Negative mood is associated with sociobehavioral factors contributing to cardiovascular risk in an immigrant population.

BACKGROUND: After settling in the United States (US), immigrants often accumulate obesity and cardiovascular risk factors. As mood is often associated with health behaviors in the US population, mood may be an important mediating factor in immigrant populations. METHODS: The Healthy Immigrant Community (HIC) study, set in southeast Minnesota, enrolled 475 adult participants in a weight loss intervention designed to reduce cardiovascular risk. Baseline questionnaires assessed mood, nutrition, physical activity, self-efficacy for healthy eating and physical activity, social support, and cohesion. A single-item mood rating of poor or fair was considered "negative", while ratings of good, very good, or excellent were considered "positive". RESULTS: Hispanic/Latino (n = 268) and Somali (n = 181) adults enrolled in HIC completed baseline measures and were included in this analysis. Participants endorsing negative mood compared to positive mood had lower healthy eating scores (p = 0.02), lower physical activity levels (p = 0.03), lower confidence in eating a healthy diet (p = 0.001), and felt less of a sense of belonging to their community (p = 0.01). Those endorsing negative mood reported receiving less social support to eat healthy (p = < 0.001) and be physically active (p = 0.01). They also accessed community resources for healthy eating (p = 0.001) and physical activity (p = < 0.01) less frequently than participants endorsing positive mood. CONCLUSIONS: On self-report, negative mood was associated with less healthy nutrition, lower confidence in eating healthy, sedentary lifestyle, and perceived lack of belonging to the community. Integrating mood management and self-efficacy strategies may enhance the effectiveness of lifestyle interventions to reduce obesity and cardiovascular risk among immigrants who report negative mood. TRIAL REGISTRATION: ClinicalTrials.gov registration: NCT05136339; April 23, 2022.

Baseline Quality of Life is a Strong and Independent Prognostic Factor for Overall Survival in Metastatic Colorectal Cancer.

BACKGROUND: Previous studies have established that higher baseline quality of life (QOL) scores are associated with improved survival in patients with metastatic colorectal cancer (mCRC). We examined the relationship between overall survival (OS) and baseline QOL. PATIENTS AND METHODS: A total of 1 247 patients with mCRC participating in N9741 (comparing bolus 5-FU/LV, irinotecan [IFL] vs infusional 5-FU/leucovorin [LV]/oxaliplatin [FOLFOX] vs. irinotecan/oxaliplatin [IROX]) provided data at baseline on overall QOL using a single-item linear analogue self-assessment (LASA) 0-100 point scale. The association of OS according to clinically deficient (defined as CD-QOL, score 0-50) vs not clinically deficient (nCD-QOL, score 51-100) baseline QOL scores was tested. A multivariable analysis using Cox proportional hazards modeling was performed to adjust for the effects of multiple baseline factors. An exploratory analysis was performed evaluating OS according to baseline QOL status among patients who did or did not receive second-line therapy. RESULTS: Baseline QOL was a strong predictor of OS for the whole cohort (CD-QOL vs nCD-QOL: 11.2 months vs 18.4 months, P < .0001), and in each arm IFL 12.4 vs 15.1 months, FOLFOX 11.1 months vs 20.6 months, and IROX 8.9 months vs 18.1 months. Baseline QOL was associated with baseline performance status (PS) (P < .0001). After adjusting for PS and treatment arm, baseline QOL was still associated with OS (P = .017). CONCLUSIONS: Baseline QOL is an independent prognostic factor for OS in patients with mCRC. The demonstration that patient-assessed QOL and PS are independent prognostic indicators suggests that these assessments provide important complementary prognostic information.

An evaluation of the effect of lithium on taxane-induced neuropathy.

PURPOSE: No medications are known to protect against chemotherapy-induced peripheral neuropathy (CIPN). Pre-clinical models suggest that lithium may lessen taxane-induced neuropathy. Our aim was to use clinical data to assess whether concurrent lithium usage decreased the frequency or severity of CIPN in patients receiving taxane chemotherapy. METHODS: A retrospective analysis was performed using the electronic health record at Mayo Clinic to identify all patients prescribed concurrent lithium and paclitaxel. Four controls were matched to each case based on clinical variables. Neuropathy severity was graded from available patient and clinician reports. Rates of any neuropathy, dose reduction for CIPN, and treatment discontinuation for CIPN were compared. Conditional regression analysis was performed with propensity score matching. RESULTS: Six patients, receiving concurrent lithium and paclitaxel, were included in the analysis, and compared to 24 control cases. A similar number of paclitaxel cycles were administered to both groups. Any neuropathy was experienced by 33% (2/6) of patients receiving lithium and 38% (9/24) patients who did not receive lithium (p = 1.000). There was no difference in neuropathy severity (p = 0.8565), rate of chemotherapy dose reduction (17% vs. 17%, p = 1.000), or treatment discontinuation (17% vs 4%, p = 0.3655) for CIPN. In the propensity score analysis, the odds ratio for developing any neuropathy was 0.63 (95% confidence interval, 0.06 to 6.96, p = 0.7079). CONCLUSIONS: Lithium does not appear to significantly lessen the risk of neuropathy for patients receiving paclitaxel. IMPLICATIONS FOR CANCER SURVIVORS: Targeted approaches for preventing CIPN are desperately needed. Despite sound scientific rationale, the current study did not identify neuroprotective properties of lithium.

Identifying meaningful change on PROMIS short forms in cancer patients: a comparison of item response theory and classic test theory frameworks.

BACKGROUND: This study compares classical test theory and item response theory frameworks to determine reliable change. Reliable change followed by anchoring to the change in categorically distinct responses on a criterion measure is a useful method to detect meaningful change on a target measure. METHODS: Adult cancer patients were recruited from five cancer centers. Baseline and follow-up assessments at 6 weeks were administered. We investigated short forms derived from PROMIS® item banks on anxiety, depression, fatigue, pain intensity, pain interference, and sleep disturbance. We detected reliable change using reliable change index (RCI). We derived the T-scores corresponding to the RCI calculated under IRT and CTT frameworks using PROMIS® short forms. For changes that were reliable, meaningful change was identified using patient-reported change in PRO-CTCAE by at least one level. For both CTT and IRT approaches, we applied one-sided tests to detect reliable improvement or worsening using RCI. We compared the percentages of patients with reliable change and reliable/meaningful change. RESULTS: The amount of change in T score corresponding to RCICTT of 1.65 ranged from 5.1 to 9.2 depending on domains. The amount of change corresponding to RCIIRT of 1.65 varied across the score range, and the minimum change ranged from 3.0 to 8.2 depending on domains. Across domains, the RCICTT and RCIIRT classified 80% to 98% of the patients consistently. When there was disagreement, the RCIIRT tended to identify more patients as having reliably changed compared to RCICTT if scores at both timepoints were in the range of 43 to 78 in anxiety, 45 to 70 in depression, 38 to 80 in fatigue, 35 to 78 in sleep disturbance, and 48 to 74 in pain interference, due to smaller standard errors in these ranges using the IRT method. The CTT method found more changes compared to IRT for the pain intensity domain that was shorter in length. Using RCICTT, 22% to 66% had reliable change in either direction depending on domains, and among these patients, 62% to 83% had meaningful change. Using RCIIRT, 37% to 68% had reliable change in either direction, and among these patients, 62% to 81% had meaningful change. CONCLUSION: Applying the two-step criteria demonstrated in this study, we determined how much change is needed to declare reliable change at different levels of baseline scores. We offer reference values for percentage of patients who meaningfully change for investigators using the PROMIS instruments in oncology.

Decision aids for localized prostate cancer in diverse minority men: Primary outcome results from a multicenter cancer care delivery trial (Alliance A191402CD).

BACKGROUND: Decision aids (DAs) can improve knowledge for prostate cancer treatment. However, the relative effects of DAs delivered within the clinical encounter and in more diverse patient populations are unknown. A multicenter cluster randomized controlled trial with a 2×2 factorial design was performed to test the effectiveness of within-visit and previsit DAs for localized prostate cancer, and minority men were oversampled. METHODS: The interventions were delivered in urology practices affiliated with the NCI Community Oncology Research Program Alliance Research Base. The primary outcome was prostate cancer knowledge (percent correct on a 12-item measure) assessed immediately after a urology consultation. RESULTS: Four sites administered the previsit DA (39 patients), 4 sites administered the within-visit DA (44 patients), 3 sites administered both previsit and within-visit DAs (25 patients), and 4 sites provided usual care (50 patients). The median percent correct in prostate cancer knowledge, based on the postvisit knowledge assessment after the intervention delivery, was as follows: 75% for the pre+within-visit DA study arm, 67% for the previsit DA only arm, 58% for the within-visit DA only arm, and 58% for the usual-care arm. Neither the previsit DA nor the within-visit DA had a significant impact on patient knowledge of prostate cancer treatments at the prespecified 2.5% significance level (P = .132 and P = .977, respectively). CONCLUSIONS: DAs for localized prostate cancer treatment provided at 2 different points in the care continuum in a trial that oversampled minority men did not confer measurable gains in prostate cancer knowledge.

Effects of patient-reported outcome assessment order.

BACKGROUND: In clinical trials and clinical practice, patient-reported outcomes are almost always assessed using multiple patient-reported outcome measures at the same time. This raises concerns about whether patient responses are affected by the order in which the patient-reported outcome measures are administered. METHODS: This questionnaire-based study of order effects included adult cancer patients from five cancer centers. Patients were randomly assigned to complete questionnaires via paper booklets, interactive voice response system, or tablet web survey. Linear Analogue Self-Assessment, Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events, and Patient-Reported Outcomes Measurement Information System assessment tools were each used to measure general health, physical function, social function, emotional distress/anxiety, emotional distress/depression, fatigue, sleep, and pain. The order in which the three tools, and domains within tools, were presented to patients was randomized. Rates of missing data, scale scores, and Cronbach's alpha coefficients were compared by the order in which they were assessed. Analyses included Cochran-Armitage trend tests and mixed models adjusted for performance score, age, sex, cancer type, and curative intent. RESULTS: A total of 1830 patients provided baseline patient-reported outcome assessments. There were no significant trends in rates of missing values by whether a scale was assessed earlier or later. The largest order effect for scale scores was due to a large mean score at one assessment time point. The largest difference in Cronbach's alpha between the versions for the Patient-Reported Outcomes Measurement Information System scales was 0.106. CONCLUSION: The well-being of a cancer patient has many different aspects such as pain, fatigue, depression, and anxiety. These are assessed using a variety of surveys often collected at the same time. This study shows that the order in which the different aspects are collected from the patient is not important.

Choosing and Using Patient-Reported Outcome Measures in Clinical Practice.

The increasing use of patient-reported outcome (PRO) measures is forcing clinicians and health care systems to decide which to select and how to incorporate them into their records and clinical workflows. This overview addresses 3 topics related to these concerns. First, a literature review summarizes key psychometric and practical factors (such as reliability, responsiveness, computer adaptive testing, and interpretability) in choosing PROs for clinical practice. Second, 3 clinical decision support issues are highlighted: gathering PROs, electronic health record effect on providers, and incorporating PROs into clinical decision support design and implementation. Lastly, the salience of crosscutting domains as well as 9 key pragmatic decisions are reviewed. Crosscutting domains are those that are relevant across most medical and mental health conditions, such as the SPADE symptom pentad (sleep problems, pain, anxiety, depression, low energy/fatigue) and physical functioning. The 9 pragmatic decisions include (1) generic vs disease-specific scales; (2) single- vs multidomain scales; (3) universal scales vs user-choice selection; (4) number of domains to measure; (5) prioritization of domains when multiple domains are assessed; (6) action thresholds; (7) clinical purpose (screening vs monitoring); as well as the (8) frequency and (9) logistical aspects of PRO administration.

Expanding Beyond Maximum Grade: Chemotherapy Toxicity over Time by Age and Performance Status in Advanced Non-Small Cell Lung Cancer in CALGB 9730 (Alliance A151729).

BACKGROUND: Prior comparisons of chemotherapy adverse events (AEs) by age and performance status (PS) are limited by the traditional maximum grade approach, which ignores low-grade AEs and longitudinal changes. MATERIALS AND METHODS: To compare fatigue and neuropathy longitudinally by age (<65, ≥65 years) and PS (0-1, 2), we analyzed data from a large phase III trial of carboplatin and paclitaxel versus paclitaxel for advanced non-small cell lung cancer (CALGB 9730, n = 529). We performed multivariable (a) linear mixed models to estimate mean AE grade over time, (b) linear regression to estimate area under the curve (AUC), and (c) proportional hazards models to estimate the hazard ratio of developing grade ≥2 AE, as well as traditional maximum grade analyses. RESULTS: Older patients had on average a 0.17-point (95% confidence interval [CI], 0.00-0.34; p = .049) higher mean fatigue grade longitudinally compared with younger patients. PS 2 was associated with earlier development of grade ≥2 fatigue (hazard ratio [HR], 1.56; 95% CI, 1.07-2.27; p = .02). For neuropathy, older age was associated with earlier development of grade ≥2 neuropathy (HR, 1.41; 95% CI, 1.00-1.97; p = .049). Patients with PS 2 had a 1.30 point lower neuropathy AUC (95% CI, -2.36 to -0.25; p = .02) compared with PS 0-1. In contrast, maximum grade analyses only detected a higher percentage of older adults with grade ≥3 fatigue and neuropathy at some point during treatment. CONCLUSION: Our comparison of complementary but distinct aspects of chemotherapy toxicity identified important longitudinal differences in fatigue and neuropathy by age and PS that are missed by the traditional maximum grade approach. Clinical trial identification number: NCT00003117 (CALGB 9730) IMPLICATIONS FOR PRACTICE: The traditional maximum grade approach ignores persistent low-grade adverse events (AEs) and changes over time. This toxicity over time analysis of fatigue and neuropathy during chemotherapy for advanced non-small cell lung cancer demonstrates how to use longitudinal methods to comprehensively characterize AEs over time by age and performance status (PS). We identified important longitudinal differences in fatigue and neuropathy that are missed by the maximum grade approach. This new information about how older adults and patients with PS 2 experience these toxicities longitudinally may be used clinically to improve discussions about treatment options and what to expect to inform shared decision making and symptom management.

Prospective longitudinal cohort study of patient recovery after major gastrointestinal surgery: is there a difference between minimally invasive and open approaches?

BACKGROUND: Surgeons use the absence of post-operative complications to define recovery while patients define recovery as return to normal function. We aimed to better define the recovery process after minimally invasive surgery (MIS) and open gastrointestinal surgery. METHODS: Patients scheduled for open or MIS pancreaticoduodenectomy, esophagectomy, colectomy, and proctectomy were prospectively enrolled. Patient-reported outcomes (PROs) were collected using validated PROMIS and LASA scales pre-operatively, on post-operative days 2, 7, 14, 30, and monthly until 6 months. Patients were also asked if they felt fully recovered. Descriptive statistics and area under the curve (AUC) were used to compare approaches. Multivariable mixed-effects repeated measures models and logistic regression were used to control for covariates. RESULTS: 340 patients met inclusion criteria (158 open and 182 MIS). Median age was 60 years with 44% women. The PRO showed improved post-operative QOL scores in MIS compared to open on all measures by AUC. None of these difference persisted at 6-months. After adjusting for covariates, MIS had higher overall QOL scores at day 14 (Estimate + 0.58, p = 0.02) and 30 (+ 0.56, p = 0.03). Differences did not persist at 3 and 6 months (both p > 0.05). At 1, 3, and 6 months, 20%, 47%, and 61% of patients reported feeling completely recovered. On adjusted analysis there was no difference in odds of complete recovery in MIS at 1 (OR 1.07 [95% CI 0.53-2.14] and 3 months (1.12 [0.63-2.01]) compared to open. MIS patients were more likely to report complete recovery at 6 months (1.87 [1.05-3.33]). CONCLUSION: MIS patients reported improved PRO on selected QOL measures early in the recovery period compared to open. There was no difference in long-term QOL data between MIS and open patients. Two-thirds (61%) of patients reported being fully recovered at 6 months with MIS patients being more likely to report a complete recovery.

Social networks and obesity among Somali immigrants and refugees.

BACKGROUND: Somali immigrants and refugees to the United States are at high risk for obesity and related cardiovascular risk. Social network factors influence health behaviors and are important contributors to the obesity epidemic. The objective of this study was to describe social networks and obesity-related characteristics among adult Somali immigrants in a Minnesota city in order to inform a community-based, participatory, research-derived, social network intervention to decrease obesity rates. METHODS: Survey data (demographics, general health measures, and sociobehavioral and network measures) and height and weight measures (for calculating body mass index) were collected from adult Somali immigrants by bilingual study team members at community locations. Descriptive statistics were used to report the survey and biometric data. Logistic regression models were used to describe the basic associations of participants and network factors. Network data were analyzed to identify nodes and ties, to visualize the network, and to identify potential interventionists for a future social network intervention. RESULTS: Of the 646 participants, 50% were overweight or affected by obesity. The network had 1703 nodes with 3583 ties between nodes, and modularity was high (0.75). Compared with respondents of normal weight, participants who were overweight or affected by obesity had more network members who were also overweight or obese (odds ratio [OR], 2.90; 95% CI, 1.11-7.56; P = .03); this was most notable for men (OR, 4.58; 95% CI, 1.22-17.22; P = .02) and suggestive for those 50 years or older (OR, 24.23; 95% CI, 1.55-377.83; P = .03). Weight loss intention among participants who were overweight or affected by obesity was associated with number of family members and friends trying to lose weight, enabling functional network factors (social norms for weight loss, social support for healthy eating, and social cohesion), and less favorable obesogenic social norms. CONCLUSIONS: In this community sample of Somali immigrants, distinct social networks are clustered by weight status, and social contacts and functional network characteristics are related to individuals' weight loss intentions. These factors should be considered in weight loss interventions and programs. A social network intervention targeting weight loss, within a community-based participatory research framework, is feasible in this vulnerable population.

Association of social network factors with weight status and weight loss intentions among hispanic adults.

Hispanic adults have the highest obesity prevalence in the United States, but little is known about weight-related social network influences. A community-based sample of 610 Hispanic participants completed height/weight and a survey. The proportion of overweight or obese (OW/OB) network members was higher for OW/OB respondents compared to normal weight respondents. Participants with high weight loss intentions reported more positive social norms for weight control, social support, and social cohesion. If most or all of OW/OB participant's social contacts were trying to lose weight, the odds that they were likely to try to lose weight was four times higher than other participants. The relationship between weight loss intentions and number of social contacts trying to lose weight was strongly mediated by social norms for weight control and social support. These results suggest that social contacts and functional network characteristics may impact weight status and weight control intentions among Hispanic adults.

Club Fit: Development of a Physical Activity and Healthy Eating Intervention at a Boys & Girls Club After School Program.

Children and adolescents from minority and low income backgrounds face social and environmental challenges to engaging in physical activity and healthy eating to maintain a healthy weight. In this study, we present pilot work to develop and implement a multi-component physical activity and healthy eating intervention at a Boys & Girls Club (BGC) afterschool program. Using a community-based participatory approach, BGC staff and academic researchers developed intervention components informed by formative studies and based on a Social Ecological Theory framework. Components included healthy eating and physical activity policy implementation, staff training, a challenge and self-monitoring program for healthy behaviors, a peer-coaching program for healthy behaviors, and a social marketing campaign. We assessed pilot feasibility through a single group, pre-post study design with measures collected at baseline and 6 months. The sample included 61 children with a mean age of 10.4 years. Mean (SD) body mass index (BMI) percentile was 72.8 (28.9); 47.5% were in the healthy weight range for their age. We found statistically significant improvements of self-efficacy and motivation for physical activity. Self-efficacy and motivation for fruit and vegetable consumption, sugary beverage consumption, and screen time improved but were not statistically different from baseline. We found no improvements of perceived social support, objectively measured physical activity, or self-reported dietary quality. Though BMI did not improve overall, a dose effect was observed such that attendance in Club Fit specific programming was significantly correlated with decreased BMI z scores. Processes and products from this study may be helpful to other communities aiming to address childhood obesity prevention through afterschool programs.

Effect of Doxepin Mouthwash or Diphenhydramine-Lidocaine-Antacid Mouthwash vs Placebo on Radiotherapy-Related Oral Mucositis Pain: The Alliance A221304 Randomized Clinical Trial.

Importance: Oral mucositis causes substantial morbidity during head and neck radiotherapy. In a randomized study, doxepin mouthwash was shown to reduce oral mucositis-related pain. A common mouthwash comprising diphenhydramine-lidocaine-antacid is also widely used. Objective: To evaluate the effect of doxepin mouthwash or diphenhydramine-lidocaine-antacid mouthwash for the treatment of oral mucositis-related pain. Design, Setting, and Participants: A phase 3 randomized trial was conducted from November 1, 2014, to May 16, 2016, at 30 US institutions and included 275 patients who underwent definitive head and neck radiotherapy, had an oral mucositis pain score of 4 points or greater (scale, 0-10), and were followed up for a maximum of 28 days. Interventions: Ninety-two patients were randomized to doxepin mouthwash (25 mg/5 mL water); 91 patients to diphenhydramine-lidocaine-antacid; and 92 patients to placebo. Main Outcome and Measures: The primary end point was total oral mucositis pain reduction (defined by the area under the curve and adjusted for baseline pain score) during the 4 hours after a single dose of doxepin mouthwash or diphenhydramine-lidocaine-antacid mouthwash compared with a single dose of placebo. The minimal clinically important difference was a 3.5-point change. The secondary end points included drowsiness, unpleasant taste, and stinging or burning. All scales ranged from 0 (best) to 10 (worst). Results: Among the 275 patients randomized (median age, 61 years; 58 [21%] women), 227 (83%) completed treatment per protocol. Mucositis pain during the first 4 hours decreased by 11.6 points in the doxepin mouthwash group, by 11.7 points in the diphenhydramine-lidocaine-antacid mouthwash group, and by 8.7 points in the placebo group. The between-group difference was 2.9 points (95% CI, 0.2-6.0; P = .02) for doxepin mouthwash vs placebo and 3.0 points (95% CI, 0.1-5.9; P = .004) for diphenhydramine-lidocaine-antacid mouthwash vs placebo. More drowsiness was reported with doxepin mouthwash vs placebo (by 1.5 points [95% CI, 0-4.0]; P = .03), unpleasant taste (by 1.5 points [95% CI, 0-3.0]; P = .002), and stinging or burning (by 4.0 points [95% CI, 2.5-5.0]; P < .001). Maximum grade 3 adverse events for the doxepin mouthwash occurred in 3 patients (4%); diphenhydramine-lidocaine-antacid mouthwash, 3 (4%); and placebo, 2 (2%). Fatigue was reported by 5 patients (6%) in the doxepin mouthwash group and no patients in the diphenhydramine-lidocaine-antacid mouthwash group. Conclusions and Relevance: Among patients undergoing head and neck radiotherapy, the use of doxepin mouthwash or diphenhydramine-lidocaine-antacid mouthwash vs placebo significantly reduced oral mucositis pain during the first 4 hours after administration; however, the effect size was less than the minimal clinically important difference. Further research is needed to assess longer-term efficacy and safety for both mouthwashes. Trial Registration: ClinicalTrials.gov Identifier: NCT02229539.

Long-Term Return to Functional Baseline After Mechanical Ventilation in the ICU.

OBJECTIVE: Predictors of long-term functional impairment in acute respiratory failure of all causes are poorly understood. Our objective was to assess the frequency and predictors of long-term functional impairment or death after invasive mechanical ventilation for acute respiratory failure of all causes. DESIGN: Population-based, observational cohort study. SETTING: Eight adult ICUs of a single center. PATIENTS: All adult patients from Olmsted County, Minnesota, without baseline functional impairment who received mechanical ventilation in ICUs for acute respiratory failure of all causes from 2005 through 2009. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: In total, 743 patients without baseline functional impairment received mechanical ventilation in the ICU. At 1- and 5-year follow-up, the rates of survival with return to baseline functional ability were 61% (366/597) and 53% (356/669). Among 71 patients with new functional impairment at 1 year, 55% (39/71) had recovered and were alive without functional impairment at 5 years. Factors predictive of new functional impairment or death at 1 year were age, comorbidities, discharge to other than home, mechanical ventilation of 7 days or longer, and stroke. Of factors known at the time of intubation, the following are predictive of new functional impairment or death: age, comorbidities, nonsurgical condition, Acute Physiology and Chronic Health Evaluation III score, stroke, and sepsis. Post hoc sensitivity analyses revealed no significant change in predictor variables in patient populations when stroke was excluded or who received more than 48 hours of mechanical ventilation. CONCLUSIONS: At 1- and 5-year follow-up, many patients who received mechanical ventilation for acute respiratory failure from all causes are no longer alive or have new moderate-to-severe functional impairment. Functional recovery between year 1 and year 5 is possible and common. Sepsis, stroke, illness severity, age, and comorbidities predict long-term functional outcome at intubation.

Multicenter derivation and validation of an early warning score for acute respiratory failure or death in the hospital.

BACKGROUND: Acute respiratory failure occurs frequently in hospitalized patients and often starts before ICU admission. A risk stratification tool to predict mortality and risk for mechanical ventilation (MV) may allow for earlier evaluation and intervention. We developed and validated an automated electronic health record (EHR)-based model-Accurate Prediction of Prolonged Ventilation (APPROVE)-to identify patients at risk of death or respiratory failure requiring >= 48 h of MV. METHODS: This was an observational study of adults admitted to four hospitals in 2013 or a fifth hospital in 2017. Clinical data were extracted from the EHRs. The 2013 patients were randomly split 50:50 into a derivation/validation cohort. The qualifying event was death or intubation leading to MV >= 48 h. Random forest method was used in model derivation. APPROVE was calculated retrospectively whenever data were available in 2013, and prospectively every 4 h after hospital admission in 2017. The Modified Early Warning Score (MEWS) and National Early Warning Score (NEWS) were calculated at the same times as APPROVE. Clinicians were not alerted except for APPROVE in 2017cohort. RESULTS: There were 68,775 admissions in 2013 and 2258 in 2017. APPROVE had an area under the receiver operator curve of 0.87 (95% CI 0.85-0.88) in 2013 and 0.90 (95% CI 0.84-0.95) in 2017, which is significantly better than the MEWS and NEWS in 2013 but similar to the MEWS and NEWS in 2017. At a threshold of > 0.25, APPROVE had similar sensitivity and positive predictive value (PPV) (sensitivity 63% and PPV 21% in 2013 vs 64% and 16%, respectively, in 2017). Compared to APPROVE in 2013, at a threshold to achieve comparable PPV (19% at MEWS > 4 and 22% at NEWS > 6), the MEWS and NEWS had lower sensitivity (16% for MEWS and NEWS). Similarly in 2017, at a comparable sensitivity threshold (64% for APPROVE > 0.25 and 67% for MEWS and NEWS > 4), more patients who triggered an alert developed the event with APPROVE (PPV 16%) while achieving a lower false positive rate (FPR 5%) compared to the MEWS (PPV 7%, FPR 14%) and NEWS (PPV 4%, FPR 25%). CONCLUSIONS: An automated EHR model to identify patients at high risk of MV or death was validated retrospectively and prospectively, and was determined to be feasible for real-time risk identification. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02488174 . Registered on 18 March 2015.

Consequences of the 48-h rule: A lens into the psychiatric patient flow through an emergency department.

OBJECTIVE: Psychiatric patient boarding in emergency department (ED) is a severe and growing problem. In July 2013, Minnesota implemented a law requiring jailed persons committed to state psychiatric facilities be transferred within 48-h of commitment. This study aims to quantify the effect of this law on a large ED's psychiatric patient flow. METHODS: A pre- and post- comparison of 2011-2015 ED length of stay (LOS) for adult psychiatric patients was performed using electronic medical record data. Comparisons of the median LOS were assessed using a segmented regression model with time series error, and risk differences (RD) were used to determine changes in the proportion of patients with LOS ≥3 and ≥5days. Changes in patient disposition proportions were assessed using risk ratios. RESULTS: The median ED LOS for patients admitted for psychiatric care increased by 5.22h from 2011 to 2015 (95% CI: (4.33, 7.15)), while the frequency of patient encounters remained constant. Although no significant difference in the rate of ED LOS increase was found pre- and post- implementation, the proportion of adults with LOS ≥3days and ≥15days increased (RD 0.017 (95% CI: (0.013, 0.021)); 0.002 (95% CI: (0.001,0.004)), respectively). CONCLUSIONS: The proportion of ED adult psychiatric patients experiencing prolonged LOS increased following the implementation of a statewide law requiring patients committed through the criminal justice system be transferred to a state psychiatric hospital within 48h. Identifying characteristics of subsets of psychiatric patients disproportionally affected could suggest focused healthcare system improvements to improve ED psychiatric care.

Health Coaching and Chronic Obstructive Pulmonary Disease Rehospitalization. A Randomized Study.

RATIONALE: Hospital readmission for chronic obstructive pulmonary disease (COPD) has attracted attention owing to the burden to patients and the health care system. There is a knowledge gap on approaches to reducing COPD readmissions. OBJECTIVES: To determine the effect of comprehensive health coaching on the rate of COPD readmissions. METHODS: A total of 215 patients hospitalized for a COPD exacerbation were randomized at hospital discharge to receive either (1) motivational interviewing-based health coaching plus a written action plan for exacerbations (the use of antibiotics and oral steroids) and brief exercise advice or (2) usual care. MEASUREMENTS AND MAIN RESULTS: We evaluated the rate of COPD-related hospitalizations during 1 year of follow-up. The absolute risk reductions of COPD-related rehospitalization in the health coaching group were 7.5% (P = 0.01), 11.0% (P = 0.02), 11.6% (P = 0.03), 11.4% (P = 0.05), and 5.4% (P = 0.24) at 1, 3, 6, 9, and 12 months, respectively, compared with the control group. The odds ratios for COPD hospitalization in the intervention arm compared with the control arm were 0.09 (95% confidence interval [CI], 0.01-0.77) at 1 month postdischarge, 0.37 (95% CI, 0.15-0.91) at 3 months postdischarge, 0.43 (95% CI, 0.20-0.94) at 6 months postdischarge, and 0.60 (95% CI, 0.30-1.20) at 1 year postdischarge. The missing value rate for the primary outcome was 0.4% (one patient). Disease-specific quality of life improved significantly in the health coaching group compared with the control group at 6 and 12 months, based on the Chronic Respiratory Disease Questionnaire emotional score (emotion and mastery domains) and physical score (dyspnea and fatigue domains) (P < 0.05). There were no differences between groups in measured physical activity at any time point. CONCLUSIONS: Health coaching may represent a feasible and possibly effective intervention designed to reduce COPD readmissions. Clinical trial registered with www.clinicaltrials.gov (NCT01058486).

Effect of Longer-Interval vs Standard Dosing of Zoledronic Acid on Skeletal Events in Patients With Bone Metastases: A Randomized Clinical Trial.

Importance: Zoledronic acid, a third-generation aminobisphosphonate, reduces the incidence of skeletal-related events and pain in patients with bone metastases. The optimal dosing interval for zoledronic acid is uncertain. Objective: To determine whether zoledronic acid administered every 12 weeks is noninferior to zoledronic acid administered every 4 weeks. Design, Setting, Participants: Randomized, open-label clinical trial conducted at 269 academic and community sites in the United States. Patients (n = 1822) with metastatic breast cancer, metastatic prostate cancer, or multiple myeloma who had at least 1 site of bone involvement were enrolled between May 2009 and April 2012; follow-up concluded in April 2014. Interventions: Patients were randomized to receive zoledronic acid administered intravenously every 4 weeks (n = 911) vs every 12 weeks (n = 911) for 2 years. Main Outcomes and Measures: The primary end point was the proportion of patients having at least 1 skeletal-related event (defined as clinical fracture, spinal cord compression, radiation to bone, or surgery involving bone) within 2 years after randomization and a between-group absolute difference of 7% as the noninferiority margin. Secondary end points included the proportion of patients with at least 1 skeletal-related event by disease type, pain as assessed by the Brief Pain Inventory (range, 0-10; higher scores indicate worse pain), Eastern Cooperative Oncology Group performance status (range, 0-4; higher scores indicate worse disability), incidence of osteonecrosis of the jaw, kidney dysfunction, skeletal morbidity rate (mean number of skeletal-related events per year), and, in a subset of 553 patients, suppression of bone turnover (assessed by C-terminal telopeptide levels). Results: Among 1822 patients who were randomized (median age, 65 years; 980 [53.8%] women; 855 with breast cancer, 689 with prostate cancer, and 278 with multiple myeloma), 795 completed the study at 2 years. A total of 260 patients (29.5%) in the zoledronic acid every 4-week dosing group and 253 patients (28.6%) in the every 12-week dosing group experienced at least 1 skeletal-related event within 2 years of randomization (risk difference of -0.3% [1-sided 95% CI, -4% to ∞]; P < .001 for noninferiority). The proportions of skeletal-related events did not differ significantly between the every 4-week dosing group vs the every 12-week dosing group for patients with breast cancer, prostate cancer, or multiple myeloma. Pain scores, performance status scores, incidence of jaw osteonecrosis, and kidney dysfunction did not differ significantly between the treatment groups. Skeletal morbidity rates were numerically identical in both groups, but bone turnover was greater (C-terminal telopeptide levels were higher) among patients who received zoledronic acid every 12 weeks. Conclusions and Relevance: Among patients with bone metastases due to breast cancer, prostate cancer, or multiple myeloma, the use of zoledronic acid every 12 weeks compared with the standard dosing interval of every 4 weeks did not result in an increased risk of skeletal events over 2 years. This longer interval may be an acceptable treatment option. Trial Registration: clinicaltrials.gov Identifier: NCT00869206.

Longitudinal adverse event assessment in oncology clinical trials: the Toxicity over Time (ToxT) analysis of Alliance trials NCCTG N9741 and 979254.

BACKGROUND: Traditional methods of reporting adverse events in clinical trials are inadequate for modern cancer treatments with chronic administration. Conventional analysis and display of maximum grade adverse events do not capture toxicity profiles that evolve over time or longer lasting, lower grade toxic effects; we aimed to address this shortcoming in this study. METHODS: We developed an analytic approach and standardised, comprehensive format, the Toxicity over Time (ToxT) approach, which combines graphs and adverse event tabular displays with multiple longitudinal statistical techniques into a readily applicable method to study toxic effects. Plots visualising summary statistics or individual patient data over discrete timepoints were combined with statistical methods including the following longitudinal techniques: repeated measures models that describe the changes in adverse events across all cycles of treatment; time-to-event analyses of first and worst grade toxicity; and area under the curve (AUC) analyses summarising adverse event profiles over the entire course of a study, including chronic low-grade events. We applied ToxT analysis to adverse event data from two completed North Central Cancer Treatment Group (NCCTG/Alliance) trials: N9741 (NCT00003594), in which different combinations of oxaliplatin, 5-fluorouracil, and irinotecan were investigated for metastatic colorectal cancer, and 979254, in which survivors of breast cancer were given venlafaxine or placebo for control of hot flashes. FINDINGS: In trial NCCTG 979254 there was a higher incidence of late-occurring dry mouth in patients who were given venlafaxine than in those given placebo (week 1 [baseline]: 13% [six incidence in 48 patients, SD 5] vs 22% [11/49, SD 6]; p=0·20; week 5: 49% [24/49, 7] vs 2% [1/46, 2]; p<0·0001). In trial NCCTG N9741 there was an increased incidence of early nausea for patients given irinotecan plus oxaliplatin (IROX) compared with those given 5-fluorouracil plus oxaliplatin (FOLFOX; cycle 1 mean grade nausea 1·1 [SD 1·0] vs 0·6 [0·7]; p<0·0001). Event charts showed earlier occurrences of higher grades of diarrhoea for patients given IROX compared with those given FOLFOX, and the AUC analysis shows a higher magnitude of diarrhoea consistently over time throughout the study in patients given IROX versus those given FOLFOX (mean AUC 4·2 [SD 5·2] vs 2·9 [4·2]; p<0·0001). INTERPRETATION: The ToxT analytical approach incorporates the dimension of time into adverse event assessment and offers a more comprehensive depiction of toxic effects than present methods. With new, continuously administered targeted agents, immunotherapy, and maintenance regimens, these improved longitudinal analyses are directly relevant to patients and are crucial in cancer clinical trials. FUNDING: National Cancer Institute of the National Institutes of Health and the Mayo Comprehensive Cancer Center.

Impact of self-reported physical activity and health promotion behaviors on lung cancer survivorship.

BACKGROUND: There is some initial evidence that an enhanced physical activity level can improve fquality of life, and possibly survival among patients with lung cancer. The primary aim of this project was to evaluate the impact of physical activity on the quality and quantity of life of lung cancer survivors. METHODS: Between January 1, 1997, and December 31, 2009, a total of 1466 lung cancer survivors completed a questionnaire with patient-reported outcomes for quality of life (QOL), demographics, disease and clinical characteristics, and a measure of physical activity (Baecke Questionnaire). Chi-square tests compared lung cancer survivors who reported being physically active versus not on a variety of the other covariates. Kaplan-Meier estimates and Cox models evaluated the prognostic importance of physical activity level on Overall Survival (OS). RESULTS: Roughly half of the lung cancer survivors had advanced stage disease at the time of survey. Treatment prevalence rates were 61, 54, and 33 % for surgery, chemotherapy and radiotherapy, respectively. The majority (77 %) of survivors reported themselves as physically active. Physically active survivors reported greater activity across all individual Baecke items. Lung cancer survivor-reported QOL indicated the benefits of physical activity in all domains. Survivors receiving chemotherapy or radiation at the time of questionnaire completion were less likely to be physically active (74 and 73 % respectively). In contrast, 84 % of surgical patients were physically active. Disease recurrence rates were the same for physically active and inactive patients (81 % vs 82 %, p = 0.62). Physically active patients survived an average of 4 more years than those who were not physically active (8.4 years versus 4.4 years respectively, log rank p < 0.0001). CONCLUSIONS: Being physically active was related to profound advantages in QOL and survival in a large sample of lung cancer survivors.