Upper Extremity Function, Peer Relationships, and Pain Interference: Evaluating the Biopsychosocial Model in a Pediatric Hand Surgery Population Using PROMIS.

PURPOSE: The relationship between biopsychosocial factors and patient-reported function is less clear in pediatric than in adult hand surgery patients. Our primary hypothesis was that pain interference (PI) and peer relationships (PR) would demonstrate association with upper extremity function. Secondarily, we hypothesized that the magnitude of this effect would increase with age. METHODS: Patients aged 5 to 17 years presenting to a tertiary academic clinic between October 2017 and January 2019 were included. The parent/guardian was administered the following instruments after indicating they, rather than the patient, were answering the questions on a tablet computer: Patient-Reported Outcomes Measurement Information System (PROMIS) Upper Extremity (UE) Parent Proxy (PP) Computer Adaptive Test (CAT) v2.0, PROMIS PI PP CAT v2.0, and the PROMIS PR PP CAT v2.0. Ceiling/floor effects and Spearman correlations were calculated. Multivariable Tobit modeling was performed to determine whether biopsychosocial factors and upper extremity function were associated. Multivariable regression coefficients were compared between age cohorts using a separate multivariable model to evaluate the interaction between age and other predictors. RESULTS: Of 139 included participants, the mean age was 11.7 ± 3.7 years and 50% were female. For patients 11 years of age or younger, UE was weakly correlated with PI (coefficient, -0.34; 95% confidence interval, -0.56 to -0.08) and was not correlated with PR. For patients older than 11 years, UE had moderate correlation with PI (coefficient, -0.60; 95% confidence interval, -0.72 to -0.45) and was not correlated with PR. Multivariable analysis demonstrated a significant negative association between PI and UE, with a significantly larger magnitude of effect for patients older than 11 years of age. CONCLUSIONS: The biopsychosocial model applies to pediatric hand surgery patients. The association between greater pain interference and worse patient-reported upper extremity function, as assessed using parent proxy instruments, was significantly stronger for patients older than 11 years than those 11 years old or younger. CLINICAL RELEVANCE: This study suggests that the biopsychosocial model applies to pediatric hand patients.

Sample size allocation in multiregional equivalence studies.

With the increasing globalization of drug development, the multiregional clinical trial (MRCT) has gained extensive use. The data from MRCTs could be accepted by regulatory authorities across regions and countries as the primary sources of evidence to support global marketing drug approval simultaneously. The MRCT can speed up patient enrollment and drug approval, and it makes the effective therapies available to patients all over the world simultaneously. However, there are many challenges both operationally and scientifically in conducting a drug development globally. One of many important questions to answer for the design of a multiregional study is how to partition sample size into each individual region. In this paper, two systematic approaches are proposed for the sample size allocation in a multiregional equivalence trial. A numerical evaluation and a biosimilar trial are used to illustrate the characteristics of the proposed approaches.

Patient navigation for pregnant individuals with opioid use disorder: Results of a randomized multi-site pilot trial.

BACKGROUND AND AIMS: Patient navigation (PN) may benefit pregnant individuals with opioid use disorder (OUD) by improving treatment adherence. We examined participant enrollment, session delivery and assessment feasibility for a PN intervention among pregnant participants and compared PN preliminary effectiveness for OUD treatment engagement with participants in usual care (UC). DESIGN: This study was a pilot single-blinded multi-site randomized trial. SETTING: Two academic medical centers in Pennsylvania (n = 57) and Utah (n = 45), United States participated. PARTICIPANTS: One hundred and two pregnant adult participants unestablished (fewer than 6 weeks) on medication for OUD (MOUD) were randomized to PN (n = 53) or UC (n = 49). INTERVENTION: PN was composed of 10 prenatal sessions (delivered after baseline but before the prenatal assessments) and four postnatal sessions (delivered before the 2- and 6-month postpartum assessments) focused upon OUD treatment and physical/mental health needs. UC involved brief case management. MEASUREMENTS: Feasibility assessments included consent, session delivery and assessment rates. Mixed-effect models for intent-to-treat (ITT) and per protocol (PP, received six or more sessions) populations were estimated to compare outcomes of MOUD use, secondary outcomes of substance use disorder (SUD) treatment attendance and non-prescribed opioid use, and exploratory outcome of overdose at baseline, predelivery and 2 and 6 months postpartum. FINDINGS: We consented 87% (106 of 122) of the proposed target, delivered ~60% of sessions delivered and completed ≥ 75% assessments. PN ITT and PP had better MOUD adherence, SUD treatment attendance, non-prescribed opioid use and overdose outcomes than UC. Notable changes included good evidence for greater percentage change in days for PN PP MOUD use from baseline to 2 months postpartum [PN = 28.0 versus UC = -10.9, 95% confidence interval (CI) = 9.7, 62.1] and some evidence for baseline to 6 months postpartum (PN = 45.4 versus UC = 23.4, 95% CI = -0.7, 48.2). PN PP percentage change in days for SUD treatment attendance also showed good evidence for improvements from baseline to prenatal assessment (PN = 7.4 versus UC = -21.3, 95% CI = 3.3, 53.5). PN compared to UC participants reported fewer overdoses at 2 months (PN = 11.9%/UC = 16.1%) and at 6 months postpartum (PN = 3.8%/UC = 6.2%). CONCLUSIONS: Patient navigation appears to be associated with improvements in opioid use disorder treatment engagement and overdoses during pregnancy. This pilot trial shows the feasibility of the intervention and a future large-scale trial.

Evolution of Phase II Oncology Trial Design: from Single Arm to Master Protocol.

The recent development of novel anticancer treatments with diverse mechanisms of action has accelerated the detection of treatment candidates tremendously. The rapidly changing drug development landscapes and the high failure rates in Phase III trials both underscore the importance of more efficient and robust phase II designs. The goals of phase II oncology studies are to explore the preliminary efficacy and toxicity of the investigational product and to inform future drug development strategies such as go/no-go decisions for phase III development, or dose/indication selection. These complex purposes of phase II oncology designs call for efficient, flexible, and easy-to-implement clinical trial designs. Therefore, innovative adaptive study designs with the potential of improving the efficiency of the study, protecting patients, and improving the quality of information gained from trials have been commonly used in Phase II oncology studies. Although the value of adaptive clinical trial methods in early phase drug development is generally well accepted, there is no comprehensive review and guidance on adaptive design methods and their best practice for phase II oncology trials. In this paper, we review the recent development and evolution of phase II oncology design, including frequentist multistage design, Bayesian continuous monitoring, master protocol design, and innovative design methods for randomized phase II studies. The practical considerations and the implementation of these complex design methods are also discussed.

Cluster analysis to identify patient profiles and substance use patterns among pregnant persons with opioid use disorder.

The study objective was to identify distinct profiles of pregnant persons with opioid use disorder (PP-OUD) using cluster analysis and examine difference in substance use patterns between profiles. We examined data from 104 PP-OUD ≤ 32 weeks of gestation who were recruited into a behavioral health clinical trial at two academic medical centers. We used Partitioning Around Medoids analysis to identify clusters and explored patterns of substance use and substance use treatment between clusters using bivariate statistical tests and regression methods. We identified two distinct clusters of participants, including 'Group A' (n = 68; 65.4 %) and 'Group B' (n = 36; 34.6 %). Group A had fewer members who were not employed (38 % vs 58 %) and incarcerated (3 % vs 8 %) compared to Group B. Group A compared with Group B included more members with: a history of overdose (72 % vs 50 %); anxiety (85 % vs 25 %); ≥moderate pain (76 % vs 22 %); ≥moderate depression (75 % vs 36 %); ≥moderate drug use severity (94 % vs 78 %); and, more days of cannabis (mean: 6.2 vs 2.3 days), stimulant (mean: 4.5 vs 1.3 days), and injection heroin (mean: 1.3 vs 0 days) use in the past 30 days (P < 0.05 for all comparisons). Clusters of PP-OUD differed with respect to sociodemographic characteristics, mental health conditions, and substance use patterns. More research is needed to confirm identified profiles and assess treatment outcomes associated with cluster membership.

Validation of the tobacco, alcohol, prescription medication, and other substance use (TAPS) tool with the WHO alcohol, smoking, and substance Involvement screening test (ASSIST).

INTRODUCTION: Community pharmacies are emerging as a valuable setting to identify patients with substance use. Few tools have been specially validated to screen patients in these settings, particularly among those prescribed opioid medications. The goal of this study was to validate the performance of the Tobacco, Alcohol, Prescription medication, and other Substance use (TAPS) tool in community pharmacy settings compared to a reference-standard substance use assessment. METHODS: Participants were recruited while receiving opioid medications (not solely buprenorphine) from 19 pharmacies from a large national chain in Ohio and Indiana. Adults who were not involved in the criminal justice system or receiving cancer treatment were invited to participate in a one-time, cross-sectional, self-administered, health survey which included the TAPS tool. Substance use risks calculated from the TAPS tool were compared with the reference standard, World Health Organization Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST) using confusion matrices. We calculated Areas Under the Curve (AUC) of Receiver Operating Characteristics Curves (ROC) to evaluate the TAPS tool's validity. RESULTS: The TAPS tool showed fair or better discrimination between moderate-risk use and high-risk use for tobacco, alcohol, and prescription opioids (AUCs: 0.75-0.97 and fair or better discrimination between low-risk and moderate-risk use in five of eight subscales, including tobacco, alcohol, marijuana, stimulants, and heroin (AUCs: 0.70-0.92). CONCLUSION: The TAPS tool detected clinically relevant problem substance use in several drug classes and likely would be a valuable assessment for screening illicit drug use among community pharmacy patients prescribed opioid medications.

Validation and threshold identification of a prescription drug monitoring program clinical opioid risk metric with the WHO alcohol, smoking, and substance involvement screening test.

BACKGROUND: Prescription drug monitoring programs (PDMPs) are critical for pharmacists to identify risky opioid medication use. We performed an independent evaluation of the PDMP-based Narcotic Score (NS) metric. METHODS: This study was a one-time, cross-sectional health assessment within 19 pharmacies from a national chain among adults picking-up opioid medications. The NS metric is a 3-digit composite indicator. The WHO Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST) was the gold-standard to which the NS metric was compared. Machine learning determined optimal risk thresholds; Receiver Operating Characteristic curves and Spearman (P) and Kappa (K) coefficients analyzed concurrent validity. Regression analyses evaluated participant characteristics associated with misclassification. RESULTS: The NS metric showed fair concurrent validity (area under the curve≥0.70; K=0.35; P = 0.37, p < 0.001). The ASSIST and NS metric categorized 37% of participants as low-risk (i.e., not needing screening/intervention) and 32.3% as moderate/high-risk (i.e., needing screening/intervention). Further, 17.2% were categorized as low ASSIST risk but moderate/high NS metric risk, termed false positives. These reported disability (OR=3.12), poor general health (OR=0.66), and/or greater pain severity/interference (OR=1.12/1.09; all p < 0.05; i.e., needing unmanaged-pain screening/intervention). A total of 13.4% were categorized as moderate/high ASSIST risk but low NS metric risk, termed false negatives. These reported greater overdose history (OR=1.24) and/or substance use (OR=1.81-12.66; all p < 0.05). CONCLUSIONS: The NS metric could serve as a useful initial universal prescription opioid-risk screener given its: 1) low-burden (i.e., no direct assessment); 2) high accuracy (86.5%) of actionable data identifying low-risk patients and those needing opioid use/unmanaged pain screening/intervention; and 3) broad availability.

Cost Implications of Varying the Surgical Setting and Anesthesia Type for De Quervain Release Surgery.

Background First extensor compartment release is a common surgical procedure that represents a financial burden to the health care system. Questions/Purposes Study questions included (1) whether surgical encounter costs differ based upon surgical setting (operating room [OR] vs. procedure room [PR]) or (2) based upon anesthesia choice (local only, Bier's block [BB], monitored anesthesia care [MAC], or general [GA]) for De Quervain release (DQR). Patients and Methods Consecutive adult patients undergoing isolated unilateral DQR at a single academic medical center were identified retrospectively by Current Procedural Terminology code (25000). Using our institution's information technology value tools, we calculated total direct costs for each surgical encounter. Costs were adjusted to January 2016 dollars using the Consumer Price Index, normalized using each participant's surgical encounter cost divided by the median cost in the PR group, then compared across each group using Kruskal-Wallis and Nemenyi's post hoc pair-wise tests. Multivariable gamma regression analysis with a log link was performed to identify factors associated with surgical costs. QuickDASH (disabilities of the arm, shoulder, and the hand) scores were compared using a t -test at final follow-up. Results Among 58 included patients, 29% (17/58) were treated in the PR and 71% (41/58) in the OR. Compared with local only in the PR, all other groups were significantly more costly. Multivariable gamma regression indicated that use of OR/BB, OR/MAC, or OR/GA independently led to 211, 222, and 357% greater surgical costs as compared with the PR with local only while controlling for provider and patient age. Furthermore, QuickDASH scores were similar between PR and OR groups at final follow-up. Conclusion Performing DQR in the PR setting under local only anesthesia yields greater value than the OR, as patient-reported outcomes are similar despite significantly lower surgical costs. Level of Evidence This is a Level III, cost analysis study.

Cost Implications of Varying the Surgical Setting and Anesthesia Type for Trigger Finger Release Surgery.

BACKGROUND: Trigger finger release (TFR) is a common surgical procedure, representing a financial burden to the healthcare system. Our null hypothesis is that the choice surgical setting [operating room (OR) versus procedure room (PR)] and anesthetic type [local-only or monitored anesthesia care (MAC)] do not affect surgical encounter costs for TFR. METHODS: Adult patients undergoing isolated unilateral TFR between May 2014 and December 2017 by 5 fellowship-trained hand surgeons at a single academic medical center were identified by Current Procedural Terminology (CPT) code (26055). We excluded patients undergoing revision surgery, tenosynovectomy, or additional procedures. Using our institution's information technology value tools, we calculated total direct costs for each surgical encounter, which were compared between groups. Univariate and multivariable gamma regression were used to model costs. RESULTS: Of 210 included patients, 54% (113/210) of cases were performed in the PR and 46% (97/210) in the OR. No significant differences in demographics were observed between PR and OR groups. Compared to local-only in the PR, the OR with local-only, and OR with MAC, demonstrated 2.2- and 3.2-fold greater median costs. Multivariable models suggested that use of the OR independently led to 221% [95% Confidence interval: 137%-345%; P < 0.01] greater mean costs than the PR, and use of MAC was associated with 30% (95% confidence interval: 13%-49%; P < 0.01) greater mean costs for OR cases than local-only, while controlling for other confounders. CONCLUSION: Performing TFR in the PR setting under local-only anesthesia minimizes surgical encounter direct costs for this common procedure.