Search

This is a tutorial on designing a persuasive pilot study of a psychosocial intervention (e.g., behavioral symptom management) in the palliative care setting. This tutorial is most relevant for early stages of intervention research that aims to progress toward a randomized controlled trial with a high degree of internal validity. Broadly, a pilot study aims to address multiple elements of feasibility and acceptability so that investigators are well positioned for the next study in their program of research. To assist investigators in writing compelling grant applications we designed this tutorial as an annotated checklist of goals that a pilot study within the palliative care domain should seek to accomplish. These goals include the following: 1) begin with the end in mind, 2) use a formal conceptual model, 3) use measures with strong psychometric properties, 4) justify the timing of study sessions and assessments, 5) test recruitment methods, 6) estimate retention, 7) assess interventionist fidelity, 8) assess acceptability of the intervention, 9) assess feasibility, and 10) identify barriers to the next study. We elaborate on these goals by describing an ongoing pilot study testing the feasibility and acceptability of a psychosocial pain management intervention for patients with advanced cancer. Pilot studies are crucial for building a successful program of research, but they are also limited in terms of their sample size and overall objectives. A persuasive pilot study is one that is limited yet useful rather than limited and trivial.

Questionable research practices (QRP) are actions taken by researchers that span a range of concern related to violation of research best practices, and ultimately expose institutions and research participants to risk. Numerous studies have shown that QRP are common. The continued prevalence of QRP indicates that existing approaches for dealing with QRP are falling short. In this editorial we discuss the risks associated with QRP and propose mitigation strategies at the institutional level using a common QRP as an example, questionable treatment of subgroup analyses. We argue that the need for institutional intervention in cases such as this are particularly motivating when both the investigator and the institution have a substantial financial conflict of interest related to intellectual property that requires the investigator's expertise to continue developing. To address this, we propose an expansion of the traditional conflict of interest management process.

Acute myeloid leukemia (AML) is a hematologic malignancy characterized by a poor prognosis but also a paradoxical possibility of cure. This renders decision-making complex and imminent. Unfortunately, many patients with AML misestimate their prognosis and treatment risk. While decision aids can improve illness understanding and reduce decisional conflict, there are no validated decision aids for AML. We developed and tested a novel AML decision aid (NCT03442452). Patients (n = 20) were recruited at Duke University from May 2018 to February 2019. Participants completed assessments of AML knowledge and decisional conflict, before and after using the electronic decision aid. The primary endpoint was feasibility (endpoint met if > 80% of study participants completed all study components). Secondary analyses of efficacy were conducted using paired t tests for dependent pre-/post-samples. The primary endpoint of feasibility was met (100% of participants completed all study components). Secondary analyses showed improved knowledge and reduced decisional conflict after using the decision aid. Knowledge scores improved from a mean of 11.8 (out of 18) correct items at baseline to 15.1 correct items after using the decision aid (mean difference 3.35; p < 0.0001). Decisional conflict scores reduced significantly from baseline to post-test as well (mean difference − 6.5; p = 0.02). These findings suggest that our AML decision aid is a useful tool to improve the patient experience and promote shared decision-making in AML. A randomized efficacy trial is planned.

Background Approximately 38% of patients with colorectal cancer will develop isolated liver metastases. Sidedness of colon tumor is identified in non-metastatic and unresected metastatic cancers as predictive of survival, yet its dedicated analysis in resected liver metastases is minimal. Our primary aim was to assess whether left-sided primary tumors improve prognosis in stage IV cancer patients undergoing curative-intent liver metastasectomy; it was hypothesized that it would. Methods This is a retrospective, observational cohort study from 1996 to 2016 in a single tertiary-care facility. Survival from diagnosis was calculated via Kaplan–Meier method and compared between the right and left sides via log-rank analysis. Results Median survival differs significantly between colorectal tumors of the right and left origins after hepatic metastasectomy in 612 patients. In patients with right-sided tumors, median survival from diagnosis was 4.5 years (IQR 4.1–5.3), and 6.3 years (IQR 5.6–6.9) in those with left tumors (HR 1.5, 95% CI 1.38–1.60, p Conclusion As in studies on earlier-stage or unresected metastatic disease, tumor sidedness is an important prognostic factor in patient survival with liver metastasectomy. Clinical risk scores should include side of primary tumor. Further work is needed to determine the molecular basis for this difference.

Background/Aims Pain is a major concern of patients with advanced cancer and their caregivers. There is strong evidence that pain coping skills training interventions based on cognitive-behavioral principles can reduce pain severity and pain interference. However, few such interventions have been tested for patients with advanced cancer and their family caregivers. This study aims to test the efficacy of a caregiver-guided pain coping skills training protocol on patient and caregiver outcomes. Methods A total of 214 patients age ≥18 with Stage III–Stage IV cancer and moderate to severe pain, along with their family caregivers, are being identified and randomized with a 1:1 allocation to the caregiver-guided pain coping skills training intervention or enhanced treatment-as-usual. Dyads in both conditions receive educational resources on pain management, and the caregiver-guided pain coping skills training intervention includes three weekly 60-min sessions conducted with the patient–caregiver dyad via videoconference. Measures of caregiver outcomes (self-efficacy for helping the patient manage pain, caregiver strain, caregiving satisfaction, psychological distress) and patient outcomes (self-efficacy for pain management, pain intensity and interference, psychological distress) are collected at baseline and post-intervention. Caregiver outcomes are also collected 3 and 6 months following the patient’s death. The study is enrolling patients from four tertiary care academic medical centers and one free-standing hospice and palliative care organization. The primary outcome is caregiver self-efficacy for helping the patient manage pain. Results This article describes challenges in the design and implementation of the CaringPals trial. Key issues for trial design include the identification and recruitment of patients with advanced cancer and pain, and the follow-up and collection of data from caregivers following the patient’s death. Conclusion The CaringPals trial addresses a gap in research in pain coping skills training interventions by addressing the unique needs of patients with advanced cancer and their caregivers. Findings from this study may lead to advances in the clinical care of patients with advanced cancer and pain, as well as a better understanding of the effects of training family caregivers to help patients cope with pain.

This communication describes the process and results of a curriculum review of a first-year sequence of courses in statistical inference within a Master of Biostatistics program. Our primary aim was to develop an innovative course in statistical theory that meets the needs of a diverse student audience, the majority of whom are seeking a terminal master’s degree while a minority will pursue PhD training in biostatistics. The main results were (1) different course paths for job-bound and PhD-bound students; and (2) the development of an innovative first course in statistical inference, which is a computationally-aided self-discovery of a salient (albeit not comprehensive) set of key concepts and techniques pertaining to statistical inference. The redesign process addressed a key conceptual barrier: namely, the unexamined assumption that deductive proofs are a necessary condition for rigorous presentation. Consistent with the principles of constructivism, we navigated this barrier by redefining the task to which pedagogic rigor should be applied: namely, to help students to develop a sound mental map of statistical inference. We believe that the approach we used to accomplish this redefined task could be generalized to additional aspects of statistical education, among others.

Student evaluation is a key consideration for educational program administrators because program success depends on students’ ability to demonstrate successful development of core competencies. Student evaluations must therefore be aligned with learning objectives and overall program goals. Graduate level educational programs typically incorporate course-level and program-level evaluations, e.g., a final examination in a single course vs. a qualifying examination that assesses knowledge gained from several courses. While there is often considerable attention given to the structure of these evaluations at the program level, the format is typically left to the instructor’s discretion. We argue in this article that there are administrative advantages to encouraging instructors to adopt creative forms of assessment that extend beyond the typical concerns related to program structure. Specifically, we argue that advantages can be gained in terms of increasing student engagement, adding real world context to student evaluations, maintaining positive program culture, and reducing the opportunity for cheating. We present two examples of creative assessments implemented in a 2-year Master of Biostatistics program, along with a discussion of three key questions administrators should consider as they work with instructors to develop innovative assessment methods: (1) what changes to make; (2) in what order to make those changes; and (3) how to consult with instructors about making those changes.

Acute myeloid leukemia (AML) is a hematologic malignancy characterized by a poor prognosis but also a paradoxical possibility of cure. This renders decision-making complex and imminent. Unfortunately, many patients with AML misestimate their prognosis and treatment risk. While decision aids can improve illness understanding and reduce decisional conflict, there are no validated decision aids for AML. We developed and tested a novel AML decision aid (NCT03442452).Patients (n = 20) were recruited at Duke University from May 2018 to February 2019. Participants completed assessments of AML knowledge and decisional conflict, before and after using the electronic decision aid. The primary endpoint was feasibility (endpoint met if80% of study participants completed all study components). Secondary analyses of efficacy were conducted using paired t tests for dependent pre-/post-samples.The primary endpoint of feasibility was met (100% of participants completed all study components). Secondary analyses showed improved knowledge and reduced decisional conflict after using the decision aid. Knowledge scores improved from a mean of 11.8 (out of 18) correct items at baseline to 15.1 correct items after using the decision aid (mean difference 3.35; p0.0001). Decisional conflict scores reduced significantly from baseline to post-test as well (mean difference - 6.5; p = 0.02).These findings suggest that our AML decision aid is a useful tool to improve the patient experience and promote shared decision-making in AML. A randomized efficacy trial is planned.

This is a short tutorial on two key questions that pertain to cluster randomized trials (CRTs): 1) Should I perform a CRT? and 2) If so, how do I derive the sample size? In summary, a CRT is the best option when you “must” (e.g., the intervention can only be administered to a group) or you “should” (e.g., because of issues such as feasibility and contamination). CRTs are less statistically efficient and usually more logistically complex than individually randomized trials, and so reviewing the rationale for their use is critical. The most straightforward approach to the sample size calculation is to first perform the calculation as if the design were randomized at the level of the patient and then to inflate this sample size by multiplying by the “design effect”, which quantifies the degree to which responses within a cluster are similar to one another. Although trials with large numbers of small clusters are more statistically efficient than those with a few large clusters, trials with large clusters can be more feasible. Also, if results are to be compared across individual sites, then sufficient sample size will be required to attain adequate precision within each site. Sample size calculations should include sensitivity analyses, as inputs from the literature can lack precision. Collaborating with a statistician is essential. To illustrate these points, we describe an ongoing CRT testing a mobile-based app to systematically engage families of intensive care unit patients and help intensive care unit clinicians deliver needs-targeted palliative care.

BACKGROUND Adoption of HIV pre-exposure prophylaxis (PrEP) remains limited among populations at greatest risk for HIV acquisition. This study aims to assess awareness of PrEP among individuals in Durham, North Carolina, which has one of the highest rates of HIV diagnoses in the state.METHOD In 2015-2016, we administered a survey including questions to assess PrEP awareness to individuals at multiple venues throughout Durham, North Carolina.RESULTS A total of 139 respondents were surveyed. The majority were male (66%) and black/African American (75%); 21% were Hispanic/Latino. There were an estimated 53 men who have sex with men (MSM), of which 18 (33%) were black MSM M 24 years of age. Overall, only 53/138 (38%) respondents were aware of PrEP. Awareness was reported among 33/52 (63%) MSM respondents, 29/46 (63%) black MSM, and 10/17 (59%) black MSM M 24 years of age. In multivariate analysis, non-heterosexual orientation, health-insured status, and prior HIV testing were significantly associated with PrEP awareness. Ninety-four (69%) of 137 respondents reported prior HIV testing.LIMITATIONS Limitations include non-random sampling and limited sample size. Further research needs to be done in other areas of North Carolina, and assessment of PrEP acceptability and uptake needs to be performed.CONCLUSION This study reveals low overall awareness of PrEP in Durham, North Carolina, indicating that expanded outreach is necessary to increase public awareness and encourage adoption of PrEP among all demographics at risk for HIV.

Conflict of interest (COI) and conflict of commitment (COC) are similar in that both concern the "risk that professional judgment or actions regarding a primary interest will be unduly influenced by a secondary interest" (Institute of Medicine). The Institute of Medicine recommends that the circumstances, risks, and evaluative frameworks for COI and COC warrant separate consideration. Here, we discuss some principles (and thus an evaluative framework) underlying COC and hope to provide a clarifying framework which extends across institutions. We propose that: An institution should become concerned about relationships, whether considered individually or as a whole, which because of the amount of the time commitment and/or the amount of the monetary compensation, potentially induces a dual loyalty or otherwise calls into question the ability of the faculty member to discharge their primary responsibility to the institution. The impact of single relationships on single actions constitutes COI; the net impact of multiple relationships and/or the overall ability to fully discharge primary institutional responsibilities constitutes COC.

We describe an innovative preorientation curriculum (POC) for a Master of Biostatistics (MB) program. The goal of the POC is to fill critical skills gaps for students entering the MB program from heterogeneous backgrounds so they are prepared to engage in the program’s rigorous, fast-paced training upon arrival. To achieve this goal, we introduce a structured approach to thinking that forms the foundation of a sound mental map of Biostatistics, which will assist students in their subsequent efforts to master the discipline. Based on constructivist principles, the POC covers mathematical and statistical theory, data analysis methods, programming, and statistical practice through a sequence of instruction that encourages reflection, extension, and connection between topics. The POC is modular, self-paced, and offered online via a cloud-hosted interactive learning management system (LMS). Students are required to complete the curriculum prior to the MB program orientation. We describe the rationale, design, features, and initial evaluation of the POC. Finally, to help programs interested in designing similar curricula, we provide a detailed instruction sequence description of one topic.

We describe an innovative, semester-long course in biology and communication skills for master’s degree students in biostatistics. The primary goal of the course is to make the connection between biological science and statistics more explicit. The secondary goals are to teach oral and written communication skills in an appropriate context for applied biostatisticians, and to teach a structured approach to thinking that enables students to become lifelong learners in biology, study design, and the application of statistics to biomedical research. Critical evaluation of medical literature is the method used to teach biology and communication. Exercises are constructivist in nature, designed to be hands-on and encourage reflection through writing and oral communication. A single disease area (cancer) provides a motivating example to: 1) introduce students to the most commonly used study designs in medical and public health research, 2) illustrate how study design is used to address questions about human biology and disease, 3) teach basic biological concepts necessary for a successful career in biostatistics, and 4) train students to read and critically evaluate publications in peer-reviewed journals. We describe the design and features of the course, the intended audience, and provide detailed examples for instructors interested in designing similar courses.

Purpose Routinely collected patient-reported outcomes (PROs) could provide invaluable data to a patient-centered learning health system but are often highly missing in clinical trials. We analyzed our experience with PROs to understand patterns of missing data using electronic collection as part of routine clinical care. Methods This is an analysis of a prospectively collected observational database of electronic PROs captured as part of routine clinical care in four different outpatient oncology clinics at an academic referral center. Results More than 24,000 clinical encounters from 7,655 unique patients are included. Data were collected via an electronic tablet–based survey instrument (Patient Care Monitor, version 2.0), at the time of clinical care, as part of routine care processes. Missing instruments (ie, no items completed) were submitted for 6.8% of clinical encounters, and 15.8% of encounters had missing items. Nearly 90% of all encounters involved < 10% missing items. In multivariable analyses, younger age, private health insurance, being seen in the breast oncology clinic, less time spent on the instrument, and longitudinal care were significantly associated with less missingness. Conclusion Embedding collection of electronic PRO data into routine clinical care yielded low rates of missing data in this real-world, prospectively collected database. In contrast to clinical trial experience, missingness improve with longitudinal care. This approach may be a solution to minimizing missingness of PROs in research or clinical care settings in support of learning health care systems.

Evaluate association between baseline quality of life (QOL) and changes in QOL measured by FACT-O TOI with progression-free disease (PFS) and overall survival (OS) in advanced epithelial ovarian cancer (EOC).Patients enrolled in GOG-0218 with completed FACT-O TOI assessments at baseline and at least one follow-up assessment were eligible. Baseline FACT-O TOI scores were sorted by quartiles (Q1-4) and outcomes compared between Q1 and Q2-4 with log-rank statistic and multivariate Cox regression adjusting for age, stage, post-surgical residual disease size, and performance status (PS). Trends in FACT-O TOI scores from baseline to the latest follow-up assessment were evaluated for impact on intragroup (Q1 or Q2-4) outcome by log-rank analysis.Of 1152 eligible patients, 283 formed Q1 and 869 formed Q2-4. Mean baseline FACT-O TOI scores were 47.5 for Q1 vs. 74.7 for Q2-4 (P0.001). Q1 compared to Q2-4 had worse median OS (37.5 vs. 45.6months, P=0.001) and worse median PFS (12.5 vs. 13.1months, P=0.096). Q2-4 patients had decreased risks of disease progression (HR 0.974, 95% CI 0.953-0.995, P=0.018), and death (HR 0.963, 95% CI 0.939-0.987, P=0.003) for each five-point increase in baseline FACT-O TOI. Improving versus worsening trends in FACT-O TOI scores were associated with longer median PFS (Q1: 12.7 vs. 8.6months, P=0.001; Q2-4: 16.7 vs. 11.1months, P0.001) and median OS (Q1: 40.8 vs. 16months, P0.001; Q2-4: 54.4 vs. 33.6months, P0.001).Baseline FACT-O TOI scores were independently prognostic of PFS and OS while improving compared to worsening QOL was associated with significantly better PFS and OS in women with EOC.

PURPOSE: Utilization of electronic patient-reported outcomes (ePROs) in the clinic can improve quality of life and prolong survival in cancer care. However, there remain unanswered questions regarding trends in missing data and the potential effect on real-time patient care. METHODS: This study utilized a prospectively collected dataset of ePROs from oncology clinics that administered the Patient Care Monitor 2.0 (PCM), a validated symptoms survey assessing 78 items for men, and 86 for women. We tabulated the frequency of missing items, by item and domain (emotional, functional and physical symptom-related), and examined these by age, gender, education, race and marital status. RESULTS: Within 20,986 encounters, there were responses to at least 1 PCM item from 6,933 unique patients. The highest frequency of missing answers occurred for: “attend a paid job” (10.7%), “reduced sexual enjoyment” (3.8%), and “run” (3.7%). By domain, 12.3% of functional, 8.4% of physical symptom-related, and 1.6% of emotional constructs contained at least one missing item. For functional and physical symptom-related items, missingness was most common in patients >60 years old. CONCLUSION: The frequency of missingness was highest for functional items, like attending a paid job, suggesting that some respondents (e.g., retirees without a paid job) skipped questions that were less applicable to them. More universal issues for cancer patients, such as emotional well-being, had much lower frequencies of missingness. This suggests differential item completion that warrants further study to understand the inherent drivers. Identifying causes of missingness could improve the clinical utility of ePROs and highlight opportunities to personalize care.

We consider the question of why (primarily) and how (secondarily) to perform scientific oversight of research performed by investigators with a financial conflict of interest (COI). One way to frame the trade-off of having investigators with financial COI participate in research is through a decision rule: "

Academic medical centers rarely require all of their research faculty and staff to participate in educational programs on the responsible conduct of research (RCR). There is also little published evidence of RCR programs addressing high-profile, internal cases of misconduct as a way of promoting deliberation and learning. In the wake of major research misconduct, Duke University School of Medicine (DUSoM) expanded its RCR education activities to include all DUSoM faculty and staff engaged in research. The program included formal deliberation of the Translational Omics misconduct case, which occurred at Duke. Over 5,000 DUSoM faculty and staff participated in the first phase of this new program, with a 100% completion rate. The article reports on the program's development, challenges and successes, and future directions. This experience at Duke University illustrates that, although challenging and resource intensive, engagement with RCR activities can be integrated into programs for all research faculty and staff. Formal, participatory deliberation of recent cases of internal misconduct can add a novel dimension of reflection and openness to RCR educational activities.

Background Women with breast cancer in medically underserved areas are particularly vulnerable to persistent pain and disability. Behavioral pain interventions reduce pain and improve outcomes. Cancer patients in medically underserved areas receive limited adjunctive cancer care, as many lack access to pain therapists trained in behavioral interventions, face travel barriers to regional medical centers, and may have low literacy and limited resources. mHealth technologies have the potential to decrease barriers but must be carefully adapted for, and efficacy-tested with, medically underserved patients. We developed an mHealth behavioral pain coping skills training intervention (mPCST-Community). We now utilize a multisite randomized controlled trial to: 1) test the extent mPCST-Community reduces breast cancer patients' pain severity (primary outcome), pain interference, fatigue, physical disability, and psychological distress; 2) examine potential mediators of intervention effects; and 3) evaluate the intervention's cost and cost-effectiveness. Methods/design Breast cancer patients (N = 180) will be randomized to mPCST-Community or an attention control. mPCST-Community's four-session protocol will be delivered via videoconferencing at an underserved community clinic by a remote pain therapist at a major medical center. Videoconference sessions will be supplemented with a mobile application. Participants will complete self-report measures at baseline, post-intervention, and 3- and 6-month follow-ups. Conclusions mPCST-Community has the potential to reduce pain and disability, and decrease barriers for cancer patients in medically underserved areas. This is one of the first trials to test an mHealth behavioral cancer pain intervention developed specifically for medically underserved communities. If successful, it could lead to widespread implementation and decreased health disparities.

Objective: Our master's program in biostatistics requires a qualifying examination (QE). A curriculum review led us to question whether to replace a closed-book format with an open-book one. Our goal was to improve the QE. Methods: This is a case study and commentary, where we describe the evolution of the QE, both in its goals and its content. The result was a week-long, open-book, collaborative, take-home examination structured around the analysis of two types of studies commonly encountered in biostatistical practice. Our evaluation of the revised format includes its fairness, student performance, and student feedback. Results: The new format has a number of advantages: (1) it has a specific educational goal; (2) it provides sufficient time for students to produce their best work; (3) it encourages students to review elements of the first-year curriculum as needed; and (4) it can be administered remotely, even during a pandemic. Potential concerns pertaining to cheating and rigor can be adequately addressed. The results of our evaluation of the examination have been encouraging. The QE is intended to be a "fair" examination that covers important material which is beneficial to students, and does so in a way that is transparent and puts everyone in a position to perform their best work. Conclusions: An examination using this format has much to recommend it. When designing an examination, it is important to (a) match its format with clearly specified educational goals; and (b) distinguish between the distinct constructs of difficulty and rigor.

Biostatisticians apply statistical methods to solve problems in the biological sciences. Successful practioners of biostatistics have advanced technical knowledge, are skilled communicators, and can seamlesslessly integrate with interdisciplinary scientific teams. Despite the breadth of skills required for success in this field, most biostatistics education programs place heavier emphasis on development of technical skills than skills necessary for collaborative work, including critical thinking, writing, and public speaking. Our master’s degree program in biostatistics aims for stronger integration of education in collaborative work alongside development of technical knowledge in biostatistics. Toward that end, we propose a model that provides students with a mental map for practicing biostatistics, and that can serve as a tool for faculty to create hands-on learning experiences for biostatistics students. The model helps students organize their knowledge of biostatistics, unifying the technical and collaborative aspects of the discipline in a single framework that can be applied across the broad array of activities that biostatisticians engage in. In this article we describe the model in detail and provide an initial assessment of whether the model might meet its intended purpose by applying the model to a common task for practicing biostatisticians and biostatistics students: describing the results of a medical research study.

Objective: In a Statistical Analysis System (SAS) coding interview, job applicants are typically presented with data management and data analysis problems and asked to solve them using the programming language of SAS. Interviewers not only assess technical competence, but also algorithm design and more generally how applicants approach computer programming. In the language of constructivism, the problems are designed to assess the depth and soundness of the applicant’s mental model of SAS programming. We asked whether a SAS course, embedded within a Master of Biostatistics program, could reasonably be structured using a coding interview for the final examination as its organizing framework. Methods: This is a case study, where we describe how our content delivery was structured in order to prepare students for their coding interviews. It additionally relies on the metaphor of learning a second language through immersion. Results: Using a constructivist approach enhanced with active learning exercises, a course could in fact be designed around a coding interview. Course content can be mapped to the metaphor of foreign language immersion. Student response has been positive, and the formative evaluation has been encouraging to date. Conclusions: Coding interviews are a novel and potentially promising way to design a course in SAS programming.

Background: African-Americans (AA) are 3 times more likely to have small-vessel-type ischemic strokes (SVS) than Whites. Small vessel strokes are associated with cognitive impairment, a relationship incompletely explained by white matter hyperintensity (WMH) burden. We examined whether inflammatory/endothelial dysfunction biomarkers are associated with cognition after SVS in AAs. Methods: Biomarkers were obtained in 24 subjects (median age 56.5 years, 54% women, median 12 years education). Cognition was assessed more than 6 weeks poststroke using the memory composite score (MCS), which was generated using recall from the Hopkins Verbal Learning Test-II and Brief Visuospatial Memory Test-Revised. A semi-automated, volumetric protocol was used to quantify WMH volume (WMHv) on clinical MRI scans. Potential biomarkers including vascular cell adhesion molecule-1 (VCAM-1), interleukin-1 receptor antagonist, interleukin-6, interleukin-8, interleukin-10, interferon gamma, and thrombin-antithrombin (TAT) were log-transformed and correlated with MCS with adjustment for potential confounders. Results: Among serum biomarkers, only VCAM-1-correlated with poorer memory based on the MCS (r = −.659; P = .0006). VCAM-1 (r = .554; P = .005) and age (r = .479; P = .018) correlated with WMHv; VCAM-1 was independently associated with MCS after adjustment for WMHv, age, and education (P = .023). Conclusions: The findings of this exploratory analysis suggest that endothelial dysfunction and inflammation as reflected by VCAM-1 levels may play a role in poststroke cognitive impairment. Additional studies are needed to validate this observation and to evaluate this relationship in non-AAs and with other stroke types and compare this finding to cognitive impairment in nonstroke populations.

Pruritus is a common symptom in cutaneous malignancies, but its impact on patients with solid tumors is unclear. We explored the impact and management of pruritus in patients with solid tumors, using patient-reported outcomes (PRO) data from a real-world registry.From 2006 to 2011, patients seen in the Duke Cancer Institute reported their symptoms via the Patient Care Monitor v2.0, a validated PRO tool that includes a 0-10-point question about pruritus severity. From 25,000 encounters, 203 patients reported severe pruritus ( 6/10) on at least one visit and 506 total visits were abstracted where patients reported either moderate or severe pruritus ( 3/10). From this cohort, we abstracted demographics, diagnosis, stage, cancer therapy, anti-pruritic therapy, and clinicians' responses.Mean age was 59.8 (SD 13.3), 134 (66%) were female, 125 (62%) were Caucasian, and 65 (32%) were African American. Breast cancer was the most common tumor (36.5%), followed by lung cancer (23.2%). Mean pruritus severity score was 6.8 (SD 1.8) for patients on chemotherapy, 6.9 (SD 1.8) for patients on targeted therapy alone or in combination, and 7.1(SD 1.8) for patients off treatment. Overall, 67% of patients reported at least two episodes of moderate-severe pruritus (mean # of visits 4.2 (SD 2.7)). Despite frequent report of severe and persistent pruritus, this was mentioned in just 28% of clinician notes and an intervention was recommended/prescribed in only 7% of visits.Pruritus is an under-addressed symptom in patients with solid tumors. Additional research is needed to understand the burden of pruritus in affected populations.

Background: Little is known about quality of life (QOL), depression, and end-of-life (EOL) outcomes among hospitalized patients with advanced cancer. Objective: To assess whether the surprise question identifies inpatients with advanced cancer likely to have unmet palliative care needs. Design: Prospective cohort study and long-term follow-up. Setting/Subjects: From 2008 to 2010, we enrolled 150 inpatients at Duke University with stage III/IV solid tumors or lymphoma/acute leukemia and whose physician would not be surprised if they died in less than one year. Measurements: We assessed QOL (FACT-G), mood (brief CES-D), and EOL outcomes. Results: Mean FACT-G score was quite low (66.9; SD 11). Forty-five patients (30%) had a brief CES-D score of ≥4 indicating a high likelihood of depression. In multivariate analyses, better QOL was associated with less depression (OR 0.91, p

The incidence of small vessel-type (lacunar) ischemic strokes is greater in African-Americans compared to whites. The chronic inflammatory changes that result from lacunar stroke are poorly understood. To elucidate these changes, we measured serum inflammatory and thrombotic biomarkers in African-Americans at least 6 weeks post-stroke compared to control individuals. Cases were African-Americans with lacunar stroke (n = 30), and controls were age-matched African-Americans with no history of stroke or other major neurologic disease (n = 37). Blood was obtained >6 weeks post-stroke and was analyzed for inflammatory biomarkers. Freshly isolated peripheral blood mononuclear cells were stimulated with lipopolysaccharide (LPS) to assess immune responsiveness in a subset of cases (n = 5) and controls (n = 4). After adjustment for covariates, the pro-inflammatory biomarkers, soluble vascular cadherin adhesion molecule-1 (sVCAM-1) and thrombin anti-thrombin (TAT), were independently associated with lacunar stroke. Immune responsiveness to LPS challenge was abnormal in cases compared to controls. African-Americans with lacunar stroke had elevated blood levels of VCAM-1 and TAT and an abnormal response to acute immune challenge >6 weeks post-stroke, suggesting a chronically compromised systemic inflammatory response.

Patients with advanced non-small cell lung cancer (aNSCLC) face a significant symptom burden. Little is known about the frequency and severity of symptoms over time, so we longitudinally characterized patients’ symptoms using the Patient Care Monitor (PCM) version 2.0, an electronic symptom-assessment tool. Ninety-seven patients with aNSCLC completed the PCM at up to four clinic visits. We analyzed symptom data by incidence, severity, type (functional vs. nonfunctional), proximity to death, and cancer anorexia-cachexia syndrome status (CACS). Functional concerns predominated, even in the non-CACS group. Average severity among the top 5 symptoms was worse for functional than nonfunctional items (mean difference 0.62, 95 % CI 0.22–1.01, P = 0.003). Severe dyspnea and fatigue were the most prevalent nonfunctional symptoms; moderate/severe dyspnea was reported by at least 29 % of patients, and fatigue by over 50 %. Depression was reported infrequently, with over half of patients at each visit reporting “none”; moderate or severe depression was reported in only 2.5–9.3 and 3.4–6.2 % of patients, respectively. The average number of moderate/severe symptoms increased with proximity to death; 84 % reported moderate/severe fatigue in the last 3 months of life, compared to 48 % at ≥12 months from death (P = 0.007). Patients with aNSCLC face a significant symptom burden, which increases with proximity to death. Symptom type and severity vary by proximity to death, but even patients without overt CACS report significant functional symptoms throughout. We recommend an individualized approach to palliative symptom intervention in advanced lung cancer, based on detailed symptom assessment and tracking.

Patient-reported outcome (PRO) measures, such as quality of life, have been associated with relevant clinical end points and are prognostic for survival outcomes in a variety of solid cancers in adults. In the past few years, PROs have garnered a greater influence as established and clinically relevant measures that could alter the current paradigm of practice-changing therapeutic advances, as it has been recognized that classic clinical end points do not accurately portray a full appreciation of the benefits, risks and costs of therapy. In this Review, we comprehensively assess the correlation of PROs with treatment response and survival, and explore tumour-related and patient-centric composite end points in patients with cancer participating in clinical trials. Comparisons or composite end points that consider tumour-related and PRO components might help health-care providers, patients with cancer and decision makers to better understand the total clinical benefit of therapeutic interventions.

Predictive models are increasingly being used in clinical practice. The aim of the study was to develop a predictive model to identify patients with platinum-resistant ovarian cancer with a prognosis of less than 6 to 12 months who may benefit from immediate referral to hospice care.A retrospective chart review identified patients with platinum-resistant epithelial ovarian cancer who were treated at our institution between 2000 and 2011. A predictive model for survival was constructed based on the time from development of platinum resistance to death. Multivariate logistic regression modeling was used to identify significant survival predictors and to develop a predictive model. The following variables were included: time from diagnosis to platinum resistance, initial stage, debulking status, number of relapses, comorbidity score, albumin, hemoglobin, CA-125 levels, liver/lung metastasis, and the presence of a significant clinical event (SCE). An SCE was defined as a malignant bowel obstruction, pleural effusion, or ascites occurring on or before the diagnosis of platinum resistance.One hundred sixty-four patients met inclusion criteria. In the regression analysis, only an SCE and the presence of liver or lung metastasis were associated with poorer short-term survival (P0.001). Nine percent of patients with an SCE or liver or lung metastasis survived 6 months or greater and 0% survived 12 months or greater, compared with 85% and 67% of patients without an SCE or liver or lung metastasis, respectively.Patients with platinum-resistant ovarian cancer who have experienced an SCE or liver or lung metastasis have a high risk of death within 6 months and should be considered for immediate referral to hospice care.

Objective Pillars4Life is an educational program that teaches coping skills to cancer patients in a virtual group setting; it was recently implemented at 17 hospitals across the USA. The cost-effective, scalable, and assessable Pillars4Life curriculum targets psychosocial resources (e.g., self-efficacy and coping skills) as a means to reduce symptoms (e.g., depression, anxiety, and posttraumatic stress) and enhance quality of life. Methods Cancer patients were recruited from hospitals that received the LIVESTRONG Community Impact Project Award to enroll in a pilot study of Pillars4Life. Consenting participants met with a certified instructor weekly for 10 weeks in a virtual environment; the manualized intervention trained participants in personal coping skills. Longitudinal assessments over 6 months were assessed using validated instruments to determine changes in Pillars4Life targeted resources and outcomes. Multiple linear regression models examined the relationship between changes in targeted resources and changes in outcome from baseline to 3 months post-intervention. Results Participants (n = 130) had the following characteristics: mean age of 56 ± 11 years, 87% women, 11% non-Caucasian, and 77% with college degree. At 3- and 6-month follow-up, mean scores improved on all key outcome measures such as depression (Patient Health Questionnaire), anxiety (Generalized Anxiety Disorder), posttraumatic stress (Posttraumatic Stress Disorder Checklist), fatigue (Functional Assessment of Chronic Illness Therapy—Fatigue), and well-being (Functional Assessment of Cancer Therapy—General) from baseline (all p

In a widely cited article, Ioannidis argued that most published research findings are false; particularly discovery research involving massive testing, genomics being a typical example. However, his argument ignores adjustment for multiple testing and thus should be taken with a large grain of salt. This is a potential example for statistics courses that concentrate on problem formulation.

Shared decision-making in acute myeloid leukemia (AML) requires understanding patients’ longitudinal experiences of illness, but little is known about the impact of remission status on patient-reported outcomes (PROs). We aimed to explore the association between remission status and PROs 6–12 months following induction chemotherapy. Forty-two patients completed three validated instruments characterizing symptom burden (Patient Care Monitor v2.0), distress (NCCN Distress Thermometer), and QOL (FACT-Leu), as part of a longitudinal observational study. We used regression models to explore the relationship between remission status and PROs, and explore differences by initial disease type (de novo versus secondary/relapsed AML). Those with secondary or relapsed AML at study onset had marked impairments in all measures compared to de novo AML patients. After 6 months, their mean distress score was 4.8 (> 4.0 warrants intervention), they reported a mean of 14.1 moderate/severe symptoms and had a mean QOL score of 113.6, compared to 1.0, 1.7, and 155.2, respectively, for those with de novo AML (p

This non-technical tutorial focus on two questions about the analysis of data from randomised trials. Which is the more appropriate analysis of data from a randomised trial – an unadjusted analysis or an adjusted one? When a result is not statistically significant is it nevertheless appropriate to comment on its direction?

BACKGROUND Pain is a challenge for patients following hematopoietic stem cell transplantation (HCT). OBJECTIVE This study aimed to develop and test the feasibility, acceptability, and initial efficacy of a Web-based mobile pain coping skills training (mPCST) protocol designed to address the needs of HCT patients. METHODS Participants had undergone HCT and reported pain following transplant (N=68). To guide intervention development, qualitative data were collected from focus group participants (n=25) and participants who completed user testing (n=7). After their input was integrated into the mPCST intervention, a pilot randomized controlled trial (RCT, n=36) was conducted to examine the feasibility, acceptability, and initial efficacy of the intervention. Measures of acceptability, pain severity, pain disability, pain self-efficacy, fatigue, and physical disability (self-report and 2-min walk test [2MWT]) were collected. RESULTS Participants in the focus groups and user testing provided qualitative data that were used to iteratively refine the mPCST protocol. Focus group qualitative data included participants’ experiences with pain following transplant, perspectives on ways to cope with pain, and suggestions for pain management for other HCT patients. User testing participants provided feedback on the HCT protocol and information on the use of videoconferencing. The final version of the mPCST intervention was designed to bridge the intensive outpatient (1 in-person session) and home settings (5 videoconferencing sessions). A key component of the intervention was a website that provided personalized messages based on daily assessments of pain and activity. The website also provided intervention materials (ie, electronic handouts, short videos, and audio files). The intervention content included pain coping advice from other transplant patients and instructions on how to apply pain coping skills while engaging in meaningful and leisure activities. In the RCT phase of this research, HCT patients (n=36) were randomized to receive the mPCST intervention or to proceed with the treatment as usual. Results revealed that the mPCST participants completed an average of 5 out of 6 sessions. The participants reported that the intervention was highly acceptable (mean 3/4), and they found the sessions to be helpful (mean 8/10) and easy to understand (mean 7/7). The mPCST participants demonstrated significant improvements in pre- to post-treatment pain, self-efficacy (P=.03, d=0.61), and on the 2MWT (P=.03, d=0.66), whereas the patients in the treatment-as-usual group did not report any such improvements. Significant changes in pain disability and fatigue were found in both groups (multiple P CONCLUSIONS Using focus groups and user testing, we developed an mPCST protocol that was feasible, acceptable, and beneficial for HCT patients with pain. CLINICALTRIAL ClinicalTrials.gov NCT01984671; https://clinicaltrials.gov/ct2/show/NCT01984671 (Archived by WebCite at http://www.webcitation.org/6xbpx3clZ)

Background. Health care-related costs and satisfaction are compelling targets for quality improvement in cancer care delivery; however, little is known about how financial burden affects patient satisfaction. Methods. This was an observational, cross-sectional, survey-based study assessing patient-reported financial burden (FB). Eligible patients were ≥21 years with solid tumor malignancy and were receiving chemotherapy or hormonal therapy for ≥1 month. The Patient Satisfaction Questionnaire Short-Form assessed patient satisfaction with health care. Subjective FB related to cancer treatment was measured on a 5-point Likert scale. Results. Of 174 participants (32% response rate), 47% reported significant/catastrophic FB. Participants reported highest satisfaction with interpersonal manner and lowest satisfaction with financial aspects of care. In adjusted analysis, high FB was negatively associated with general satisfaction (coefficient: −.29), satisfaction with technical quality (coefficient: −.26), and satisfaction with financial aspects of care (coefficient: −.62). Older age was associated with higher scores in all satisfaction subscales except patient-physician communication and financial aspects. Annual household income of Conclusion. FB is a potentially modifiable correlate of poor satisfaction with cancer care including general satisfaction and satisfaction with the technical quality of care. Addressing cancer-associated FB may lead to improved satisfaction, which in turn can influence adherence, outcomes, and quality of life.

The authors found that cost-related medication nonadherence was prevalent among patients with cancer who sought financial assistance.

Background Efficient dietary interventions for patients with hypertension in clinical settings are needed. Objective To assess the separate and combined influence of a physician intervention (MD-I) and a patient intervention (PT-I) on dietary intakes of patients with hypertension. Design A nested 2×2 design, randomized controlled trial conducted over 18 months. Participants A total of 32 physicians and 574 outpatients with hypertension. Intervention MD-I included training modules addressing the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure hypertension management guidelines and lifestyle modification. PT-I included lifestyle coaching to adopt the Dietary Approaches to Stop Hypertension (DASH) eating pattern, reduce sodium intake, manage weight, increase exercise, and moderate alcohol intake. Main outcome measures Dietary intakes were measured by the Block Food Frequency Questionnaire. Concordance with the DASH dietary pattern was estimated by a DASH score. Statistical analyses The main effects of MD-I and PT-I, and their interaction, were evaluated using analysis of covariance. Results After 6 months of intervention, MD-I participants significantly increased intakes of potassium, fruits, juices, and carbohydrate; decreased intake of fat; and improved overall dietary quality as measured by the Healthy Eating Index. PT-I intervention resulted in increased intakes of carbohydrate, protein, fiber, calcium, potassium, fruits and fruit juices, vegetables, dairy and Healthy Eating Index score, and decreased intakes in fat, saturated fat, cholesterol, sodium, sweets, and added fats/oils/sweets. In addition, PT-I improved overall DASH concordance score. The change in DASH score was significantly associated with the changes in blood pressure and weight at 6 months. At 18 months, most changes reversed back toward baseline levels, including the DASH score. Conclusions Both MD-I and PT-I improved eating patterns at 6 months with some sustained effects at 18 months. Even though all dietary changes observed were consistent with the DASH nutrient targets or food group guidelines, only the PT-I intervention was effective in improving the overall DASH concordance score. This finding affirms the role of medical nutrition therapy in long-term intensive interventions for hypertension risk reduction and weight management and underlines the need for development of maintenance strategies. Furthermore, this study emphasizes the importance of collaborations among physicians, registered dietitians and other dietetics practitioners, and lay health advisors while assisting patients to make healthy behavior changes.

Objective: To investigate sexual orientation differences in college men's motivations for HIV testing. Participants: 665 male college students in the Southeastern United States from 2006 to 2014. Methods: Students completed a survey on HIV risk factors and testing motivations. Logistic regressions were conducted to determine the differences between heterosexual men (HM) and sexual minority men (SMM). Results: SMM were more motivated to get tested by concern over past condomless sex, while HM were more often cited supporting the testing program “on principle” and wanting a free t-shirt. SMM and HM differed in behaviors that impact HIV risk and other demographics. However, differences in testing motivation by concern over past condomless sex or wanting a free t-shirt persisted when controlling for these demographic and behavioral differences. Conclusions: Appropriately designed HIV prevention interventions on college campuses should target SMM's distinct concern over past condomless sex as a testing...

Context: In the emerging Learning Health System (LHS), the application and generation of medical knowledge are a natural outgrowth of patient care. Achieving this ideal requires a physician workforce adept in information systems, quality improvement methods, and systems-based practice to be able to use existing data to inform future care. These skills are not currently taught in medical school or graduate medical education.Case Description: We initiated a first-ever Learning Health Systems Training Program (LHSTP) for resident physicians. The curriculum builds analytical, informatics and systems engineering skills through an active-learning project utilizing health system data that culminates in a final presentation to health system leadership.Findings: LHSTP has been in place for two years, with 14 participants from multiple medical disciplines. Challenges included scheduling, mentoring, data standardization, and iterative optimization of the curriculum for real-time instruction. Satisfaction surveys and feedback were solicited mid-year in year 2. Most respondents were satisfied with the program, and several participants wished to continue in the program in various capacities after their official completion.Major themes: We adapted our curriculum to successes and challenges encountered in the first two years. Modifications include a revised approach to teaching statistics, smaller cohorts, and more intensive mentorship. We continue to explore ways for our graduates to remain involved in the LHSTP and to disseminate this program to other institutions.Conclusion: The LHSTP is a novel curriculum that trains physicians to lead towards the LHS. Successful methods have included diverse multidisciplinary educators, just in time instruction, tailored content, and mentored projects with local health system impact.

Patterns of medical resource use near the end of life may differ across modes of death. The aim of this study was to characterize patterns of inpatient resource use and direct costs for patients with heart failure (HF) who died of sudden cardiac death (SCD), HF, other cardiovascular causes, or noncardiovascular causes during the last year of life. Data were from a randomized trial of exercise training in patients with HF. Mode of death was adjudicated by an end point committee. Generalized estimating equations were used to compare hospitalizations, inpatient days, and inpatient costs incurred during the final year of life in patients who died of different causes, adjusting for clinical and treatment characteristics. Of 2,331 patients enrolled in the trial, 231 died after ≥1 year of follow-up with an adjudicated mode of death, including 72 of SCD, 80 of HF, 34 of other cardiovascular causes, and 45 of noncardiovascular causes. Patients who died of SCD were younger, had less severe HF, and incurred fewer hospitalizations, fewer inpatient days, and lower inpatient costs than patients who died of other causes. After adjustment for patient characteristics, inpatient resource use varied by 2 to 4 times across modes of death, suggesting that cost-effectiveness analyses of interventions that reduce mortality from SCD compared to other causes should incorporate mode-specific end-of-life costs. In conclusion, resource use and associated medical costs in the last year of life differed markedly in patients with HF who experienced SCD and patients who died of other causes.

Background The standard clinical approach for reducing cardiovascular disease risk due to dyslipidemia is to prescribe changes in diet and physical activity. The purpose of the current study was to determine if, across a range of dietary patterns, there were variable lipoprotein responses to an aerobic exercise training intervention. Methods Subjects were participants in the STRRIDE I, a supervised exercise program in sedentary, overweight subjects randomized to 6 months of inactivity or 1 of 3 aerobic exercise programs. To characterize diet patterns observed during the study, we calculated a modified z-score that included intakes of total fat, saturated fat, trans fatty acids, cholesterol, omega-3 fatty acids, and fiber as compared with the 2006 American Heart Association diet recommendations. Linear models were used to evaluate relationships between diet patterns and exercise effects on lipoproteins/lipids. Results Independent of diet, exercise had beneficial effects on low-density lipoprotein cholesterol particle number, lowdensity lipoprotein cholesterol size, high-density lipoprotein cholesterol, high-density lipoprotein cholesterol size, and triglycerides (P b .05 for all). However, having a diet pattern that closely adhered to American Heart Association recommendations was not related to changes in these or any other serum lipids or lipoproteins in any of the exercise groups. Conclusions We found that even in sedentary individuals whose habitual diets vary in the extent of adherence to AHA dietary recommendations, a rigorous, supervised exercise intervention can achieve significant beneficial lipid effects. (Am Heart J 2012;164:117-24.)

While the benefits of exercise are clear, many unresolved issues surround the optimal exercise prescription. Many organizations recommend aerobic training (AT) and resistance training (RT), yet few studies have compared their effects alone or in combination. The purpose of this study, part of Studies Targeting Risk Reduction Interventions Through Defined Exercise-Aerobic Training and/or Resistance Training (STRRIDE/AT/RT), was to compare the effects of AT, RT, and the full combination (AT/RT) on central ectopic fat, liver enzymes, and fasting insulin resistance [homeostatic model assessment (HOMA)]. In a randomized trial, 249 subjects [18–70 yr old, overweight, sedentary, with moderate dyslipidemia (LDL cholesterol 130–190 mg/dl or HDL cholesterol ≤40 mg/dl for men or ≤45 mg/dl for women)] performed an initial 4-mo run-in period. Of these, 196 finished the run-in and were randomized into one of the following 8-mo exercise-training groups: 1) RT, which comprised 3 days/wk, 8 exercises, 3 sets/exercise, 8–12 repetitions/set, 2) AT, which was equivalent to ∼19.2 km/wk (12 miles/wk) at 75% peak O2 uptake, and 3) full AT + full RT (AT/RT), with 155 subjects completing the intervention. The primary outcome variables were as follows: visceral and liver fat via CT, plasma liver enzymes, and HOMA. AT led to significant reductions in liver fat, visceral fat, alanine aminotransferase, HOMA, and total and subcutaneous abdominal fat (all P < 0.05). RT resulted in a decrease in subcutaneous abdominal fat ( P < 0.05) but did not significantly improve the other variables. AT was more effective than RT at improving visceral fat, liver-to-spleen ratio, and total abdominal fat (all P < 0.05) and trended toward a greater reduction in liver fat score ( P < 0.10). The effects of AT/RT were statistically indistinguishable from the effects of AT. These data show that, for overweight and obese individuals who want to reduce measures of visceral fat and fatty liver infiltration and improve HOMA and alanine aminotransferase, a moderate amount of aerobic exercise is the most time-efficient and effective exercise mode.

Performance status is prognostic in oncology and palliative care settings. Traditionally clinician rated, it is often inconsistently collected, recorded, and measured, thereby limiting its utility. Patient-reported strategies are increasingly used for routine symptom and quality of life assessment in the clinic, and may be useful for tracking performance status.Tablet personal computers were used to collect patient-reported reviews of systems via the Patient Care Monitor (PCM) v2.0 for 86 patients with advanced lung cancer. Relevant subscales included the PCM Impaired Performance and Impaired Ambulation scales. Trained nurse clinicians measured performance status using traditional Karnofsky and Eastern Cooperative Oncology Group (ECOG) instruments. Correlation coefficients were used to compare performance status scales, and survival analysis was performed by Cox proportional hazards modeling.All four performance status scales demonstrated excellent internal consistency and convergent validity. Initial KPS and ECOG scores were statistically correlated with survival, whereas PCM scores showed a nonsignificant trend in this direction. Change in PCM Impaired Performance over time was statistically correlated with survival (hazard ratio = 1.62, P = .046), whereas the other three performance status measures were not statistically prognostic.Patient-reported performance status as measured by PCM v2.0 is at least as reliable as KPS or ECOG. The enhanced resolution provided by this patient-reported method allows for the detection of clinically meaningful changes in trajectory over time, potentially serving as an early-warning system to trigger clinical interventions. Further study is needed to test these findings on a larger scale.

ObjectivesTo determine utility scores for health states relevant to the treatment of early-stage, high-risk cervical cancer.MethodsSeven descriptive health states incorporating the physical and emotional aspects of medical treatment, recovery, and prognosis were developed. Forty-five female volunteers valuated each health state using the visual analogue score (VAS) and time trade off (TTO) methods. Treatment options were ranked by mean and median TTO scores. The 95% confidence intervals were calculated to determine the statistical significance of ranking preferences. The Wilcoxon rank-sum test was used to compare central tendencies related to age, race, parity, and subject history of abnormal cervical cytology.ResultsVAS and TTO scores were highly correlated. Volunteers ranked minimally invasive radical hysterectomy with low-risk features as most preferred (mean TTO = 0.96; median TTO = 1.00) and aborted radical hysterectomy followed by chemoradiation as least preferred (mean TTO = 0.69; median TTO = 0.83). Health states that included radical surgery were ranked higher than those that included chemoradiation, either in the adjuvant or primary setting. When survival was comparable, volunteers rated radical hysterectomy with high-risk pathology followed by adjuvant chemoradiation (mean TTO = 0.78; median TTO = 0.92; 95% CI: 0.69–0.87) similarly to chemoradiation alone (mean TTO = 0.76; median TTO 0.90; 95% CI: 0.66–0.86; p = NS). Utility scores for the majority of health states were not significantly associated with age, race, parity, or subject history of abnormal cervical cytology.ConclusionSubjects consistently preferred surgical excision to treat early-stage, high-risk cervical cancer and chose a minimally invasive approach. Such utility scores can be used to incorporate quality-of-life effects into comparative-effectiveness models for cervical cancer.

Objective.To identify patient-care practices related to an increased prevalence of hepatitis C virus (HCV) infection among chronic hemodialysis patients.Design.Survey.Setting.Chronic hemodialysis facilities in the United States.Participants.Equal-probability 2-stage cluster sampling was used to select 87 facilities from all Medicare-approved providers treating 30–150 patients; 53 facilities and 2,933 of 3,680 eligible patients agreed to participate.Methods.Patients were tested for HCV antibody and HCV RNA. Data on patient-care practices were collected using direct observation.Results.The overall prevalence of HCV infection was 9.9% (95% confidence interval [CI], 8.2%–11.6%); only 2 of 294 HCV-positive patients were detected solely by HCV RNA testing. After adjusting for non-dialysis-related HCV risk factors, patient-care practices independently associated with a higher prevalence of HCV infection included reusing priming receptacles without disinfection (odds ratio [OR], 2.3 [95% CI, 1.4–3.9]), handling blood specimens adjacent to medications and clean supplies (OR, 2.2 [95% CI, 1.3–3.6]), and using mobile carts to deliver injectable medications (OR, 1.7 [95% CI, 1.0–2.8]). Independently related facility covariates were at least 10% patient HCV infection prevalence (OR, 3.0 [95% CI, 1.8–5.2]), patient-to-staff ratio of at least 7: 1 (OR, 2.4 [95% CI, 1.4–4.1]), and treatment duration of at least 2 years (OR, 2.4 [95% CI, 1.3–4.4]).Conclusions.This study provides the first epidemiologic evidence of associations between specific patient-care practices and higher HCV infection prevalence among hemodialysis patients. Staff should review practices to ensure that hemodialysis-specific infection control practices are being implemented, especially handling clean and contaminated items in separate areas, reusing items only if disinfected, and prohibiting mobile medication and clean supply carts within treatment areas.

We searched MEDLINE, EMBASE and the Cochrane Controlled Trials Register to determine whether oxygen relieves dyspnoea in mildly or non-hypoxemic COPD and included 18 randomised controlled trials (431 participants) in the meta-analysis using Cochrane methodology. Oxygen therapy reduced dyspnoea when compared with medical air; standardised mean difference -0.37 (95% CI -0.50 to -0.24; I(2)=14%). In a priori subgroup and sensitivity analyses, dyspnoea was reduced by continuous oxygen during exertion but not short-burst oxygen therapy. Continuous exertional oxygen can relieve dyspnoea in mildly or non-hypoxemic COPD, but evidence from larger clinical trials is needed.

Importance Data from animal models show that the administration of dextroamphetamine combined with task-relevant training facilitates recovery after focal brain injury. Results of clinical trials in patients with stroke have been inconsistent. Objectives To collect data important for future studies evaluating the effect of dextroamphetamine combined with physiotherapy for improving poststroke motor recovery and to test the efficacy of the approach. Design, Setting, Participants This pilot, double-blind, block-randomized clinical trial included patients with cortical or subcortical ischemic stroke and moderate or severe motor deficits from 5 rehabilitation hospitals or units. Participants were screened and enrolled from March 2001 through March 2003. The primary outcome was assessed 3 months after stroke. Study analysis was completed December 31, 2015. A total of 1665 potential participants were screened and 64 were randomized. Participants had to begin treatment 10 to 30 days after ischemic stroke. Data analysis was based on intention to treat. Interventions Participants were allocated to a regimen of 10 mg of dextroamphetamine (n = 32) or placebo (n = 32) combined with a 1-hour physical therapy session beginning 1 hour after drug or placebo administration every 4 days for 6 sessions in addition to standard rehabilitation. Main Outcomes and Measures The primary outcome was the difference between groups in change in Fugl-Meyer motor scores from baseline to 3 months after stroke (intention to treat with dextroamphetamine). Secondary exploratory measures included the National Institutes of Health Stroke Scale, Canadian Neurological Scale, Action Research Arm Test, modified Rankin Scale score, Functional Independence Measure, Ambulation Speed and Distance, Mini-Mental State Examination, Beck Depression Inventory, and Stroke Impact Scale. Results Among the 64 patients randomized to dextroamphetamine vs placebo (55% men; median age, 66 years; age range, 27-91 years), no overall treatment-associated difference in the mean (SEM) change in Fugl-Meyer motor scores from baseline to 3 months after stroke was noted (−18.65 [2.27] points with dextroamphetamine vs −20.83 [2.94] points with placebo;P = .58). No overall treatment-associated differences in any of the study’s secondary measures and no differences in subgroups based on stroke location or baseline severity were found. No adverse events were attributed to study treatments. Conclusions and Relevance Treatment with dextroamphetamine combined with physical therapy did not improve recovery of motor function compared with placebo combined with physical therapy as assessed 3 months after hemispheric ischemic stroke. The studied treatment regimen was safe. Trial Registration ClinicalTrials.gov identifier:NCT01905371