, and second-line treatment for responders and treatment for non-responders to the first-line treatment. A sequential, multiple assignment, randomized trial (SMART) is one such type of trial that has been designed to assess DTRs. The primary goal of our project is to identify the treatments, covariates, and their interactions result in the best overall survival rate. Many previously proposed methods to analyze data with survival outcomes from a SMART use inverse probability weighting and provide non-parametric estimation of survival rates, but no other information. Other methods have been proposed to identify and estimate the optimal DTR, but inference issues were seldom addressed. We apply a joint modeling approach to provide unbiased survival estimates as a mechanism to quantify baseline and time-varying covariate effects, treatment effects, and their interactions within regimens. The issue of multiple comparisons at specific time points is addressed using multiple comparisons with the best method.

Incidence and predictors of persistent pelvic pain following hysterectomy in women with chronic pelvic pain.

BACKGROUND: Chronic pelvic pain is a debilitating problem that afflicts 15% to 20% of women in the United States. Although more than 200,000 hysterectomies are performed annually for the treatment of chronic pelvic pain, previous studies indicate that 1 in 4 women undergo the discomfort and morbidity of hysterectomy without the relief of pain. The factors that predict treatment failure remain poorly characterized. OBJECTIVE: To describe the incidence of persistent pelvic pain 6 months following hysterectomy in women with chronic pelvic pain and determine whether a simple, self-reported measure of central sensitization is associated with a greater risk of persistent pelvic pain following hysterectomy. STUDY DESIGN: We conducted a prospective, observational cohort study of women undergoing hysterectomy at an academic tertiary care center for a benign indication. Patients with preoperative chronic pelvic pain, defined as average pelvic pain ≥3 on a 0 to 10 numeric rating scale for >3 months before hysterectomy, were included in this analysis. The patients completed validated assessments of pain, anxiety, depression, and centralized pain (using the 2011 Fibromyalgia Survey Criteria, 0-31 points) preoperatively and 6 months after hysterectomy. The demographic information, surgical history, intraoperative findings, and surgical pathology were abstracted from the electronic medical records. Multivariate logistic regression was used to identify the independent predictors of persistent pelvic pain 6 months following hysterectomy, defined as <50% improvement in pelvic pain severity. RESULTS: Among 176 participants with pelvic pain before hysterectomy, 126 (71.6%) were retained at 6 months, and 15 (11.9%) reported persistent pelvic pain. There was no difference in age (P=.46), race (P=.55), average pain severity during menses (P=.68), average overall pelvic pain (P=.10), or pain duration (P=.80) in those with and without persistent pelvic pain. Whereas intraoperative findings of endometriosis (P=.05) and uterine fibroids (P=.03) were associated with a higher incidence of persistent pain on univariate analysis, the surgical route (P=.46), pelvic adhesions (0.51), uterine weight (P=.66), and adenomyosis on histopathology (P=.27) were not related to the risk of persistent pain. Higher preoperative centralized pain scores (P=.01) but not depression (P=.64) or anxiety (P=.45) were more common in women with persistent pelvic pain. Multivariate logistic regression adjusting for age, preoperative pain severity, anxiety, depression, and operative findings of endometriosis and fibroids indicated that every 1-point increase in centralized pain before hysterectomy was associated with a 27% increase in the odds of persistent pelvic pain (odds ratio, 1.27; 95% confidence interval, 1.03-1.57) 6 months after surgery. CONCLUSION: Although the majority of women with chronic pelvic pain report considerable improvement in pain following hysterectomy, higher degrees of centralized pain before hysterectomy is a robust predictor of persistent pelvic pain.

The efficacy of prostate-specific antigen screening: Impact of key components in the ERSPC and PLCO trials.

BACKGROUND: The European Randomized Study of Screening for Prostate Cancer (ERSPC) demonstrated that prostate-specific antigen (PSA) screening significantly reduced prostate cancer mortality (rate ratio, 0.79; 95% confidence interval, 0.69-0.91). The US Prostate, Lung, Colorectal, and Ovarian (PLCO) trial indicated no such reduction but had a wide 95% CI (rate ratio for prostate cancer mortality, 1.09; 95% CI, 0.87-1.36). Standard meta-analyses are unable to account for key differences between the trials that can impact the estimated effects of screening and the trials' point estimates. METHODS: The authors calibrated 2 microsimulation models to individual-level incidence and mortality data from 238,936 men participating in the ERSPC and PLCO trials. A cure parameter for the underlying efficacy of screening was estimated by the models separately for each trial. The authors changed step-by-step major known differences in trial settings, including enrollment and attendance patterns, screening intervals, PSA thresholds, biopsy receipt, control arm contamination, and primary treatment, to reflect a more ideal protocol situation and differences between the trials. RESULTS: Using the cure parameter estimated for the ERSPC, the models projected 19% to 21% and 6% to 8%, respectively, prostate cancer mortality reductions in the ERSPC and PLCO settings. Using this cure parameter, the models projected a reduction of 37% to 43% under annual screening with 100% attendance and biopsy compliance and no contamination. The cure parameter estimated for the PLCO trial was 0. CONCLUSIONS: The observed cancer mortality reduction in screening trials appears to be highly sensitive to trial protocol and practice settings. Accounting for these differences, the efficacy of PSA screening in the PLCO setting is not necessarily inconsistent with ERSPC results. Cancer 2018;124:1197-206. © 2017 American Cancer Society.

Reconciling the Effects of Screening on Prostate Cancer Mortality in the ERSPC and PLCO Trials.

BACKGROUND: The ERSPC (European Randomized Study of Screening for Prostate Cancer) found that screening reduced prostate cancer mortality, but the PLCO (Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial) found no reduction. OBJECTIVE: To evaluate whether effects of screening on prostate cancer mortality relative to no screening differed between the ERSPC and PLCO. DESIGN: Cox regression of prostate cancer death in each trial group, adjusted for age and trial. Extended analyses accounted for increased incidence due to screening and diagnostic work-up in each group via mean lead times (MLTs), which were estimated empirically and using analytic or microsimulation models. SETTING: Randomized controlled trials in Europe and the United States. PARTICIPANTS: Men aged 55 to 69 (ERSPC) or 55 to 74 (PLCO) years at randomization. INTERVENTION: Prostate cancer screening. MEASUREMENTS: Prostate cancer incidence and survival from randomization; prostate cancer incidence in the United States before screening began. RESULTS: Estimated MLTs were similar in the ERSPC and PLCO intervention groups but were longer in the PLCO control group than the ERSPC control group. Extended analyses found no evidence that effects of screening differed between trials (P = 0.37 to 0.47 [range across MLT estimation approaches]) but strong evidence that benefit increased with MLT (P = 0.0027 to 0.0032). Screening was estimated to confer a 7% to 9% reduction in the risk for prostate cancer death per year of MLT. This translated into estimates of 25% to 31% and 27% to 32% lower risk for prostate cancer death with screening as performed in the ERSPC and PLCO intervention groups, respectively, compared with no screening. LIMITATION: The MLT is a simple metric of screening and diagnostic work-up. CONCLUSION: After differences in implementation and settings are accounted for, the ERSPC and PLCO provide compatible evidence that screening reduces prostate cancer mortality. PRIMARY FUNDING SOURCE: National Cancer Institute.

A joint model of cancer incidence, metastasis, and mortality.

Many diseases, especially cancer, are not static, but rather can be summarized by a series of events or stages (e.g. diagnosis, remission, recurrence, metastasis, death). Most available methods to analyze multi-stage data ignore intermediate events and focus on the terminal event or consider (time to) multiple events as independent. Competing-risk or semi-competing-risk models are often deficient in describing the complex relationship between disease progression events which are driven by a shared progression stochastic process. A multi-stage model can only examine two stages at a time and thus fails to capture the effect of one stage on the time spent between other stages. Moreover, most models do not account for latent stages. We propose a semi-parametric joint model of diagnosis, latent metastasis, and cancer death and use nonparametric maximum likelihood to estimate covariate effects on the risks of intermediate events and death and the dependence between them. We illustrate the model with Monte Carlo simulations and analysis of real data on prostate cancer from the SEER database.

Is prostate cancer different in black men? Answers from 3 natural history models.

BACKGROUND: Black men in the United States have substantially higher prostate cancer incidence rates than the general population. The extent to which this incidence disparity is because prostate cancer is more prevalent, more aggressive, and/or more frequently diagnosed in black men is unknown. METHODS: The authors estimated 3 independently developed models of prostate cancer natural history in black men and in the general population using an updated reconstruction of prostate-specific antigen screening, based on the National Health Interview Survey in 2005 and on prostate cancer incidence data from the Surveillance, Epidemiology, and End Results program during 1975 through 2000. By using the estimated models, the natural history of prostate cancer was compared between black men and the general population. RESULTS: The models projected that from 30% to 43% (range across models) of black men develop preclinical prostate cancer by age 85 years, a risk that is (relatively) 28% to 56% higher than that in the general population. Among men who had preclinical disease onset, black men had a similar risk of diagnosis (range, 35%-49%) compared with the general population (32%-44%), but their risk of progression to metastatic disease by the time of diagnosis was from 44% to 75% higher than that in the general population. CONCLUSIONS: Prostate cancer incidence patterns implicate higher incidence of preclinical disease and higher risk of metastatic progression among black men. The findings suggest screening black men earlier than white men and support further research into the benefit-harm tradeoffs of more aggressive screening policies for black men. Cancer 2017;123:2312-2319. © 2017 American Cancer Society.

Semiparametric time-to-event modeling in the presence of a latent progression event.

In cancer research, interest frequently centers on factors influencing a latent event that must precede a terminal event. In practice it is often impossible to observe the latent event precisely, making inference about this process difficult. To address this problem, we propose a joint model for the unobserved time to the latent and terminal events, with the two events linked by the baseline hazard. Covariates enter the model parametrically as linear combinations that multiply, respectively, the hazard for the latent event and the hazard for the terminal event conditional on the latent one. We derive the partial likelihood estimators for this problem assuming the latent event is observed, and propose a profile likelihood-based method for estimation when the latent event is unobserved. The baseline hazard in this case is estimated nonparametrically using the EM algorithm, which allows for closed-form Breslow-type estimators at each iteration, bringing improved computational efficiency and stability compared with maximizing the marginal likelihood directly. We present simulation studies to illustrate the finite-sample properties of the method; its use in practice is demonstrated in the analysis of a prostate cancer data set.

Semiparametric profile likelihood estimation for continuous outcomes with excess zeros in a random-threshold damage-resistance model.

Continuous outcome data with a proportion of observations equal to zero (often referred to as semicontinuous data) arise frequently in biomedical studies. Typical approaches involve two-part models, with one part a logistic model for the probability of observing a zero and some parametric continuous distribution for modeling the positive part of the data. We propose a semiparametric model based on a biological system with competing damage manifestation and resistance processes. This allows us to derive a closed-form profile likelihood based on the retro-hazard function, leading to a flexible procedure for modeling continuous data with a point mass at zero. A simulation study is presented to examine the properties of the method in finite samples. We apply the method to a data set consisting of pulmonary capillary hemorrhage area in lab rats subjected to diagnostic ultrasound. Copyright © 2017 John Wiley & Sons, Ltd.

Evoked Pressure Pain Sensitivity Is Associated with Differential Analgesic Response to Verum and Sham Acupuncture in Fibromyalgia.

OBJECTIVE: Fibromyalgia is a chronic pain condition with few effective treatments. Many fibromyalgia patients seek acupuncture for analgesia; however, its efficacy is limited and not fully understood. This may be due to heterogeneous pathologies among participants in acupuncture clinical trials. We hypothesized that pressure pain tenderness would differentially classify treatment response to verum and sham acupuncture in fibromyalgia patients. DESIGN: Baseline pressure pain sensitivity at the thumbnail at baseline was used in linear mixed models as a modifier of differential treatment response to sham versus verum acupuncture. Similarly, needle-induced sensation was also analyzed to determine its differential effect of treatment on clinical pain. METHODS AND PATIENTS: A cohort of 114 fibromyalgia patients received baseline pressure pain testing and were randomized to either verum (N = 59) or sham (N = 55) acupuncture. Participants received treatments from once a week to three times a week, increasing in three-week blocks for a total of 18 treatments. Clinical pain was measured on a 101-point visual analog scale, and needle sensation was measured by questionnaire throughout the trial. RESULTS: Participants who had higher pain pressure thresholds had greater reduction in clinical pain following verum acupuncture while participants who had lower pain pressure thresholds showed better analgesic response to sham acupuncture. Moreover, patients with lower pressure pain thresholds had exacerbated clinical pain following verum acupuncture. Similar relationships were observed for sensitivity to acupuncture needling. CONCLUSIONS: These findings suggest that acupuncture efficacy in fibromyalgia may be underestimated and a more personalized treatment for fibromyalgia may also be possible.

Joint modeling of time to recurrence and cancer stage at recurrence in oncology trials.

This research was motivated by a clinical trial with bladder cancer patients who went through a surgery and were followed up for cancer recurrence. One of the main objectives of the trial was to evaluate the time to cancer recurrence in patients in control and experimental groups. At the time of recurrence, the disease stage was also evaluated. Because the stage of cancer at recurrence significantly impacts future treatment and patient prognosis of survival, analyzing the time to cancer recurrence and the stage at recurrence jointly provides more clinically relevant information than analyzing the time to recurrence alone. In this paper, we propose a stochastic model for the joint distribution of time to recurrence and cancer stage that (1) accounts for the recurrence caused by cancer cells surviving a treatment or a surgery and for the recurrence caused by spontaneous carcinogenesis, and (2) incorporates parameters that have biological meaning. To estimate the parameters, we use the maximum-likelihood method combined with the EM algorithm. To demonstrate the performance of our modeling, we evaluate the data from a clinical trial in patients with bladder cancer. We also use simulations to assess the sensitivity of the method.

The effect of a translating research into practice intervention to promote use of evidence-based fall prevention interventions in hospitalized adults: A prospective pre-post implementation study in the U.S.

BACKGROUND: Falls are a major public health problem internationally. Many hospitals have implemented fall risk assessment tools, but few have implemented interventions to mitigate patient-specific fall risks. Little research has been done to examine the effect of implementing evidence-based fall prevention interventions to mitigate patient-specific fall risk factors in hospitalized adults. OBJECTIVES: To evaluate the impact of implementing, in 3 U.S. hospitals, evidence-based fall prevention interventions targeted to patient-specific fall risk factors (Targeted Risk Factor Fall Prevention Bundle). Fall rates, fall injury rates, types of fall injuries and adoption of the Targeted Risk Factor Fall Prevention Bundle were compared prior to and following implementation. DESIGN: A prospective pre-post implementation cohort design. SETTING: Thirteen adult medical-surgical units from three community hospitals in the Midwest region of the U.S. PARTICIPANTS: Nurses who were employed at least 20hours/week, provided direct patient care, and licensed as an RN (n=157 pre; 140 post); and medical records of patients 21years of age or older, who received care on the study unit for more than 24hours during the designated data collection period (n=390 pre and post). METHODS: A multi-faceted Translating Research Into Practice Intervention was used to implement the Targeted Risk Factor Fall Prevention Bundle composed of evidence-based fall prevention interventions designed to mitigate patient-specific fall risks. Dependent variables (fall rates, fall injury rates, fall injury type, use of Targeted Risk Factor Fall Prevention Bundle) were collected at baseline, and following completion of the 15month implementation phase. Nurse questionnaires included the Stage of Adoption Scale, and the Use of Research Findings in Practice Scale to measure adoption of evidence-based fall prevention practices. A Medical Record Abstract Form was used to abstract data about use of targeted risk-specific fall prevention interventions. Number of falls, and number and types of fall injuries were collected for each study unit for 3months pre- and post-implementation. Data were analyzed using multivariate analysis. RESULTS: Fall rates declined 22% (p=0.09). Types of fall injuries changed from major and moderate to minor injuries. Fall injury rates did not decline. Use of fall prevention interventions improved significantly (p<0.001) for mobility, toileting, cognition, and risk reduction for injury, but did not change for those targeting medications. CONCLUSIONS: Using the Translating Research Into Practice intervention promoted use of many evidence-based fall prevention interventions to mitigate patient-specific fall risk factors in hospitalized adults.

Semiparametric regression analysis for time-to-event marked endpoints in cancer studies.

In cancer studies the disease natural history process is often observed only at a fixed, random point of diagnosis (a survival time), leading to a current status observation (Sun (2006). The statistical analysis of interval-censored failure time data. Berlin: Springer.) representing a surrogate (a mark) (Jacobsen (2006). Point process theory and applications: marked point and piecewise deterministic processes. Basel: Birkhauser.) attached to the observed survival time. Examples include time to recurrence and stage (local vs. metastatic). We study a simple model that provides insights into the relationship between the observed marked endpoint and the latent disease natural history leading to it. A semiparametric regression model is developed to assess the covariate effects on the observed marked endpoint explained by a latent disease process. The proposed semiparametric regression model can be represented as a transformation model in terms of mark-specific hazards, induced by a process-based mixed effect. Large-sample properties of the proposed estimators are established. The methodology is illustrated by Monte Carlo simulation studies, and an application to a randomized clinical trial of adjuvant therapy for breast cancer.

Fibromyalgia survey criteria are associated with increased postoperative opioid consumption in women undergoing hysterectomy.

BACKGROUND: The current study was designed to test the hypothesis that the fibromyalgia survey criteria would be directly associated with increased opioid consumption after hysterectomy even when accounting for other factors previously described as being predictive for acute postoperative pain. METHODS: Two hundred eight adult patients undergoing hysterectomy between October 2011 and December 2013 were phenotyped preoperatively with the use of validated self-reported questionnaires including the 2011 fibromyalgia survey criteria, measures of pain severity and descriptors, psychological measures, preoperative opioid use, and health information. The primary outcome was the total postoperative opioid consumption converted to oral morphine equivalents. RESULTS: Higher fibromyalgia survey scores were significantly associated with worse preoperative pain characteristics, including higher pain severity, more neuropathic pain, greater psychological distress, and more preoperative opioid use. In a multivariate linear regression model, the fibromyalgia survey score was independently associated with increased postoperative opioid consumption, with an increase of 7-mg oral morphine equivalents for every 1-point increase on the 31-point measure (Estimate, 7.0; Standard Error, 1.7; P < 0.0001). In addition to the fibromyalgia survey score, multivariate analysis showed that more severe medical comorbidity, catastrophizing, laparotomy surgical approach, and preoperative opioid use were also predictive of increased postoperative opioid consumption. CONCLUSIONS: As was previously demonstrated in a total knee and hip arthroplasty cohort, this study demonstrated that increased fibromyalgia survey scores were predictive of postoperative opioid consumption in the posthysterectomy surgical population during their hospital stay. By demonstrating the generalizability in a second surgical cohort, these data suggest that patients with fibromyalgia-like characteristics may require a tailored perioperative analgesic regimen.

Expected population impacts of discontinued prostate-specific antigen screening.

BACKGROUND: Prostate-specific antigen (PSA) screening for prostate cancer has high risks of overdiagnosis, particularly among older men, and reports from screening trials indicate that it saves few lives after 11 to 13 years of follow-up. New clinical guidelines recommend against PSA screening for all men or for men aged >70 years, but, to the authors' knowledge, the expected population effects of these guidelines have not been studied to date. METHODS: Two models of prostate cancer natural history and diagnosis were previously developed using reconstructed PSA screening patterns and prostate cancer incidence in the United States. Assuming a survival benefit of PSA screening consistent with the screening trials, the authors used the models to predict incidence and mortality rates for the period from 2013 through 2025 under continued PSA screening and under discontinued PSA screening for all men or for men aged >70 years. RESULTS: The models predicted that continuation of recent screening rates will overdiagnose 710,000 to 1,120,000 men (range between models) but will avoid 36,000 to 57,000 cancer deaths over the period 2013 through 2025. Discontinued screening for all men eliminated 100% of overdiagnoses but failed to prevent 100% of avoidable cancer deaths. Continued screening for men aged <70 years eliminated 64% to 66% of overdiagnoses but failed to prevent 36% to 39% of avoidable cancer deaths. CONCLUSIONS: Discontinuing PSA screening for all men may generate many avoidable cancer deaths. Continuing PSA screening for men aged <70 years could prevent greater than one-half of these avoidable cancer deaths while dramatically reducing overdiagnoses compared with continued PSA screening for all ages.

Prevalence of the fibromyalgia phenotype in patients with spine pain presenting to a tertiary care pain clinic and the potential treatment implications.

OBJECTIVE: Injections for spinal pain have high failure rates, emphasizing the importance of patient selection. It is possible that detecting the presence of a fibromyalgia (FM)-like phenotype could aid in prediction, because in these individuals a peripheral injection would not address pain due to alterations in central neurotransmission. We undertook this study to test the hypothesis that patients who have spine pain meeting survey criteria for FM would be phenotypically distinct from those who do not. METHODS: We studied 548 patients diagnosed as having primary spine pain. All patients completed validated self-report questionnaires, including the Brief Pain Inventory, the PainDETECT questionnaire, the Hospital Anxiety and Depression Scale, measures of physical function, and the FM criteria and severity scales. RESULTS: Forty-two percent of the patients were FM positive according to the FM criteria and severity scales. Compared with FM-negative patients, FM-positive patients were more likely to be younger, unemployed, and receiving compensation for pain and to have greater pain severity and pain interference and more neuropathic pain descriptors as well as higher levels of depression and anxiety and a lower level of physical function (P < 0.002 for each comparison). Female sex, neuropathic pain, pain interference, and anxiety were independently predictive of FM status in a multivariate analysis (P < 0.01 for all variables). Receiver operating characteristic curve analysis showed a strength of association of 0.80 as measured by the cross-validated C statistic. CONCLUSION: Using the FM criteria and severity scales, we demonstrated profound phenotypic differences in a population of patients with spine pain. Although centralized pain cannot be confirmed with a self-report instrument alone, the pathophysiology of FM may help explain a portion of the variability of responses to spine interventions.

Joint modeling approach for semicompeting risks data with missing nonterminal event status.

Semicompeting risks data, where a subject may experience sequential non-terminal and terminal events, and the terminal event may censor the non-terminal event but not vice versa, are widely available in many biomedical studies. We consider the situation when a proportion of subjects' non-terminal events is missing, such that the observed data become a mixture of "true" semicompeting risks data and partially observed terminal event only data. An illness-death multistate model with proportional hazards assumptions is proposed to study the relationship between non-terminal and terminal events, and provide covariate-specific global and local association measures. Maximum likelihood estimation based on semiparametric regression analysis is used for statistical inference, and asymptotic properties of proposed estimators are studied using empirical process and martingale arguments. We illustrate the proposed method with simulation studies and data analysis of a follicular cell lymphoma study.

Mortality reduction and cumulative excess incidence (CEI) in the prostate-specific antigen (PSA) screening era.

The extent to which PSA screening is related to prostate cancer mortality reduction in the United States (US) is controversial. US Surveillance, Epidemiology, and End Results Program (SEER) data from 1980 to 2016 were examined to assess the relationship between prostate cancer mortality and cumulative excess incidence (CEI) in the PSA screening era and to clarify the impact of race on this relationship. CEI was considered as a surrogate for the intensity of prostate cancer screening with PSA testing and subsequent biopsy as appropriate. Data from 163,982,733 person-years diagnosed with 544,058 prostate cancers (9 registries, 9% of US population) were examined. Strong inverse linear relationships were noted between CEI and prostate cancer mortality, and 317,356 prostate cancer deaths were avoided. Eight regions of the US demonstrated prostate cancer mortality reduction of 46.0-63.7%. On a per population basis, the lives of more black men than white men were saved in three of four registries with sufficient black populations for comparison. Factor(s) independent of CEI (potential effects of treatment advances) explained 14.6% of the mortality benefit (p-value = 0.3357) while there was a significant main effect of CEI (effect = -0.0064; CI: [-0.0088, -0.0040]; p-value < 0.0001). Therefore, there is a strong relationship between CEI and prostate cancer mortality reduction that was not related to factors independent of screening utilization. Minority populations have experienced large mortality reductions in the context of PSA mass utilization.

Statistical modeling of acute and chronic pain patient-reported outcomes obtained from ecological momentary assessment.

ABSTRACT: Ecological momentary assessment (EMA) allows for the collection of participant-reported outcomes (PROs), including pain, in the normal environment at high resolution and with reduced recall bias. Ecological momentary assessment is an important component in studies of pain, providing detailed information about the frequency, intensity, and degree of interference of individuals' pain. However, there is no universally agreed on standard for summarizing pain measures from repeated PRO assessment using EMA into a single, clinically meaningful measure of pain. Here, we quantify the accuracy of summaries (eg, mean and median) of pain outcomes obtained from EMA and the effect of thresholding these summaries to obtain binary clinical end points of chronic pain status (yes/no). Data applications and simulations indicate that binarizing empirical estimators (eg, sample mean, random intercept linear mixed model) can perform well. However, linear mixed-effect modeling estimators that account for the nonlinear relationship between average and variability of pain scores perform better for quantifying the true average pain and reduce estimation error by up to 50%, with larger improvements for individuals with more variable pain scores. We also show that binarizing pain scores (eg, <3 and ≥3) can lead to a substantial loss of statistical power (40%-50%). Thus, when examining pain outcomes using EMA, the use of linear mixed models using the entire scale (0-10) is superior to splitting the outcomes into 2 groups (<3 and ≥3) providing greater statistical power and sensitivity.

Survey criteria for fibromyalgia independently predict increased postoperative opioid consumption after lower-extremity joint arthroplasty: a prospective, observational cohort study.

BACKGROUND: Variance in pain after total knee and hip arthroplasty may be due to a number of procedural and peripheral factors but also, in some individuals, to aberrant central pain processing as is described in conditions like fibromyalgia. To test this hypothesis, the authors conducted a prospective, observational cohort study of patients undergoing lower-extremity joint arthroplasty. METHODS: Five hundred nineteen patients were preoperatively phenotyped using validated self-reported pain questionnaires, psychological measures, and health information. In addition to being assessed for factors previously found to be associated with poor outcomes in arthroplasty, participants also completed the American College of Rheumatology survey criteria for fibromyalgia. Previous studies have suggested that rather than being "present" or "absent," features of fibromyalgia as measured by this instrument, occur over a wide continuum. Postoperative pain control was assessed by total postoperative opioid consumption. RESULTS: Preoperatively, patients with higher fibromyalgia survey scores were younger, more likely to be female, taking more opioids, reported higher pain severity, and had a more negative psychological profile. In the multivariate analysis, the fibromyalgia survey score, younger age, preoperative opioid use, knee (vs. hip), pain severity at baseline, and the anesthetic technique were all predictive of increased postoperative opioid consumption. CONCLUSIONS: The use of the survey criteria for fibromyalgia led to the finding of distinct phenotypic differences, and the measure was independently predictive of opioid consumption. This self-report measure may provide an additional simple means of predicting postoperative pain outcomes and analgesic requirements. Future studies are needed to determine whether tailored therapies can improve postoperative pain control in this population.