Population pharmacokinetics of methotrexate and 7-hydroxymethotrexate and delayed excretion in infants and young children with brain tumors.

PURPOSE: The objectives of this study were to develop a population pharmacokinetic model of methotrexate (MTX) and its primary metabolite 7-hydroxymethotrexate (7OHMTX) in children with brain tumors, to identify the sources of pharmacokinetic variability, and to assess whether MTX and 7OHMTX systemic exposures were related to toxicity. METHODS: Patients received 2.5 or 5 g/m2 MTX as a 24-hour infusion and serial samples were analyzed for MTX and 7OHMTX by an LC-MS/MS method. Pharmacokinetic parameters were estimated using nonlinear mixed-effects modeling. Demographics, laboratory values, and genetic polymorphisms were considered as potential covariates to explain the pharmacokinetic variability. Association between MTX and 7OHMTX systemic exposures and MTX-related toxicities were explored using random intercept logistic regression models. RESULTS: The population pharmacokinetics of MTX and 7OHMTX were adequately characterized using two-compartment models in 142 patients (median 1.91 y; age range 0.09 to 4.94 y) in 513 courses. The MTX and 7OHMTX population clearance values were 4.6 and 3.0 l/h/m2, respectively. Baseline body surface area and estimated glomerular filtration rate were significant covariates on both MTX and 7OHMTX plasma disposition. Pharmacogenetic genotypes were associated with MTX pharmacokinetic parameters but had only modest influence. No significant association was observed between MTX or 7OHMTX exposure and MTX-related toxicity. CONCLUSIONS: MTX and 7OHMTX plasma disposition were characterized for the first time in young children with brain tumors. No exposure-toxicity relationship was identified in this study, presumably due to aggressive clinical management which led to a low MTX-related toxicity rate.

Outcomes following intolerance to calcineurin inhibitor-based graft-versus-host disease prophylaxis in children after allogeneic hematopoietic cell transplantation.

Calcineurin inhibitors (CNI), cyclosporine and tacrolimus, are commonly used for pharmacologic prophylaxis of graft-versus-host disease after allogeneic hematopoietic cell transplantation (HCT). Unfortunately, their use is associated with significant toxicities. While intolerance to CNI is well defined, there is very little information on how they impact outcomes after HCT in children. Our retrospective study in a cohort of 82 children shows a high intolerance rate of 39% in this population associated with lower event-free survival and a higher transplant-related mortality.

Pursuing safety in social connection regulates the risk-regulation, social-safety, and behavioral-immune systems.

A new goal-systems model is proposed to help explain when individuals will protect themselves against the risks inherent to social connection. This model assumes that people satisfy the goal to feel included in safe social connections-connections where they are valued and protected rather than at risk of being harmed-by devaluing rejecting friends, trusting in expectancy-consistent relationships, and avoiding infectious strangers. In the hypothesized goal system, frustrating the fundamental goal to feel safe in social connection sensitizes regulatory systems that afford safety from the risk of being interpersonally rejected (i.e., the risk-regulation system), existentially uncertain (i.e., the social-safety system), or physically infected (i.e., the behavioral-immune system). Conversely, fulfilling the fundamental goal to feel safe in social connection desensitizes these self-protective systems. A 3-week experimental daily diary study (N = 555) tested the model hypotheses. We intervened to fulfill the goal to feel safe in social connection by repeatedly conditioning experimental participants to associate their romantic partners with highly positive, approachable words and images. We then tracked how vigilantly experimental versus control participants protected themselves when they encountered social rejection, unexpected behavior, or contagious illness in everyday life. Multilevel analyses revealed that the intervention lessoned self-protective defenses against each of these risks for participants who ordinarily felt most vulnerable to them. The findings provide the first evidence that the fundamental goal to feel safe in social connection can co-opt the risk-regulation, social-safety, and behavioral-immune systems as independent means for its pursuit. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Happiness-To enjoy now or later? Consequences of delaying happiness and living in the moment beliefs.

How do people think about happiness? Is it something best enjoyed as an investment over time, or is it something fleeting that should be savored? When people view happiness as an investment, they may endorse delaying happiness (DH)-the belief that working hard and sacrificing opportunities for happiness now will contribute to greater future happiness. When people view happiness as fleeting, they may endorse living in the moment (LM)-the belief that one should seize proximal opportunities to experience happiness now, rather than later. Using a mix of cross-sectional, meta-analytic (Studies 1, 2a, 2b, 2c), experimental (Study 3), and daily diary methods (Study 4), people who endorsed DH or LM beliefs anticipated more positive affect upon goal attainment and experienced greater well-being, but only DH was related to more negative affect when pursuing nonfocal goals and less delay discounting of future rewards. Implications for self-regulation and emotion are discussed. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

I'm Still Spending: Financial Contingency of Self-Worth Predicts Financial Motivational Conflict and Compulsive Buying.

People with financially contingent self-worth (FCSW) base their self-esteem on money and feel pressured to achieve financial success. However, the present research suggests such individuals may be vulnerable to compulsive buying and experiencing distress and impairment in their lives from engaging in this maladaptive behavior (Study 1a-1b). Study 2 identified a key mechanism: People with FCSW experience more motivational conflict between wanting to spend (vs. not spend) their money, which predicts greater compulsive buying intentions and anticipated distress from making excessive purchases. A 5-week diary study revealed that FCSW-on average and at a weekly level-predicted greater perceived financial motivational conflict and more compulsive buying, distress, and impairment in life (Study 3). People with FCSW experience more financial motivational conflict, independent of beliefs about spending implying wealth or feeling pressured to spend to display one's wealth to others (Study 4). Implications and future directions are discussed.

Human Astrovirus VA1 Encephalitis in Pediatric Patients With Cancer: Report of 2 Cases and Review of the Literature.

Novel human astroviruses (HAstVs) have recently been implicated as rare causes of fatal encephalitis in immunocompromised patients, for which there is no proven treatment. We report 2 cases from our institution in which HAstV-VA1 was detected in the cerebrospinal fluid by metagenomic next-generation sequencing after the initial evaluation revealed no etiology.

Chronic pain treatment preferences change following participation in N-of-1 trials, but not always in the expected direction.

OBJECTIVE: To examine pain treatment preferences before and after participation in an N-of-1 trial. STUDY DESIGN AND SETTING: In this observational study nested within a randomized trial, we examined chronic pain patients' preferences before and after treatment in relation to N-of-1 trial results; assessed the influence of different schemes for defining comparative "superiority" on potential conclusions; and generated classification trees illustrating the relationship between pre-treatment preferences, N-of-1 trial results, and post-treatment preferences. RESULTS: Treatment preferences differed pre- and post-trial for 40% of participants. The proportion of patients whose N-of-1 trials demonstrated "superiority" of one treatment regimen over the other varied depending on how superiority was defined and ranged from 24% (using criteria that required statistically significant differences between regimens) to 62% (when relying only on differences in point estimates). Regardless of criteria for declaring treatment superiority, nearly three-fourths of patients with equivocal N-of-1 trial results nevertheless expressed definite preferences post-trial. CONCLUSION: A large segment of patients undergoing N-of-1 trials for chronic pain altered their treatment preferences. However, the direction of preference change did not necessarily correspond to the N-of-1 results. More research is needed to understand how patients use N-of-1 trial results, why preferences are "sticky" even in the face of personalized data, and how patients and clinicians might be educated to use N-of-1 trial results more informatively.

Treatment of Pediatric Adrenocortical Carcinoma With Surgery, Retroperitoneal Lymph Node Dissection, and Chemotherapy: The Children's Oncology Group ARAR0332 Protocol.

PURPOSE: Adrenocortical carcinoma (ACC) is a rare aggressive pediatric malignancy with distinct biology. Its treatment follows the principles developed for adults; pediatric-specific studies are scarce. PATIENTS AND METHODS: Prospective single-arm risk-stratified interventional study. Study objectives were (1) to describe the outcome of patients with stage I ACC treated with adrenalectomy alone; (2) to describe the outcome of stage II patients (completely resected > 200 cc or > 100 g) treated with adrenalectomy and retroperitoneal lymph node dissection; and (3) to describe the outcome of patients with stage III or IV treated with mitotane and chemotherapy. RESULTS: Between September 2006 and May 2013, 78 patients (77 eligible, 51 females) were enrolled. The 5-year event-free survival estimates for stages I (24 patients), II (15 patients), III (24 patients), and IV (14 patients) were 86.2%, 53.3%, 81%, and 7.1%, respectively. The corresponding 5-year overall survival estimates were 95.2%, 78.8%, 94.7%, and 15.6%, respectively. On univariate analysis, age, stage, presence of virilization, Cushing syndrome, or hypertension, germline TP53 status, and presence of a somatic ATRX mutation were associated with outcome. On multivariable analysis, only stage and age were significantly associated with outcome. The probabilities of mitotane and chemotherapy feasibility events were 10.5% and 31.6%, respectively. CONCLUSION: Outcome for children with stage I ACC is excellent with surgery. Outcome for patients with stage II disease is inferior despite retroperitoneal lymph node dissection. Patients with stage III ACC have an excellent outcome combining surgery and chemotherapy. Patients with stage IV ACC are older and have a poor outcome; new treatments should be explored for this high-risk group. The combination of mitotane and chemotherapy as prescribed in ARAR0332 resulted in significant toxicity; one third of patients with advanced disease could not complete the scheduled treatment.

Is satisficing really satisfying? Satisficers exhibit greater threat than maximizers during choice overload.

When selecting from too many options (i.e., choice overload), maximizers (people who search exhaustively to make decisions that are optimal) report more negative post-decisional evaluations of their choices than do satisficers (people who search minimally to make decisions that are sufficient). Although ample evidence exists for differences in responses after-the-fact, little is known about possible divergences in maximizers' and satisficers' experiences during choice overload. Thus, using the biopsychosocial model of challenge/threat, we examined 128 participants' cardiovascular responses as they actively made a selection from many options. Specifically, we focused on cardiovascular responses assessing the degree to which individuals (a) viewed their decisions as valuable/important and (b) viewed themselves as capable (vs. incapable) of making a good choice. Although we found no differences in terms of the value individuals placed on their decisions (i.e., cardiovascular responses of task engagement), satisficers-compared to maximizers-exhibited cardiovascular responses consistent with feeling less capable of making their choice (i.e., greater relative threat). The current work provides a novel investigation of the nature of differences in maximizers'/satisficers' momentary choice overload experiences, suggesting insight into why they engage in such distinct search behaviors.

Facing the Facets: No Association Between Dispositional Mindfulness Facets and Positive Momentary Stress Responses During Active Stressors.

Mindfulness has been associated with enhanced coping with stress. However, it remains unclear how dispositional mindfulness impacts the nature and valence of experiences during active stressors. Across 1,001 total participants, we used cardiovascular responses from the biopsychosocial model of challenge/threat to assess the degree to which individuals cared about a stressor in the moment and had a positive versus negative psychological experience. Although we found a small association between mindfulness-particularly the acting with awareness facet-and responses consistent with caring more about the stressor (i.e., greater task engagement), we found no evidence that mindfulness was associated with exhibiting a more positive psychological response (i.e., greater challenge) during the stressor. Despite no differences in the valence of momentary experiences as a function of mindfulness, individuals higher in mindfulness self-reported more positive experiences afterward. These findings suggest that dispositional mindfulness may benefit responses to active stressors only after they have passed.

Evaluation of a learning collaborative to advance team-based care in Federally Qualified Health Centers.

Practising team-based primary care allows Federally Qualified Health Centers (FQHC) in the USA to be accredited as patient-centred medical homes, positioning them for value-based models of shared savings in healthcare costs. Team-based care (TBC) involves redesign of staff roles and care delivery processes to improve efficiency and effectiveness, which requires a systematic and supportive approach to practice change over time. Thirteen FQHC primary care teams participated in an 8-month learning collaborative with a goal of providing teams with the knowledge, skills and coaching support needed to advance TBC in their organisations. The primary aim was to evaluate self-reported changes in FQHC teams' assessment of their practice relative to key concepts of TBC. The secondary aim was to evaluate how teams used the collaborative to develop new skills to advance TBC, and the implementation, service and patient outcomes they achieved. Site visits were conducted with three teams 6 months postcollaborative. Results: Two teams withdrew. The remaining teams embarked on 15 TBC improvement initiatives. Nine teams submitted a total of 11 playbooks to guide other staff in changes to their practice. Three teams reported improved efficiencies at the service level (screening and scheduling), and one improved outcomes in patients with diabetes. The nine teams that completed precollaborative and postcollaborative self-assessments reported improvements in their practice and in coach and team skills. Site visits revealed that actionable data were a barrier to improvement, coaching support from the collaborative was highly valued and FQHC leadership support was critical to improvement. Leadership investment in developing their primary care teams' quality improvement, coaching and data analytical skills can advance TBC in their organisations.

Activity of Vincristine and Irinotecan in Diffuse Anaplastic Wilms Tumor and Therapy Outcomes of Stage II to IV Disease: Results of the Children's Oncology Group AREN0321 Study.

PURPOSE: AREN0321 evaluated the activity of vincristine and irinotecan (VI) in patients with newly diagnosed diffuse anaplastic Wilms tumor (DAWT) and whether a regimen containing carboplatin (regimen UH1) in addition to regimen I agents used in the National Wilms Tumor Study 5 (NWTS-5; vincristine, doxorubicin, cyclophosphamide, and etoposide plus radiotherapy) would improve patient outcomes. PATIENTS AND METHODS: Patients with stage II to IV DAWT without measurable disease received regimen UH1. Patients with stage IV measurable disease were eligible to receive VI (vincristine, 1.5 mg/m2 per day intravenously on days 1 and 8; irinotecan, 20 mg/m2 per day intravenously on days 1-5 and 8-12 of a 21-day cycle) in an upfront window; those with complete (CR) or partial response (PR) had VI incorporated into regimen UH1 (regimen UH2). The study was designed to detect improvement in outcomes of patients with stage II to IV DAWT compared with historical controls treated with regimen I. RESULTS: Sixty-six eligible patients were enrolled. Of 14 patients with stage IV measurable disease who received VI, 11 (79%) achieved CR (n = 1) or PR (n = 10) after 2 cycles. Doses of doxorubicin, cyclophosphamide, and etoposide were reduced midstudy because of nonhematologic toxicity. Four patients (6%) died as a result of toxicity. Four-year event-free survival, relapse-free survival, and overall survival rates were 67.7% (95% CI, 55.9% to 79.4%), 72.9% (95% CI, 61.5% to 84.4%), and 73.7% (95% CI, 62.7% to 84.8%), respectively, compared with 57.5% (95% CI, 47.6% to 67.4%; P = .26), 57.5% (95% CI, 47.6% to 67.4%; P = .048), and 59.2% (95% CI, 49.4% to 69.0%; P = .08), respectively, in NWTS-5. CONCLUSION: VI produced a high response rate in patients with metastatic DAWT. AREN0321 treatment seemed to improve outcomes for patients with stage II to IV DAWT compared with NWTS-5, but with increased toxicity. The UH2 regimen warrants further investigation with modifications to reduce toxicity.

Can't Buy Me Love (or Friendship): Social Consequences of Financially Contingent Self-Worth.

Although people may think that money improves one's relationships, research suggests otherwise. Focusing on money is associated with spending less time maintaining relationships and less desire to rely on others for help. But why does focusing on money relate to worse social outcomes? We propose that when people base their self-esteem on financial success-that is, have financially contingent self-worth-they are likely to feel pressured to pursue success in this domain, which may come at the expense of spending time with close others. Consistent with this idea, results of four cross-sectional studies (N = 2,439) and a daily diary study (N = 246) revealed that basing one's self-worth on financial success is associated with greater feelings of loneliness and social disconnection, and this may be related to experiencing less autonomy and spending less time with family and friends.

Effect of Mobile Device-Assisted N-of-1 Trial Participation on Analgesic Prescribing for Chronic Pain: Randomized Controlled Trial.

OBJECTIVES: Opioids and non-steroidal anti-inflammatory drugs (NSAIDs) are frequently prescribed for chronic musculoskeletal pain, despite limited evidence of effectiveness and well-documented adverse effects. We assessed the effects of participating in a structured, personalized self-experiment ("N-of-1 trial") on analgesic prescribing in patients with chronic musculoskeletal pain. METHODS: We randomized 215 patients with chronic pain to participate in an N-of-1 trial facilitated by a mobile health app or to receive usual care. Medical records of participating patients were reviewed at enrollment and 6 months later to assess analgesic prescribing. We established thresholds of ≥ 50, ≥ 20, and > 0 morphine milligram equivalents (MMEs) per day to capture patients taking relatively high doses only, patients taking low-moderate as well as relatively high doses, and patients taking any dose of opioids, respectively. RESULTS: There was no significant difference between the N-of-1 and control groups in the percentage of patients prescribed any opioids (relative odds ratio (ROR) = 1.05; 95% confidence interval [CI] = 0.61 to 1.80, p = 0.87). There was a clinically substantial but statistically not significant reduction of the percentage of patients receiving ≥ 20 MME (ROR = 0.58; 95% CI = 0.33 to 1.04, p = 0.07) and also in the percentage receiving ≥ 50 MME (ROR = 0.50; 95% CI = 0.19 to 1.34, p = 0.17). There was a significant reduction in the proportion of patients in the N-of-1 group prescribed NSAIDs compared with control (relative odds ratio = 0.53; 95% CI = 0.29 to 0.96, p = 0.04), with no concomitant increase in average pain intensity. There was no significant change in use of adjunctive medications (acetaminophen, gabapentenoids, or topicals). DISCUSSION: These exploratory results suggest that participation in N-of-1 trials may reduce long-term use of NSAIDs; there is also a weak signal for an effect on use of opioids. Additional research is needed to confirm these results and elucidate possible mechanisms. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02116621.

Pharmacokinetic basis for dosing high-dose methotrexate in infants and young children with malignant brain tumours.

AIMS: No population pharmacokinetic studies of high-dose methotrexate (HDMTX) have been conducted in infants with brain tumours, which are a vulnerable population. The aim of this study was to evaluate HDMTX disposition in these children to provide a rational basis for MTX dosing. METHODS: Patients received 4 monthly courses of HDMTX (5 g/m2 or 2.5 g/m2 for infants aged ≤31 days) as a 24-h infusion. Serial samples were analysed for MTX by an enzyme immunoassay method. Pharmacokinetic parameters were estimated using nonlinear mixed effects population modelling. Demographics, concomitant medications and genetic polymorphisms were considered as pharmacokinetic covariates while MTX exposure and patient age were considered as covariates for Grade 3 and 4 toxicities. RESULTS: The population pharmacokinetics of HDMTX were estimated in 178 patients (age range 0.02-4.7 years) in 648 courses. The population clearance and volume were 90 mL/min/m2 and 14.4 L/m2 , respectively. Significant covariates on body surface area adjusted MTX clearance included estimated glomerular filtration rate and co-treatment with dexamethasone or vancomycin. No significant association was observed between MTX toxicity and MTX exposure, patient age, leucovorin dosage or duration. MTX clearance in infants ≤31 days at enrolment was 44% lower than in older infants, but their incidence of toxicity was not higher since they also received a lower MTX dosage. CONCLUSIONS: By aggressively following institutional clinical guidelines, HDMTX-related toxicities were low, and using covariates from the population pharmacokinetic model enabled the calculation of a rational dosage for this patient population for future clinical trials.

Bisphosphonate Use in Pediatric Oncology for Pain Management.

The use of bisphosphonates for pain control in children with cancer is not extensively studied. We retrospectively evaluated 35 children with cancer treated with intravenous bisphosphonates for pain management at a single institution from 1998 through 2015. We analyzed pain scores and opioid and adjuvant medication consumption before bisphosphonate administration, daily for 2 weeks, and at 3 and 4 weeks after administration. We also determined the time interval between diagnosis and first administration of bisphosphonates and duration of life after bisphosphonate administration. Mean pain scores were 2.45 (±2.96) and 0.75 (±1.69) before and 14 days after bisphosphonate administration, respectively ( P = .25), and morphine equivalent doses of opioids were 5.52 (±13.35) and 5.27 (±9.77), respectively ( P = .07). Opioid consumption was significantly decreased at days 4 to 8, days 11 to 12, and week 3 after first bisphosphonate administration. The median duration of life after first bisphosphonate administration was 80 days, indicating its use late in the course of treatment. Bisphosphonates did not significantly improve pain outcomes at 2 weeks, but opioid consumption was reduced at several time points during the first 3 weeks. The use of bisphosphonates earlier in the course of pediatric oncological disease should be evaluated in prospective investigations.

The Art of Analgesia: A Pilot Study of Art Museum Tours to Decrease Pain and Social Disconnection Among Individuals with Chronic Pain.

OBJECTIVE: This mixed-methods study examines the feasibility of art museum tours (Art Rx) as an intervention for individuals with chronic pain. METHODS: Art Rx provided 1-hour docent-led tours in an art museum to individuals with chronic pain. Survey data were collected pre-tour, immediately post-tour, and at three weeks post-tour. Pain intensity and unpleasantness were measured with a 0-10 numerical rating scale. Social disconnection was measured with a 12-item social disconnection scale. Participants also reported percent pain relief during the tour and program satisfaction in the post-tour survey. Change in pain and social disconnection was analyzed with paired t tests, bias-corrected and accelerated bootstrap confidence intervals (BCa CIs), and Cohen's d. Thematic analysis of semistructured interviews with participants explored the feasibility and perceived impact of the program. RESULTS: Fifty-four individuals participated in this study (mean age [SD] = 59 [14.5] years, 64.8% female), and 14 were interviewed. Fifty-seven percent of participants reported pain relief during the tour, with an average pain relief (SD) of 47% (34.61%). Participants reported decreased social disconnection and pain unpleasantness pre- to post-tour (3.65, BCa 95% CI = 1.70-5.73, P < 0.001, d = 0.37; and 0.49, BCa 95% CI = 0.06-0.90, P = 0.016, d = 0.20, respectively). Participants indicated high satisfaction with the program. Interviewees remarked on the isolating impact of chronic pain and how negative experiences with the health care system often compounded this sense of isolation. Participants experienced Art Rx as a positive and inclusive experience, with potential lasting benefit. CONCLUSIONS: Art museum tours for individuals with chronic pain are feasible, and participants reported positive effects on perceived social disconnection and pain.

Patient Perceptions of Their Own Data in mHealth Technology-Enabled N-of-1 Trials for Chronic Pain: Qualitative Study.

BACKGROUND: N-of-1 (individual comparison) trials are a promising approach for comparing the effectiveness of 2 or more treatments for individual patients; yet, few studies have qualitatively examined how patients use and make sense of their own patient-generated health data (PGHD) in the context of N-of-1 trials. OBJECTIVE: The objective of our study was to explore chronic pain patients' perceptions about the PGHD they compiled while comparing 2 chronic pain treatments and tracking their symptoms using a smartphone N-of-1 app in collaboration with their clinicians. METHODS: Semistructured interviews were recorded with 33 patients, a consecutive subset of the intervention group in a primary study testing the feasibility and effectiveness of the Trialist N-of-1 app. Interviews were transcribed verbatim, and a descriptive thematic analysis was completed. RESULTS: Patients were enthusiastic about recording and accessing their own data. They valued sharing data with clinicians but also used their data independently. CONCLUSIONS: N-of-1 trials remain a promising approach to evidence-based decision making. Patients appear to value their roles as trial participants but place as much or more importance on the independent use of trial data as on comparative effectiveness results. Future efforts to design patient-centered N-of-1 trials might consider adaptable designs that maximize patient flexibility and autonomy while preserving a collaborative role with clinicians and researchers.

Predictive models for identifying risk of readmission after index hospitalization for heart failure: A systematic review.

AIMS: Readmission rates for patients with heart failure have consistently remained high over the past two decades. As more electronic data, computing power, and newer statistical techniques become available, data-driven care could be achieved by creating predictive models for adverse outcomes such as readmissions. We therefore aimed to review models for predicting risk of readmission for patients admitted for heart failure. We also aimed to analyze and possibly group the predictors used across the models. METHODS: Major electronic databases were searched to identify studies that examined correlation between readmission for heart failure and risk factors using multivariate models. We rigorously followed the review process using PRISMA methodology and other established criteria for quality assessment of the studies. RESULTS: We did a detailed review of 334 papers and found 25 multivariate predictive models built using data from either health system or trials. A majority of models was built using multiple logistic regression followed by Cox proportional hazards regression. Some newer studies ventured into non-parametric and machine learning methods. Overall predictive accuracy with C-statistics ranged from 0.59 to 0.84. We examined significant predictors across the studies using clinical, administrative, and psychosocial groups. CONCLUSIONS: Complex disease management and correspondingly increasing costs for heart failure are driving innovations in building risk prediction models for readmission. Large volumes of diverse electronic data and new statistical methods have improved the predictive power of the models over the past two decades. More work is needed for calibration, external validation, and deployment of such models for clinical use.

Effect of Mobile Device-Supported Single-Patient Multi-crossover Trials on Treatment of Chronic Musculoskeletal Pain: A Randomized Clinical Trial.

Importance: Individually designed single-patient multi-crossover (n-of-1) trials can facilitate tailoring of treatments directed at various conditions, including chronic musculoskeletal pain (CMSP) but are potentially burdensome, which may limit uptake in research and practice. Objectives: To determine whether patients randomized to participate in an n-of-1 trial supported by a mobile health (mHealth) app would experience less pain and improved global health, adherence, satisfaction, and shared decision making compared with patients assigned to usual care. Design, Setting, and Participants: This randomized clinical trial compared participation in an individualized, mHealth-supported n-of-1 trial vs usual care. The participating 215 patients had CMSP for at least 6 weeks, had a smartphone or tablet with a data plan, were enrolled in northern California from July 2014 through July 2016, and were followed for up to 1 year by 48 clinicians in academic, community, Veterans Affairs, and military settings. Interventions: Intervention patients met with their clinicians and used a desktop interface to select treatments and trial parameters for an n-of-1 trial comparing 2 pain-management regimens. The mHealth app provided reminders to take designated treatments on assigned days and to upload responses to daily questions on pain and treatment-associated adverse effects. Control patients received care as usual. Main Outcomes and Measures: The primary outcome was change in the PROMIS (Patient-Reported Outcomes Measurement Information System) pain-related interference 8-item short-form scale (full scale range, 41-78) from baseline to 6 months. Secondary outcomes included patient-reported pain intensity, overall health, analgesic adherence, trust in clinician, satisfaction with care, medication-related shared decision making, and, for the n-of-1 group only, participant engagement and experience. Results: Among 215 patients (108 randomized to the n-of-1 intervention and 107 to control), 102 (47%) were women, and the mean (SD) age was 55.5 (11.1) years. At the 6-month follow-up, pain interference was reduced in both groups, though there was no difference between the intervention and control groups (-1.36 points; 95% CI, -2.91 to 0.19 points; P = .09). There were no advantages in secondary outcomes for intervention patients vs control patients except for higher medication-related shared decision making at 6 months (between-group difference, 11.9 points; 95% CI, 2.6-21.2 points; P = .01). Among patients assigned to the n-of-1 group, 88% (n = 86) affirmed that the mHealth app could help people like them manage their pain. Conclusions and Relevance: In this population of patients with CMSP, mHealth-supported n-of-1 trials were feasible and associated with a satisfactory user experience, but n-of-1 trial participation did not significantly improve pain interference at 6 months vs usual care. Trial Registration: ClinicalTrials.gov identifier: NCT02116621.