Setting International Standards in Analyzing Patient-Reported Outcomes and Quality of Life Endpoints in Cancer Clinical Trials-Innovative Medicines Initiative (SISAQOL-IMI): stakeholder views, objectives, and procedures.

Patient-reported outcomes (PROs), such as symptoms, functioning, and other health-related quality-of-life concepts are gaining a more prominent role in the benefit-risk assessment of cancer therapies. However, varying ways of analysing, presenting, and interpreting PRO data could lead to erroneous and inconsistent decisions on the part of stakeholders, adversely affecting patient care and outcomes. The Setting International Standards in Analyzing Patient-Reported Outcomes and Quality of Life Endpoints in Cancer Clinical Trials-Innovative Medicines Initiative (SISAQOL-IMI) Consortium builds on the existing SISAQOL work to establish recommendations on design, analysis, presentation, and interpretation for PRO data in cancer clinical trials, with an expanded set of topics, including more in-depth recommendations for randomised controlled trials and single-arm studies, and for defining clinically meaningful change. This Policy Review presents international stakeholder views on the need for SISAQOL-IMI, the agreed on and prioritised set of PRO objectives, and a roadmap to ensure that international consensus recommendations are achieved.

Pexidartinib Provides Modest Pain Relief in Patients With Tenosynovial Giant Cell Tumor: Results From ENLIVEN.

BACKGROUND: The double-blind, randomized, placebo-controlled phase 3 study of orally administered PLX3397 in patients with pigmented villonodular synovitis or giant cell tumor of the tendon sheath (ENLIVEN) showed that pexidartinib provides a robust objective tumor response in adults with tenosynovial giant cell tumors (TGCT) not amenable to improvement with surgery. Based on these results, in 2019, pexidartinib received accelerated approval in the United States in this population as a breakthrough therapy under an orphan drug designation. However, the ability of pexidartinib to relieve pain in ENLIVEN was not fully detailed, and the relationship between pain relief and objective tumor response was not described. QUESTIONS/PURPOSES: (1) What level of pain relief was achieved by pexidartinib treatment in ENLIVEN? (2) How was pain relief related to objective tumor responses? (3) How durable was pain relief? METHODS: The current study included planned primary and exploratory assessments of patient-assessed worst pain at the site of the tumor in the ENLIVEN trial. ENLIVEN was a phase 3 randomized, placebo-controlled clinical trial in which adults with TGCT not amenable to improvement with surgery received pexidartinib or placebo for 24 weeks, after which eligible patients could receive open-label pexidartinib. Of 174 patients assessed for eligibility, 121 were randomized (50% [60] to placebo, 50% [61] to pexidartinib), and 120 were given either placebo or pexidartinib (59 received placebo and 61 received pexidartinib) and were included in an intent-to-treat analysis. Fifty-nine percent (71 of 120) of the overall treated population was female, and 88% (106 of 120) were White. Mean age was 45 ± 13 years. Tumors were mostly in the lower extremities (92% [110 of 120]), most commonly in the knee (61% [73 of 120]) and ankle (18% [21 of 120]). As a secondary outcome, patients scored worst pain at the site of the tumor in the past 24 hours on an 11-point numeric rating scale (NRS). The primary definition of a pain response was a decrease of at least 30% in the weekly mean worst-pain NRS score and increase of less than 30% in narcotic analgesic use between baseline and week 25. Planned exploratory assessments of pain included the frequency of a pain response using alternative thresholds, including a decrease in worst-pain NRS score of 50% or more and a decrease of at least 2 points (minimum clinically important difference [MCID]), the magnitude of pain reduction between baseline and week 25, correlation between worst-pain NRS score and tumor shrinkage by RECIST 1.1 criteria, and the durability of the pain response during the open-label extension. Pain responses during the randomized portion of the trial were compared according to intention-to-treat analysis, with a one-sided threshold of p < 0.025 to reduce the risk of false-positive results. Pain assessment was complete for 59% (35 of 59) of patients in the placebo group and 54% (33 of 61) of patients in the pexidartinib group. Demographic and disease characteristics did not differ between the two treatment groups. RESULTS: A difference in the primary assessment of a pain response was not detected between pexidartinib and placebo (response percentage 31% [19 of 61] [95% CI 21% to 44%] versus 15% [9 of 59] [95% CI 8% to 27%]; one-sided p = 0.03). In the exploratory analyses, pexidartinib provided a modest improvement in pain (response percentage 26% [16 of 61] [95% CI 17% to 38%] versus 10% [6 of 59] [95% CI 5% to 20%]; one-sided p = 0.02 using the 50% threshold and 31% [19 of 61] [95% CI 21% to 44%] versus 14% [8 of 59] [95% CI 7% to 25%]; one-sided p = 0.02 using the MCID threshold). The least-squares mean change in the weekly mean worst-pain NRS score between baseline and week 25 was larger in patients treated with pexidartinib than placebo (-2.5 [95% CI -3.0 to -1.9] versus -0.3 [95% CI -0.9 to 0.3]; p < 0.001), although the mean difference between the two groups (-2.2 [95% CI -3.0 to -1.4]) was just over the MCID. Improvement in the weekly mean worst-pain NRS score correlated with the reduction in tumor size (r = 0.44; p < 0.001) and tumor volume score (r = 0.61; p < 0.001). For patients in the open-label extension, the change in the worst-pain NRS score from baseline was similar to the change at the end of the randomized portion and just above the MCID (mean -2.7 ± 2.2 after 25 weeks and -3.3 ± 1.7 after 50 weeks of receiving pexidartinib). CONCLUSION: Based on the current study, a modest reduction in pain, just larger than the MCID, may be an added benefit of pexidartinib in these patients, although the findings are insufficient to justify the routine use of pexidartinib for pain relief. LEVEL OF EVIDENCE: Level II, therapeutic study.

Psychometric validation and meaningful within-patient change of the Migraine-Specific Quality of Life questionnaire version 2.1 electronic patient-reported outcome in patients with episodic and chronic migraine.

OBJECTIVE: To evaluate the measurement properties of all three domains of the Migraine-Specific Quality of Life questionnaire version 2.1 (MSQ v2.1) electronic patient-reported outcome (ePRO) to assess the functional impact of migraine in patients with episodic or chronic migraine (CM); and identify meaningful within-patient change thresholds for the Role Function-Restrictive (RFR), Role Function-Preventive (RFP), and Emotional Function (EF) domains. METHODS: Data were drawn from three double-blind, placebo-controlled, and randomized Phase 3 clinical studies (episodic migraine [EM]: EVOLVE-1 and EVOLVE-2; CM: REGAIN). The psychometric properties of the MSQ v2.1 ePRO domains were demonstrated by evaluating reliability (internal consistency and test-retest), construct validity (convergent and known groups), and responsiveness. Meaningful within-patient change thresholds for domains were estimated using anchor-based approaches, supplemented by empirical cumulative distribution function curves and probability density function plots to enable interpretation of meaningful change over 3 months. The Patient Global Impression of Severity (PGI-S) and Patient Global Impression of Improvement served as anchors. RESULTS: A total of 2,850 patients with either EM (EVOLVE-1: 851; EVOLVE-2: 909) or CM (REGAIN: 1,090) were included. The Cronbach's alpha estimates of internal consistency exceeded the recommended threshold of ≥0.70 for all domains from the three studies, indicating adequate internal consistency. Test-retest reliability intraclass correlation coefficients were ≥0.80 for all domains across all three studies, demonstrating almost perfect agreement. Convergent validity was supported by moderate-to-strong correlation (r ≥ 0.30) between all domains of MSQ v2.1 ePRO and studied anchors (Migraine Disability Assessment Score and PGI-S scores) across all three studies. Known group validity was established between all domains and subgroups of patients stratified by baseline PGI-S scores and baseline number of monthly migraine headache days for all three studies. The 3-month meaningful within-patient change thresholds were the same for EM and CM for RFP: 20.00 and EF: 26.67; and for RFR: 25.71. CONCLUSIONS: These findings demonstrate that all three domains of the MSQ v2.1 ePRO have sufficient reliability, validity, responsiveness, and appropriate interpretation standards. Our results suggest that MSQ v2.1 ePRO is a well-defined and reliable patient-reported outcome instrument that is suitable for use in clinical studies for evaluating the impact of migraine on patient functioning in episodic and CM.

Pexidartinib improves physical functioning and stiffness in patients with tenosynovial giant cell tumor: results from the ENLIVEN randomized clinical trial.

Background and purpose - The ENLIVEN trial showed that, after 25 weeks, pexidartinib statistically significantly reduced tumor size more than placebo in patients with symptomatic, advanced tenosynovial giant cell tumor (TGCT) for whom surgery was not recommended. Here, we detail the effect of pexidartinib on patient-reported physical function and stiffness in ENLIVEN.Patients and methods - This was a planned analysis of patient-reported outcome data from ENLIVEN, a double-blinded, randomized phase 3 trial of adults with symptomatic, advanced TGCT treated with pexidartinib or placebo. Physical function was assessed using the Patient-Reported Outcomes Measurement Information System (PROMIS)-physical function (PF), and worst stiffness was assessed using a numerical rating scale (NRS). A mixed model for repeated measures was used to compare changes in PROMIS-PF and worst stiffness NRS scores from baseline to week 25 between treatment groups. Response rates for the PROMIS-PF and worst stiffness NRS at week 25 were calculated based on threshold estimates from reliable change index and anchor-based methods.Results - Between baseline and week 25, greater improvements in physical function and stiffness were experienced by patients receiving pexidartinib than patients receiving placebo (change in PROMIS-PF = 4.1 [95% confidence interval (CI) 1.8-6.3] vs. -0.9 [CI -3.0 to 1.2]; change in worst stiffness NRS = -2.5 [CI -3.0 to -1.9] vs. -0.3 [CI -0.9 to 0.3]). Patients receiving pexidartinib had higher response rates than patients receiving placebo for meaningful improvements in physical function and stiffness. Improvements were sustained after 50 weeks of pexidartinib treatment.Interpretation - Pexidartinib treatment provided sustained, meaningful improvements in physical function and stiffness for patients with symptomatic, advanced TGCT.

A Qualitative Study to Assess the Content Validity of the 24-Hour Migraine Quality of Life Questionnaire in Patients with Migraine.

OBJECTIVE: A concept elicitation, cognitive debriefing, and usability study was undertaken to: (1) explore migraine symptoms and day-to-day impacts; (2) determine the comprehensiveness and comprehensibility of the previously developed 24-Hour Migraine Quality of Life Questionnaire electronic patient-reported outcome (24-Hr MQoLQ ePRO) items, and the appropriateness and understanding of the recall period, response options, and instructions; and (3) assess the usability on an electronic hand-held device. METHODS: Eleven United States English-speaking people with episodic migraine were recruited to participate in one-on-one interviews, which followed methods appropriate for concept elicitation, cognitive debriefing, and usability testing. Interviews were audio-recorded, transcribed, and analyzed following the constant comparative method. RESULTS: Participants had a mean age of 42 years, and 8 were female. Through spontaneous mention or probing, all concepts of the 24-Hr MQoLQ ePRO were endorsed by a majority of the participants. Cognitive interviewing confirmed the 24-Hr MQoLQ ePRO instructions were clear, meaningful, and important to assess as symptoms and day-to-day impacts experienced as a result of migraine. Overall impressions of the ePRO device were overwhelmingly favorable, and the ePRO device was preferred to paper and pencil by all participants. Participant responses regarding the level of headache pain that would be acceptable in order to continue to go about daily activities ranged from 3 to 6, on a scale of 0 to 10, with 0 being "no headache" and 10 being "the worst headache." CONCLUSIONS: The 24-Hr MQoLQ ePRO is content-valid and appropriate for inclusion in future acute treatment for migraine studies designed to measure the symptoms and health-related quality of life of migraine.

Psychometric Validation of the Role Function Restrictive Domain of the Migraine Specific Quality-of-Life Questionnaire Version 2.1 Electronic Patient-Reported Outcome in Patients With Episodic and Chronic Migraine.

OBJECTIVES: To assess the measurement properties of the Migraine-Specific Quality of Life Questionnaire version 2.1 (MSQv2.1) electronic patient-reported outcome (ePRO) Role Function-Restrictive (RFR) domain to evaluate the functional impact of migraine in patients with episodic (EM) or chronic migraine (CM) enrolled in clinical trials. METHODS: The 7-item MSQv2.1 ePRO RFR measures the functional impact of migraine on relationships with family and friends, leisure time, work or daily activities, productivity, concentration, tiredness, and energy. Measurement properties of the RFR were assessed using data from 2 EM (CGAG [n = 851] and CGAH [n = 909]) and 1 CM (CGAI [n = 1090]) Phase 3 galcanezumab clinical trials. Anchor- and distribution-based analyses were utilized to derive a responder threshold for clinical interpretation of change over time. The Migraine Disability Assessment (MIDAS), Patient Global Impression of Severity (PGI-S), Patient Global Impression of Improvement (PGI-I), and migraine headache days (MHD) served as anchors. Responsiveness and responder threshold analyses were completed from baseline to the average of months 4-6 for EM studies, and from baseline to month 3 for the CM study; timeframes selected were based on the primary endpoints in these studies. RESULTS: Cronbach's alpha values for internal consistency reliability were 0.93, 0.92, and 0.92, for CGAG, CGAH, and CGAI, respectively. Test-retest reliability intra-class correlation coefficients were 0.82 and 0.84 for CGAG and CGAH, and 0.85 for CGAI in stable patients. Convergent validity was supported by moderate to strong correlations (≥0.30) between the RFR and both MIDAS and PGI-S. Known-groups validity was established between subgroups stratified by baseline PGI-S and MHD (P < .05; δ = 0.35-1.96). For the EM studies, anchor variables suggested a change of ≥25 points (equivalent to 9 points/state changes on raw scale) in the RFR was an appropriate threshold to interpret a treatment benefit. For the CM study a change of ≥17.14 points (6 points/state changes on raw scale) was an appropriate threshold. In all 3 studies, significantly (P < .01) more galcanezumab patients achieved the responder definition thresholds, as compared to placebo (odds ratios of 1.98, 2.45, 2.27, 2.44, 1.64, and 1.66 for the 120 and 240 mg arms in the CGAG, CGAH, and CGAI trials, respectively). CONCLUSION: The MSQv2.1 ePRO RFR has sufficient reliability, validity, responsiveness, and appropriate interpretation standards for use in EM and CM clinical trials to assess the functional impact of migraine.

Patient-reported outcomes and quality of life in advanced ALK+ non-small-cell lung cancer trial of brigatinib (ALTA).

Aim: Patient-reported outcomes (PRO) can support clinically relevant primary end points. Materials & methods: The ALTA trial, an open-label, Phase II, randomized dose-comparison study, evaluated the safety and efficacy of brigatinib in ALK+ non-small-cell lung cancer. PRO data collection included the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (QLQ-C30). A linear mixed model for repeated measures was used to analyze change from baseline in the Global Health Status/Quality of Life subscale (GHS/QOL), with a change of greater than or equal to ten points deemed meaningful. Results: Improvement in mean GHS/QOL scores was statistically significant in the majority of treatment cycles; <10% of patients experienced a meaningful worsening of their GHS/QOL and symptom scores. Conclusion: PRO-measured benefits are consistent with objective response benefits associated with brigatinib.

Comprehensive validation of the functional assessment of anorexia/cachexia therapy (FAACT) anorexia/cachexia subscale (A/CS) in lung cancer patients with involuntary weight loss.

PURPOSE: Comprehensive (qualitative and quantitative) assessments of the 12-item functional assessment of anorexia/cachexia therapy (FAACT) anorexia/cachexia subscale (A/CS) and relevant subscales were undertaken for use in constructing potential endpoints in clinical trials of non-small cell lung cancer (NSCLC) with involuntary weight loss. METHODS: Eleven participants (≥ 18 years) from six clinical sites with a diagnosis of stage III unresectable or stage IV NSCLC and involuntary weight loss (either ≥ 5% body weight loss within six months prior to screening or screening BMI < 20 kg/m2) were interviewed to evaluate the content validity of the A/CS domain. A psychometric evaluation was conducted on the A/CS domain, and symptoms and concerns subscales, using data from previously completed phase III clinical trials (ROMANA1 [N = 474] and ROMANA2 [N = 488]). RESULTS: Anorexia-related symptoms were highly relevant to participants and had important impacts on their lives including energy levels, and physical, social, and psychological functioning. The majority of participants endorsed the A/CS domain items and found them to be easily understood, relevant, and comprehensive. Confirmatory factor analyses established that the A/CS symptoms and concerns subscales provided an acceptable fit as single factor models in ROMANA1 and ROMANA2. Reliability, validity, and responsiveness were established for the 12item A/CS domain, 5item anorexia symptoms subscale, and 4-item anorexia concerns subscale. CONCLUSIONS: These scales have good content validity, favorable psychometric properties, and can be used for characterizing the effect of treatment on anorexia symptoms and/or anorexia-related concerns in patients with NSCLC.

Academic Anesthesiology Career Development: A Mixed-Methods Evaluation of the Role of Foundation for Anesthesiology Education and Research Funding.

BACKGROUND: In 1986, the American Society of Anesthesiologists created the Foundation for Anesthesiology Education and Research (FAER) to fund young anesthesiology investigators toward the goal of helping launch their academic careers. Determining the impact of the FAER grant program has been of importance. METHODS: This mixed-methods study included quantitative data collection through a Research Electronic Data Capture survey and curriculum vitae (CV) submission and qualitative interviews. CVs were abstracted for education history, faculty appointment(s), first and last author peer-reviewed publications, grant funding, and leadership positions. Survey nonrespondents were sent up to 3 reminders. Interview questions elicited details about the experience of submitting a FAER grant. Quantitative data were summarized descriptively, and qualitative data were analyzed with NVivo. RESULTS: Of 830 eligible participants, 38.3% (N = 318) completed surveys, 170 submitted CVs, and 21 participated in interviews. Roughly 85% held an academic appointment. Funded applicants were more likely than unfunded applicants to apply for National Institutes of Health funding (60% vs 35%, respectively; P < .01), but the probability of successfully receiving an National Institutes of Health grant did not differ (83% vs 85%, respectively; P = .82). The peer-reviewed publication rate (publications per year since attending medical school) did not differ between funded and unfunded applicants, with an estimated difference in means (95% confidence interval) of 1.3 (-0.3 to 2.9) publications per year. The primary FAER grant mentor for over one-third of interview participants was a nonanesthesiologist. Interview participants commonly discussed the value of having multiple mentors. Key mentor attributes mentioned were availability, guidance, reputation, and history of success. CONCLUSIONS: This cross-sectional data demonstrated career success in publications, grants, and leadership positions for faculty who apply for a FAER grant. A FAER grant application may be a marker for an anesthesiologist who is interested in pursuing a physician-scientist career.

Use of Survey and Delphi Process to Understand Trauma Anesthesia Care Practices.

BACKGROUND: Few trauma guidelines evaluate and recommend anesthesiology practices and there are no trauma anesthesia-specific guidelines. There is no information on how anesthesiologists perceive clinical practice patterns. Our objective was to understand the perceptions of anesthesiologists regarding trauma anesthesia practices. METHODS: A survey assessing anesthesia management of trauma patients was distributed to 21,491 anesthesiologists. A subset of 10 of these questions was subsequently reviewed by a trauma anesthesiology focus group through a 3-round web-based Delphi process. A question was deemed to have respondent consensus if the response with the highest percentage of agreement was unchanged between rounds 1 and 2. RESULTS: A total of 2360 anesthesiologists (11% response rate) responded to the survey. Results demonstrated that the practitioners' answers conflicted with existing surgical trauma society recommendations (ie, when to transfuse component therapy), and several areas that lacked any guidelines, resulted in response variability among anesthesiologists where not 1 answer achieved >75% agreement (ie, intubation technique of choice for patients with uncleared cervical spine). Thirteen trauma anesthesiologists participated in round 1 (response rate 100%), and 12 responded in rounds 2 and 3 (response rate 92%) of the Delphi process. None of the questions received 100% agreement. Consensus was achieved on 9 of 10 statements pertaining to trauma anesthesia care. Consensus was not reached on the intubating technique in a hemodynamically unstable patient with an uncleared cervical spine with deficits. Delphi participant opinion conflicted with existing guidelines on 2 statements: the use of cricoid pressure, and when to begin blood component therapy. CONCLUSIONS: There are several important areas of trauma anesthesia practice where guidelines do not exist and several where existing guidelines are not endorsed by the majority of practitioners who completed our survey. The lack of consensus on trauma anesthesia management and the variation in survey responses demonstrate a need to develop evidence-based trauma anesthesia guidelines.

Will Medicare Readmission Penalties Motivate Hospitals to Reduce Arthroplasty Readmissions?

BACKGROUND: The Centers for Medicare & Medicaid Services (CMS) recently imposed penalties against hospitals with above-average 30-day readmission rates following total joint arthroplasty (TJA). Hospitals must decide whether investments in readmission prevention are worthwhile. This study examines the financial incentives associated with unplanned readmissions before and after invocation of these penalties. METHODS: Financial data were reviewed for 2028 consecutive primary TJAs performed on Medicare beneficiaries over a 2-year period at an urban academic health system. Readmission penalties were estimated in accordance with CMS policies. RESULTS: Unplanned readmissions generated a $4416 median contribution margin. The initial hospitalizations (when the TJA was performed) were financially unfavorable for patients subsequently readmitted relative to those not readmitted due to increased costs of care (P = .002), but these costs were more than outweighed by the increased reimbursement earned during the readmission (P < .001), ultimately making readmitted patients financially preferable (P < .001). Going forward, penalties will be levied for risk-adjusted readmission rates above the national rate of 4.8%. For the institution under review, the penalty per readmission outweighs the financial gains earned through readmission by $12,184, resulting in a net loss from readmissions if the rate exceeds 6.5%. It will be financially optimal to maintain a readmission rate (after risk adjustment) equal to the national average but exceeding that rate will be $7768 more expensive per readmission than undershooting that target. CONCLUSION: If our results are generalizable, unplanned Medicare readmissions have traditionally been financially beneficial, but CMS penalties outweigh this benefit. Thus, penalties should incentivize institutions to maintain below-average arthroplasty readmissions rates.

The QTc effect of low-dose methadone for chronic pain: a prospective pilot study.

OBJECTIVE: Methadone is associated with QT prolongation and serious cardiac complications, but this has been primarily demonstrated in opioid dependent patients receiving moderate to high doses. This study investigates the effect of low-dose methadone on the QTc interval in a chronic pain population. DESIGN AND SUBJECTS: We conducted a prospective cohort study in a chronic pain clinic including 82 patients receiving methadone and 102 patients receiving non-methadone opioid therapy. METHODS: We analyzed automated QTc calculations from 12-lead electrocardiograms at baseline and during the subsequent 6 months. The primary outcome of interest was the incidence of QTc greater than 470 milliseconds or an increase from baseline of greater than 60 milliseconds. RESULTS: The methadone group did not manifest an overall higher frequency of QTc > 470 milliseconds (6% for the methadone group vs 5% for controls, P = 0.722) or an increase in the QTc of > 60 milliseconds (4% for the methadone group vs 4% for controls, P = 0.94). In the first month after initiating methadone, patients demonstrated an increase in QTc compared to controls (5% for the methadone group vs 0% for the controls, P = 0.073) but the difference disappeared in the third and sixth months. CONCLUSION: Data from our chronic pain clinic support a potential association of QTc prolongation during the initiation of methadone, but this effect is small and short lived. We believe larger scale studies to further characterize the safety profile of low-dose methadone are warranted.

Physical activity and telomere length in early stage breast cancer survivors.

INTRODUCTION: Telomere length (TL) is a biomarker of accumulated cellular damage and human aging. Evidence in healthy populations suggests that TL is impacted by a host of psychosocial and lifestyle factors, including physical activity. This is the first study to evaluate the relationship between self-reported physical activity and telomere length in early stage breast cancer survivors. METHODS: A cross-sectional sample of 392 postmenopausal women with stage I-III breast cancer at an outpatient oncology clinic of a large university hospital completed questionnaires and provided a blood sample. TL was determined using terminal restriction fragment length analysis of genomic DNA isolated from peripheral blood mononuclear cells. Physical activity was dichotomized into two groups (none versus moderate to vigorous) using the International Physical Activity Questionnaire. Multivariate linear and logistic regression analyses were performed to identify factors associated with mean TL and physical activity. RESULTS: Among participants, 66 (17%) did not participate in any physical activity. In multivariate model adjusted for age, compared to those who participated in moderate to vigorous physical activity, women who participated in no physical activity had significantly shorter TL (adjusted coefficient ß=-0.22; 95% confidence interval (CI), -0.41 to -0.03; P=.03). Non-white race, lower education and depressive symptoms were associated with lack of self-reported physical activity (P<0.05 for all) but not TL. CONCLUSION: Lack of physical activity is associated with shortened TL, warranting prospective investigation of the potential role of physical activity on cellular aging in breast cancer survivors.

What are the economic consequences of unplanned readmissions after TKA?

BACKGROUND: In 2009, the Center for Medicare & Medicaid Services (CMS) began penalizing hospitals with high rates of 30-day readmissions after hospitalizations for certain conditions. This policy will expand to include TKA in 2015. QUESTIONS/PURPOSES: What are the median profits and contribution margins of: (1) Medicare-reimbursed TKA, (2) 30-day TKA readmission, and (3) entire episode of care for readmitted TKA patients within 30 days compared to nonreadmitted patients? (4) Under new CMS guidelines, what financial penalty will the authors' institution face if its arthroplasty readmission rate exceeds the national average? METHODS: A retrospective review of 3218 primary TKAs performed during 2 years at a large urban academic hospital network was conducted using administrative and financial data. RESULTS: The median profit and contribution margins, respectively, were as follows: TKA episode, USD 5209 and USD 11,726; 30-day readmission, USD 608 and USD 3814; TKA visit with readmission, USD 2855 and USD 13,901; TKA visit without readmission, USD 5300 and USD 11,652. Readmission penalties could reach USD 6.21 million per year for the authors' institution. DISCUSSION: If our results are generalizable, unplanned TKA readmissions lead to diminished total profit. Although associated with a positive contribution margin, this is likely to be a short-term phenomenon as the new CMS policy will result in readmissions coming at a steep cost to referral centers.

Development of a professionalism committee approach to address unprofessional medical staff behavior at an academic medical center.

BACKGROUND: The Joint Commission Leadership standard on the need to create and maintain a culture of safety and quality and to develop a code of conduct was based on the rationale that unprofessional behavior undermines a culture of safety and can thereby be harmful to patient care. Few reports have described effective and successful approaches to defining and managing unprofessional behavior. The Professionalism Committee (PC)-based approach at the University of Pennsylvania Health System (UPHS) may serve as a model for other hospitals and health systems. METHODS: Each of the three large teaching hospitals within UPHS has a PC that reports to its respective Medical Executive Committee. The PCs serve as a resource for department chairs and hospital administrators to address unprofessional behavior among faculty. Key features of the PC include the PC chair as the first point of contact and the integration of psychiatry into the model by virtue of the Professionalism Committee chair's training and expertise in psychiatry. RESULTS: In the 2009 calendar year, the PC chair received contacts concerning behavior of only 2 physicians, which increased to 42 physicians in 2011 and 39 in 2012. Contacts involved referrals, management consults, interview screening, and the need for general advice. Of 79 resolved cases, 30 involved interpersonal issues, and 2 were associated with poor clinical outcomes. CONCLUSION: One key feature of the UPHS approach is early identification of the role of behavioral health issues in unprofessional behavior (as opposed to physical, cognitive, or systems issues) by virtue of the PC chair's professional training and expertise. Although aspects of the UPHS experience may not be generalizable, the PC structure and approach are replicable.

Are there identifiable risk factors and causes associated with unplanned readmissions following total knee arthroplasty?

We conducted a retrospective review of 3218 primary total knee arthroplasties (TKA) performed over two years at an urban academic hospital network using clinical and administrative data. Increased length of stay (LOS) was associated with readmission (P < 0.001). Readmission was not associated with age (P = 0.100), gender (P = 0.608), body mass index (P = 0.329), or staged bilateral procedures (P = 0.420). The most common readmitting diagnoses were post-operative infection (22.5%), hematoma (10.1%), pulmonary embolus (7.9%) and deep vein thrombosis (5.6%). Of readmissions, 53.9% were for surgical reasons and 46.1% were for medical reasons. Certain interventions described in previous literature may be more successful in minimizing unplanned readmissions by focusing on patients with extended LOS, elevated infection risk and low socioeconomic status.

Significantly reduced hypoxemic events in morbidly obese patients undergoing gastrointestinal endoscopy: Predictors and practice effect.

BACKGROUND: Providing anesthesia for gastrointestinal (GI) endoscopy procedures in morbidly obese patients is a challenge for a variety of reasons. The negative impact of obesity on the respiratory system combined with a need to share the upper airway and necessity to preserve the spontaneous ventilation, together add to difficulties. MATERIALS AND METHODS: This retrospective cohort study included patients with a body mass index (BMI) >40 kg/m(2) that underwent out-patient GI endoscopy between September 2010 and February 2011. Patient data was analyzed for procedure, airway management technique as well as hypoxemic and cardiovascular events. RESULTS: A total of 119 patients met the inclusion criteria. Our innovative airway management technique resulted in a lower rate of intraoperative hypoxemic events compared with any published data available. Frequency of desaturation episodes showed statistically significant relation to previous history of obstructive sleep apnea (OSA). These desaturation episodes were found to be statistically independent of increasing BMI of patients. CONCLUSION: Pre-operative history of OSA irrespective of associated BMI values can be potentially used as a predictor of intra-procedural desaturation. With suitable modification of anesthesia technique, it is possible to reduce the incidence of adverse respiratory events in morbidly obese patients undergoing GI endoscopy procedures, thereby avoiding the need for endotracheal intubation.

Taste alteration in breast cancer patients treated with taxane chemotherapy: experience, effect, and coping strategies.

PURPOSE: This study examined the experience and coping strategies for taste alteration in female breast cancer patients treated with docetaxel or paclitaxel. METHODS: A purposive sample of 25 patients currently receiving docetaxel or paclitaxel or within 6 months of having completed treatment was recruited. Semi-structured interviews and patient-level data were utilized for this exploratory descriptive study. Interview data were analyzed with the constant comparative method; patient-level data were abstracted from the electronic medical record. RESULTS: Of all side effects reported from taxanes, the most common was taste alteration (8 of 10 docetaxel patients, 3 of 15 paclitaxel patients). Women that experience taste alteration chose not to eat as much, ate on an irregular schedule, and/or lost interest in preparing meals for themselves and/or their family. Women adopted a variety of new behaviors to deal with the taste alteration and its effects, including trying new recipes, eating strongly flavored foods, honoring specific food cravings, eating candy before meals, cutting food with lemon, drinking sweetened drinks, using plastic eating utensils, drinking from a straw, brushing their teeth and tongue before meals, and using baking soda and salt wash or antibacterial mouthwash. CONCLUSIONS: Taste alteration affects breast cancer patients' lives, and they develop management strategies to deal with the effect. While some self-management strategies can be seen as positively adaptive, the potential for increased caloric consumption and poor eating behaviors associated with some coping strategies may be a cause for concern given the observation of weight gain during breast cancer treatment and association of obesity with poor treatment outcomes in breast cancer patients. Further studies are warranted to determine the overall burden of this symptom and measurement of cancer and non-cancer-related consequences of these behavioral adaptations.

Analysis of field reports from anaesthesia volunteers in low- to middle-income countries.

OBJECTIVES: The objective of this study was to identify key experiences and common motifs of volunteer doctors who have participated in anaesthesia-related volunteer experiences abroad through the Health Volunteers Overseas (HVO) programme. An additional goal was to understand the effects of medical volunteerism in developing countries on the volunteers themselves. METHODS: After a medical mission with HVO, anaesthesia volunteers submit a post-experience report. Twenty-five reports were randomly selected from the 58 available trip reports, including five from each of the five countries collaborating with HVO. Data in the reports were analysed using a modified grounded theory and constant comparative technique until thematic saturation was achieved. RESULTS: Three major discoveries emerged from the analysis of post-experience reports: (i) anaesthesia residents and attending physicians find their volunteer experiences in the developing world to be personally rewarding and positive; (ii) most participants feel their educational interventions have a positive impact on local students and anaesthesia providers, and (iii) global volunteerism poses challenges, primarily caused by lack of resource availability and communication issues. CONCLUSIONS: Our results give new insight into the experiences of and challenges faced by a cohort of HVO-sponsored anaesthesia volunteers while abroad and validates the positive effects these global health experiences have on the volunteers themselves. This group of anaesthesia volunteers was able to further their personal and professional growth, sharpen their physical diagnosis and clinical reasoning skills in resource-poor environments and, most importantly, provide education and promote an exchange of ideas and information.

Impact of guideline implementation on transfusion practices in a surgical intensive care unit.

BACKGROUND: Anemia is a common clinical problem in cardiac surgery patients in the postoperative period and may result in transfusion in up to 90% of this population. There is tremendous variation in transfusion rates by hospital and individual physician. It is unknown if implementation of a clinical practice guideline lowers unnecessary transfusion in hospital practices that already have a restrictive transfusion culture . OBJECTIVE: To evaluate transfusion practice before and after implementation of a clinical practice guideline. DESIGN: Pre/post intervention study. SETTING: Sixteen bed surgical intensive care unit in an academic hospital. PARTICIPANTS: Four hundred ninety-five adult patients undergoing cardiac surgery. INTERVENTIONS: Implementation of an anemia clinical practice guideline reinforced with education and retrospective audit/feedback. MEASUREMENTS AND MAIN RESULTS: A total of 252 pre-intervention and 243 postintervention cases were examined. Unnecessary transfusion occurred in 14.7% of pre-intervention patients and decreased to a rate of 8.1% after guideline implementation (p = 0.016). CONCLUSIONS: This study suggests that clinical guideline implementation utilizing guideline development, education, and compliance audit/feedback may reduce unnecessary transfusion in cardiac surgery patients. A fully powered prospective trial would be necessary to validate these findings.