The burden of significant pain in the cirrhosis population: Risk factors, analgesic use, and impact on health care utilization and clinical outcomes.

BACKGROUND: We aimed to characterize pain and analgesic use in a large contemporary cohort of patients with cirrhosis and to associate pain with unplanned health care utilization and clinical outcomes in this population. METHODS: We included all patients with cirrhosis seen in UCSF hepatology clinics from 2013 to 2020. Pain severity and location were determined using documented pain scores at the initial visit; "significant pain" was defined as moderate or severe using established cutoffs. Demographic, clinical, and medication data were abstracted from electronic medical records. Associations between significant pain and our primary outcome of 1-year unplanned health care utilization (ie, emergency department visit or hospitalization) and our secondary outcomes of mortality and liver transplantation were explored in multivariable models. RESULTS: Among 5333 patients with cirrhosis, 32% had a nonzero pain score at their initial visit and 25% had significant (ie moderate/severe) pain. Sixty percent of patients with significant pain used ≥1 analgesic; 34% used opioids. Patients with cirrhosis with significant pain had similar Model for End-Stage Liver Disease-Sodium scores (14 vs. 13), but higher rates of decompensation (65% vs. 55%). The most common pain location was the abdomen (44%). Patients with abdominal pain, compared to pain in other locations, were more likely to have decompensation (72% vs. 56%). Significant pain was independently associated with unplanned health care utilization (adjusted odds ratio: 1.3, 95% CI: 1.1-1.5) and mortality (adjusted hazard ratio: 1.4, 95% CI: 1.2-1.6). CONCLUSIONS: Pain among patients with cirrhosis is often not well-controlled despite analgesic use, and significant pain is associated with unplanned health care utilization and mortality in this population. Effectively identifying and treating pain are essential in reducing costs and improving quality of life and outcomes among patients with cirrhosis.

Association of state Medicaid expansion policies with pediatric liver transplant outcomes.

Children from minoritized/socioeconomically deprived backgrounds suffer disproportionately high rates of uninsurance and graft failure/death after liver transplant. Medicaid expansion was developed to expand access to public insurance. Our objective was to characterize the impact of Medicaid expansion policies on long-term graft/patient survival after pediatric liver transplantation. All pediatric patients (<19 years) who received a liver transplant between January 1, 2005, and December 31, 2020 in the US were identified in the Scientific Registry of Transplant Recipients (N = 8489). Medicaid expansion was modeled as a time-varying exposure based on transplant and expansion dates. We used Cox proportional hazards models to evaluate the impact of Medicaid expansion on a composite outcome of graft failure/death over 10 years. As a sensitivity analysis, we conducted an intention-to-treat analysis from time of waitlisting to death (N = 1 1901). In multivariable analysis, Medicaid expansion was associated with a 30% decreased hazard of graft failure/death (hazard ratio, 0.70; 95% confidence interval, 0.62, 0.79; P < .001) after adjusting for Black race, public insurance, neighborhood deprivation, and living in a primary care shortage area. In intention-to-treat analyses, Medicaid expansion was associated with a 72% decreased hazard of patient death (hazard ratio, 0.28; 95% confidence interval, 0.23-0.35; P < .001). Policies that enable broader health insurance access may help improve outcomes and reduce disparities for children undergoing liver transplantation.

Assessment of Surgeon Performance of Advanced Open Surgical Skills Using a Microskills-Based Novel Curriculum.

Importance: The increase in minimally invasive surgical procedures has eroded exposure of general surgery residents to open operations. High-fidelity simulation, together with deliberate instruction, is needed for advanced open surgical skill (AOSS) development. Objective: To collect validity evidence for AOSS tools to support a shared model for instruction. Design, Setting, and Participants: This prospective cohort study included postresidency surgeons (PRSs) and second-year general surgery residents (R2s) at a single academic medical center who completed simulated tasks taught within the AOSS curriculum between June 1 and October 31, 2021. Exposures: The AOSS curriculum includes 6 fine-suture and needle handling tasks, including deep suture tying (with and without needles) and continuous suturing using the pitch-and-catch and push-push-pull techniques (both superficial and deep). Teaching and assessment are based on specific microskills using a 3-dimensional printed iliac fossa model. Main Outcomes and Measures: The PRS group was timed and scored (5-point Likert scale) on 10 repetitions of each task. Six months after receiving instruction on the AOSS tasks, the R2 group was similarly timed and scored. Results: The PRS group included 14 surgeons (11 male [79%]; 8 [57%] attending surgeons) who completed the simulation; the R2 group, 9 surgeons (5 female [55%]) who completed the simulation. Score and time variability were greater for the R2s compared with the PRSs for all tasks. The R2s scored lower and took longer on (1) deep pitch-and-catch suturing (69% of maximum points for a mean [SD] of 142.0 [31.7] seconds vs 77% for a mean [SD] of 95.9 [29.4] seconds) and deep push-push-pull suturing (63% of maximum points for a mean [SD] of 284.0 [72.9] seconds vs 85% for a mean [SD] of 141.4 [29.1] seconds) relative to the corresponding superficial tasks; (2) suture tying with a needle vs suture tying without a needle (74% of maximum points for a mean [SD] of 64.6 [19.8] seconds vs 90% for a mean [SD] of 54.4 [15.6] seconds); and (3) the deep push-push-pull vs pitch-and-catch techniques (63% of maximum points for a mean [SD] of 284.0 [72.9] seconds vs 69% of maximum points for a mean [SD] of 142.0 [31.7] seconds). For the PRS group, time was negatively associated with score for the 3 hardest tasks: superficial push-push-pull (ρ = 0.60; P = .02), deep pitch-and-catch (ρ = 0.73; P = .003), and deep push-push-pull (ρ = 0.81; P < .001). For the R2 group, time was negatively associated with score for the 2 easiest tasks: suture tying without a needle (ρ = 0.78; P = .01) and superficial pitch-and-catch (ρ = 0.79; P = .01). Conclusions and Relevance: The findings of this cohort study offer validity evidence for a novel AOSS curriculum; reveal differential difficulty of tasks that can be attributed to specific microskills; and suggest that position on the surgical learning curve may dictate the association between competency and speed. Together these findings suggest specific, actionable opportunities to guide instruction of AOSS, including which microskills to focus on, when individual rehearsal vs guided instruction is more appropriate, and when to focus on speed.

Frailty, mortality, and health care utilization after liver transplantation: From the Multicenter Functional Assessment in Liver Transplantation (FrAILT) Study.

BACKGROUND AND AIMS: Frailty is a well-established risk factor for poor outcomes in patients with cirrhosis awaiting liver transplantation (LT), but whether it predicts outcomes among those who have undergone LT is unknown. APPROACH AND RESULTS: Adult LT recipients from 8 US centers (2012-2019) were included. Pre-LT frailty was assessed in the ambulatory setting using the Liver Frailty Index (LFI). "Frail" was defined by an optimal cut point of LFI ≥ 4.5. We used the 75th percentile to define "prolonged" post-LT length of stay (LOS; ≥12 days), intensive care unit (ICU) days (≥4 days), and inpatient days within 90 post-LT days (≥17 days). Of 1166 LT recipients, 21% were frail pre-LT. Cumulative incidence of death at 1 and 5 years was 6% and 16% for frail and 4% and 10% for nonfrail patients (overall log-rank p = 0.02). Pre-LT frailty was associated with an unadjusted 62% increased risk of post-LT mortality (95% CI, 1.08-2.44); after adjustment for body mass index, HCC, donor age, and donation after cardiac death status, the HR was 2.13 (95% CI, 1.39-3.26). Patients who were frail versus nonfrail experienced a higher adjusted odds of prolonged LT LOS (OR, 2.00; 95% CI, 1.47-2.73), ICU stay (OR, 1.56; 95% CI, 1.12-2.14), inpatient days within 90 post-LT days (OR, 1.72; 95% CI, 1.25-2.37), and nonhome discharge (OR, 2.50; 95% CI, 1.58-3.97). CONCLUSIONS: Compared with nonfrail patients, frail LT recipients had a higher risk of post-LT death and greater post-LT health care utilization, although overall post-LT survival was acceptable. These data lay the foundation to investigate whether targeting pre-LT frailty will improve post-LT outcomes and reduce resource utilization.

Pre-Operative Assessment Tool To Predict Post-operative Pain and Opioid Use in Outpatient Urologic Surgery.

OBJECTIVE: To better understand the pain requirements of urologic patients in the post-operative outpatient setting. Healthcare providers are one of the leading contributors to the current opioid epidemic. Understanding opioid prescribing practices and patients' narcotic requirements while not over-prescribing opioids is a public health priority. METHODS: We conducted a prospective study to examine opioid consumption among adult patients who presented for outpatient urologic surgery at the University of California San Francisco (UCSF) and Zuckerberg San Francisco General (ZSFG) hospitals. We administered a Pre-Operative Pain Requirement Assessment Tool (POPRAT) electronically via text message 3 days prior to surgery to identify objective factors that may predict post-operative pain and opioid requirements. Patients were followed for 7 days post-operatively, in a similar fashion, to assess daily pain, and opioid use. RESULTS: Two hundred and sixty-four participants were eligible for the study and 211 completed the study. Urology patients undergoing outpatient elective procedures used a mean of 5 morphine milligram equivalents (MME) (SD = 14.9) in a 7-day period. Women and patients less than 45 years of age had the highest opioid use. Based on the POPRAT, major predictors of post-operative pain were pre-operative anxiety (0.34 estimate, P value <.001) and anticipated pain (0.34 estimate, P value <.001). Anticipated opioid use, however, did not predict actual opioid use. CONCLUSION: Urologic outpatient surgeries require minimal opioids for pain management. The POPRAT may help identify which patients may experience more pain after surgery. Certain factors such as age and gender may need to be considered when prescribing opioids.

The main factors affecting Taiwan's economic growth rate via dynamic grey relational analysis.

Ever since the grey system theory was proposed about 40 years ago, its characteristics such as small samples, few data, and uncertainty have been used for study in the literature with increasingly wider scope. Recent studies on grey relation analysis have included static data analyses, and most of them have adopted initial values with only a relational order. Under the same study conditions, if different data preprocessing methods are used, then the relational order will be ranked differently. This study took Taiwan as the object to explore seven economic indices (birth rate (%), Taiwan's total population (thousand people), unemployment rate (%), income per capita (USD), weighted average interest rate on deposits (%), Consumer Price Index (CPI), and national income (NI)) and how they affect the economic growth rate. The traditional static grey relational analysis treated the collected data with taking consideration of time effect which is irrational under some circumstance. An innovative dynamic grey relational analysis was carried out by shifting the raw data due to the time leading or lagging effect which is a mean to improve the capability of traditional grey relational analysis. The differences in analyses between static grey relational analysis and dynamic grey relational analysis via different data preprocessing methods were further discussed, finding that different data preprocessing methods generated a new set of relational orders through the latter. Finally, the prosperity index was used to identify the effects of all factors on economic growth (leading, synchronization, and lagging indices).

Functional Status as Measured by Geriatric Assessment Predicts Inferior Survival in Older Allogeneic Hematopoietic Cell Transplantation Recipients.

Allogeneic hematopoietic cell transplantation (alloHCT) has been increasingly offered to older adults with hematologic malignancies. However, optimal methods to determine fitness for alloHCT have yet to be defined. We evaluated the ability of a comprehensive geriatric assessment (CGA) to predict post-alloHCT outcomes in a single-center prospective cohort study of patients age 50 years and older. Outcomes included overall survival (OS), progression-free survival (PFS), and nonrelapse mortality (NRM). A total of 148 patients were included, with a median age of 62 years (range, 50 to 76 years). In multivariate regression analysis, several CGA measures of functional status were predictive of post-alloHCT outcomes, after adjusting for traditional prognostic factors. Any deficit in instrumental activities of daily living (IADL) was associated with inferior OS (hazard ratio [HR], 1.81, 95% confidence interval [CI], 1.07 to 3.08; P = .03) and PFS (HR, 1.85; 95% CI, 1.15 to 2.99; P = .01). A Medical Outcomes Study Physical Health scale (MOS-PH) score <85 was associated with inferior OS (HR, 1.96; 95% CI, 1.13 to 3.40; P = .02), PFS (HR, 1.75; 95% CI, 1.07 to 2.88; P = .03), and increased NRM (subdistribution HR, 2.57; 95% CI, 1.12 to 5.92; P = .03). MOS-PH score was also associated with the number of non-hematologic grade ≥3 adverse events within the first 100 days after alloHCT (rate ratio, 1.61; 95% CI, 1.04 to 2.49; P = .03). These findings support previous work suggesting that IADL is an important prognostic tool prior to alloHCT. MOS-PH is newly identified as an additional metric to identify older patients at higher risk of poor post-alloHCT outcomes, including toxicity and NRM.

Use of integrative medicine approaches for treating adults with sleep disturbances.

AIM: This study determined the prevalence, perceived efficacy, and influencing factors and evaluated the sources of information as well as the barriers and facilitators for the use of integrative medicine approaches (IMA) within the previous 12 months to treat adults with sleep disturbances. BACKGROUND: No studies have assessed the use of integrative medicine approaches in adults with sleep disturbances. METHODS: A cross-sectional postal survey was conducted. Adults with sleep disturbances were purposively selected from the sleep center of a hospital in Taiwan. Binary logistic regression was used to analyze and compare the differences between groups of use and non-use IMA. RESULTS: The response rate was 94.5% (n = 515). The prevalence for the use of integrative medicine approaches was 53.4% (n = 275). The most prevalent IMA was music. However, the most perceivably efficacious integrative medicine approaches was acupressure, followed by music and meditation. Independent explanatory variables were educational attainment, the number of chronic diseases/symptoms, and healthy lifestyles for the use of IMA. The most common source of information was television/radio. The top facilitator and barrier for the use of integrative medicine approaches were side effects of sleeping pills and limited accessibility. CONCLUSIONS: IMA are used by a considerable proportion of adults for treating sleep disturbances in Taiwan. The findings of this study identified the significant explanatory variables of IMA use and provided a fundamental understanding the aspects of IMA use in the adults with sleep disturbances is particularly important for health care providers in practice associated with their patients.

Nonparametric Benefit-Risk Assessment Using Marker Process in the Presence of a Terminal Event.

Benefit-risk assessment is a crucial step in medical decision process. In many biomedical studies, both longitudinal marker measurements and time to a terminal event serve as important endpoints for benefit-risk assessment. The effect of an intervention or a treatment on the longitudinal marker process, however, can be in conflict with its effect on the time to the terminal event. Thus, questions arise on how to evaluate treatment effects based on the two endpoints, for the purpose of deciding on which treatment is most likely to benefit the patients. In this article, we present a unified framework for benefit-risk assessment using the observed longitudinal markers and time to event data. We propose a cumulative weighted marker process to synthesize information from the two endpoints, and use its mean function at a prespecified time point as a benefit-risk summary measure. We consider nonparametric estimation of the summary measure under two scenarios: (i) the longitudinal marker is measured intermittently during the study period, and (ii) the value of the longitudinal marker is observed throughout the entire follow-up period. The large-sample properties of the estimators are derived and compared. Simulation studies and data examples exhibit that the proposed methods are easy to implement and reliable for practical use. Supplemental materials for this article are available online.

Assessment of atherosclerosis in chronic granulomatous disease.

BACKGROUND: Patients with chronic granulomatous disease (CGD) experience immunodeficiency because of defects in the phagocyte NADPH oxidase and the concomitant reduction in reactive oxygen intermediates. This may result in a reduction in atherosclerotic injury. METHODS AND RESULTS: We prospectively assessed the prevalence of cardiovascular risk factors, biomarkers of inflammation and neutrophil activation, and the presence of magnetic resonance imaging and computed tomography quantified subclinical atherosclerosis in the carotid and coronary arteries of 41 patients with CGD and 25 healthy controls in the same age range. Univariable and multivariable associations among risk factors, inflammatory markers, and atherosclerosis burden were assessed. Patients with CGD had significant elevations in traditional risk factors and inflammatory markers compared with control subjects, including hypertension, high-sensitivity C-reactive protein, oxidized low-density lipoprotein, and low high-density lipoprotein. Despite this, patients with CGD had a 22% lower internal carotid artery wall volume compared with control subjects (361.3±76.4 mm(3) versus 463.5±104.7 mm(3); P<0.001). This difference was comparable in p47(phox)- and gp91(phox)-deficient subtypes of CGD and independent of risk factors in multivariate regression analysis. In contrast, the prevalence of coronary arterial calcification was similar between patients with CGD and control subjects (14.6%, CGD; 6.3%, controls; P=0.39). CONCLUSIONS: The observation by magnetic resonance imaging and computerized tomography of reduced carotid but not coronary artery atherosclerosis in patients with CGD despite the high prevalence of traditional risk factors raises questions about the role of NADPH oxidase in the pathogenesis of clinically significant atherosclerosis. Additional high-resolution studies in multiple vascular beds are required to address the therapeutic potential of NADPH oxidase inhibition in cardiovascular diseases. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01063309.

Quantile regression for recurrent gap time data.

Evaluating covariate effects on gap times between successive recurrent events is of interest in many medical and public health studies. While most existing methods for recurrent gap time analysis focus on modeling the hazard function of gap times, a direct interpretation of the covariate effects on the gap times is not available through these methods. In this article, we consider quantile regression that can provide direct assessment of covariate effects on the quantiles of the gap time distribution. Following the spirit of the weighted risk-set method by Luo and Huang (2011, Statistics in Medicine 30, 301-311), we extend the martingale-based estimating equation method considered by Peng and Huang (2008, Journal of the American Statistical Association 103, 637-649) for univariate survival data to analyze recurrent gap time data. The proposed estimation procedure can be easily implemented in existing software for univariate censored quantile regression. Uniform consistency and weak convergence of the proposed estimators are established. Monte Carlo studies demonstrate the effectiveness of the proposed method. An application to data from the Danish Psychiatric Central Register is presented to illustrate the methods developed in this article.

Comparison of resource utilization and clinical outcomes between teaching and nonteaching medical services.

PURPOSE: To compare the resource utilization and clinical outcomes of medical care delivered on general internal medicine inpatient services at teaching and nonteaching services at an academic hospital. METHODS: From February to October 2002, 2189 patients admitted to a 450-bed university-affiliated community hospital were assigned either to a resident-staffed teaching service (n = 1637) or to a hospitalist- or clinic-based internist nonteaching service (n = 552). We compared total hospital costs per patient, length of hospital stay (LOS), hospital readmission within 30 days, in-hospital mortality, and costs for pharmacy, laboratory, radiology, and others between teaching and nonteaching services. RESULTS: Care on a teaching service was not associated with increased overall patient care costs ($5572 vs. $5576; P = .99), LOS (4.92 days vs. 5.10 days; P = .43), readmission rate (12.3% vs. 10.3%; P = .21), or in-hospital mortality (3.7% vs. 4.5%; P = .40). Mean laboratory and radiology costs were higher on the teaching service, but costs for the pharmacy and for speech therapy, occupational therapy, physical therapy, respiratory therapy, pulmonary function testing, and GI endoscopy procedures were not statistically different between the 2 services, and residents did not order more tests or procedures. Case mix and illness severity, as reflected by the distribution of the most frequent DRGs and mean number of secondary diagnoses per patient and DRG-specific LOS, were similar on the 2 services. CONCLUSIONS: At our academic hospital, admission to a general internal medicine teaching service resulted in patient care costs and clinical outcomes comparable to those admitted to a nonteaching service.

Depressive symptoms and learned resourcefulness among Taiwanese female adolescents.

Depression in adolescents is a widespread problem and has negative consequences on mental health, including suicidal tendencies. Worldwide, this condition is twice as prevalent in females as in males. To identify factors that may affect the development of depression in female adolescents in Taiwan, a cross-sectional, correlational design was used to examine the relationships among stressors, learned resourcefulness, and depressive symptoms. Four hundred four Taiwanese female adolescents participated in the study. Descriptive statistics and hierarchical multiple regression were used to analyze data. The study findings suggested that low household income, dissatisfaction with grades, perceived poor health state, and poor peer relationships were significant stressors that contribute to the development of depressive symptoms. Adolescents with greater learned resourcefulness had fewer depressive symptoms. In addition, learned resourcefulness mediated the effects of perceived health and peer relationships on depressive symptoms. Health-care providers can use this knowledge to teach adolescents coping strategies such as use of learned resourcefulness to prevent depression and its negative consequences.

Nonparametric estimation of the bivariate recurrence time distribution.

This article considers statistical models in which two different types of events, such as the diagnosis of a disease and the remission of the disease, occur alternately over time and are observed subject to right censoring. We propose nonparametric estimators for the joint distribution of bivariate recurrence times and the marginal distribution of the first recurrence time. In general, the marginal distribution of the second recurrence time cannot be estimated due to an identifiability problem, but a conditional distribution of the second recurrence time can be estimated non-parametrically. In the literature, statistical methods have been developed to estimate the joint distribution of bivariate recurrence times based on data on the first pair of censored bivariate recurrence times. These methods are inefficient in the model considered here because recurrence times of higher orders are not used. Asymptotic properties of the proposed estimators are established. Numerical studies demonstrate the estimators perform well with practical sample sizes. We apply the proposed method to the South Verona, Italy, psychiatric case register (PCR) data set for illustration of the methods and theory.