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Objectives: To investigate the relationship between barometric pressure and the incidence of benign paroxysmal positional vertigo (BPPV)., Methods: 181 patients diagnosed with classic BPPV seen between 2011 and 2016 were identified. Demographic information, data of onset, and date of presentation were recorded. Historical barometric data for each of the 60 months were recorded. In addition, monthly counts of other atmospheric, infectious, and allergic variables for that time period were recorded. Correlation analysis compared monthly incidence of BPPV with absolute and relative changes in atmospheric conditions., Results: The incidence of BPPV onset demonstrated a statistically significant positive correlation with barometric pressure, where every one-unit increase in barometric pressure leads to an expected increase of 6.1 diagnoses (p = 0.0008). The correlation coefficient (r) between barometric pressure and BPPV diagnoses was 0.66 (95% CI 0.14-0.90) with a p-value of 0.0131. Other seasonal variables demonstrated correlation, though none as strong as barometric pressure., Conclusions: Barometric pressure has been long been associated with conditions of the inner ear, though its relationship to the pathogenesis of BPPV has not been investigated. Monthly changes in barometric pressure, rather than the absolute value, may be responsible for the observed changes in incidence. These findings demonstrate a clear association between barometric pressure and BPPV that may help to explain both the etiology of BPPV and its possible connection to migraine-related conditions., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Although Web-based questionnaires are an efficient, increasingly popular mode of data collection, their utility is often challenged by high participant dropout. Researchers can gain insight into potential causes of high participant dropout by analyzing the dropout patterns., Objective: This study proposed the application of and assessed the use of user-specified and existing hypothesis testing methods in a novel setting-survey dropout data-to identify phases of higher or lower survey dropout., Methods: First, we proposed the application of user-specified thresholds to identify abrupt differences in the dropout rate. Second, we proposed the application of 2 existing hypothesis testing methods to detect significant differences in participant dropout. We assessed these methods through a simulation study and through application to a case study, featuring a questionnaire addressing decision-making surrounding cancer screening., Results: The user-specified method set to a low threshold performed best at accurately detecting phases of high attrition in both the simulation study and test case application, although all proposed methods were too sensitive., Conclusions: The user-specified method set to a low threshold correctly identified the attrition phases. Hypothesis testing methods, although sensitive at times, were unable to accurately identify the attrition phases. These results strengthen the case for further development of and research surrounding the science of attrition., (©Camille J Hochheimer, Roy T Sabo, Robert A Perera, Nitai Mukhopadhyay, Alex H Krist. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 23.08.2019.)

Objective: Over the two years following the 2012 introduction of CMS's National Partnership, combined rates of schizophrenia, Tourette's, and Huntington's in US long-stay residents increased 12%. We evaluated trends in reporting of these diagnoses for the subgroup of long-stay residents on antipsychotics., Methods: Retrospective analysis of Virginia Medicaid claims identified annual utilization rates of psychiatric diagnoses for long-stay seniors on antipsychotics. Chi-square analysis compared rates for the year before March, 2012 with the same 12-month period 1 year later. A 5-year pre-existing baseline rate was also obtained., Results: Diagnosis rates for 2011 were unchanged from baseline. Comparing 2011 with 2013, diagnoses rates for schizophrenia, Tourette's, and Huntington's combined increased 40% (p < .0001), primarily because schizophrenia reporting nearly doubled (p < .0001)., Conclusions: For long-stay seniors on antipsychotics, reporting of schizophrenia, Tourette's, and Huntington's began increasing in 2012 and at almost triple the rate CMS described for the general long-stay population. The increased reporting of these diagnoses described by CMS since 2012 appears to be new and concentrated in residents on antipsychotics Clinical Implications: Since antipsychotics prescribed for schizophrenia, Tourette's, and Huntington's are excluded from quality-measure auditing, apparent reductions in inappropriate long-stay antipsychotic use since the National Partnership may be exaggerated.

Background: Primary care clinicians write 45% of all opioid prescriptions in the United States, but little is known about the characteristics of patients who receive them and the clinicians who prescribe opioids in primary care settings. Our study aimed to describe the patient and clinician characteristics and clinicians' perspectives of chronic opioid prescribing in primary care., Methods: Using a mixed methods approach, we completed an analysis of 2016 electronic health records from 21 primary care practices to identify patients who had received chronic opioids, which we defined as in receipt of an opioid prescription for at least 3 consecutive months. We compared those receiving chronic opioids with those not in terms of their demographics, prescribing clinician characteristics, and risk factors for opioid-related harms, as identified by the Centers for Disease Control and Prevention Guideline on Opioid Prescribing for Chronic Pain. We then interviewed 16 primary care clinicians about their perspectives on chronic opioid prescribing., Results: Of 84,029 patients, 1.1% (902/84,929) received chronic opioid prescriptions. Characteristics associated with being prescribed chronic opioids include being female, being of black or African American race, and having risks for opioid-related harms, such as mental health diagnoses, substance use disorder, and concurrent benzodiazepine use. Clinicians report multiple difficulties in weaning patients from chronic opioids, including medical contraindications of nonopioid alternatives and difficulty justifying weaning by stable long-term patients., Conclusion: Although patients prescribed opioids in primary care have higher risks of opioid-related harms, clinicians report multiple barriers in deprescribing chronic opioids. Future studies should examine strategies to mitigate these harms and engage patients in shared decision making about their chronic opioid use., (© 2019 Annals of Family Medicine, Inc.)

Loneliness is associated with poor health outcomes, and there is growing attention on loneliness as a social determinant of health. Our study sought to determine the associations between community factors and loneliness. The Three-Item Loneliness Scale and zip codes of residence were collected in primary care practices in Colorado and Virginia. Living in zip codes with higher unemployment, poor access to health care, lower income, higher proportions of blacks, and poor transportation was associated with higher mean loneliness scores. Future studies that examine interventions addressing loneliness may be more effective if they consider social context and community characteristics., (© 2019 Annals of Family Medicine, Inc.)

Purpose: Loneliness has important health consequences. Little is known, however, about loneliness in primary care patient populations. This study describes the prevalence of loneliness in patients presenting for primary care and associations with self-reported demographic factors, health care utilization, and health-related quality of life., Methods: We conducted cross-sectional surveys of adults presenting for routine care to outpatient primary care practices in 2 diverse practice-based research networks. The 3-item University of California, Los Angeles Loneliness Scale was utilized to determine loneliness., Results: The prevalence of loneliness was 20% (246/1,235). Loneliness prevalence was inversely associated with age ( P <.01) and less likely in those who were married ( P <.01) or employed ( P <.01). Loneliness was more common in those with lower health status ( P <.01), including when adjusting for employment and relationship status (odds ratio [OR] = 1.05; 95% CI, 1.03-1.07). Primary care visits (OR = 1.07; 95% CI, 1.03-1.10), urgent care/emergency department visits (OR = 1.24; 95% CI, 1.12-1.38), and hospitalizations (OR = 1.15; 95% CI, 1.01-1.31) were associated with loneliness status. There was no significant difference in rates of loneliness between sexes ( P = .08), racial categories ( P = .57), or rural and urban respondents ( P = .42)., Conclusions: Our findings demonstrate that loneliness is common in primary care patients and is associated with adverse health consequences including poorer health status and greater health care utilization. Further work is needed to understand the value of screening for and using interventions to treat loneliness in primary care., (© 2019 Annals of Family Medicine, Inc.)

Lymphoid recovery following myeloablative stem cell transplantation (SCT) displays a logistic pattern of exponential growth followed by a plateau. Within this logistic framework, lymphoid recovery is characterized by the parameters R (slope of ascent), a (time of maximal rate of ascent) and K (plateau), the 'steady-state' lymphocyte count. A retrospective analysis of allogeneic SCT performed from 2008 to 2013 was undertaken to compare lymphoid recovery and clinical outcomes in 131 patients with acute myelogenous leukemia, acute lymphocytic leukemia, and myelodysplastic syndromes. Using Prism software, a logistic curve was successfully fit to the absolute lymphocyte count recovery in all patients. Patients were classified according to the magnitude and rate of lymphoid recovery; pattern A achieved an absolute lymphocyte counts (ALC) of >1000/μL by day 45, pattern B an ALC 500 < x < 1000/μL, and pattern C an ALC <500/μL. Pattern A was characterized by a higher mean K (p < .0001) compared with patterns B and C. Patients with patterns B and C were more likely to have mixed T cell chimerism at 90 d following SCT (p = .01). There was a trend towards improved survival (and relapse-free survival) in those with pattern A and B at 1 year compared to pattern C (p = .073). There was no difference in cGVHD (p = .42) or relapse (p = .45) between pattern types. Cytomegalovirus (CMV), aGVHD, and all relapse were heralded by deviation from logistic behavior. Pattern C patients were more likely to require donor lymphocyte infusion (DLI) (p = .017). Weaning of tacrolimus post-transplant was associated with a second, separate logistic expansion in some patients. This study demonstrated that lymphoid reconstitution follows a prototypical logistic recovery and that pattern observed correlates with T cell chimerism and need for DLI, and may influence survival.

Allogeneic hematopoietic cell transplantation (HCT) is a curative option for patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), but carries a high risk of relapse. This retrospective review evaluates the effectiveness of maintenance azacitidine in high-risk AML and MDS patients to reduce the probability of relapse. Twenty-five patients who received maintenance azacitidine were matched to historical controls in a two-to-one ratio based on diagnosis, donor type, conditioning regimen intensity, and age. Over 90% of patients received myeloablative conditioning. There was no difference in time to hematologic relapse, overall survival, or non-relapse mortality. Maintenance therapy was stopped early in 72% of patients due to graft-versus-host-disease, relapse, infection, and intolerance (13 of 25 patients received less than 4 cycles). There was a trend towards higher toxicity in the azacitidine group. The use of prophylactic azacitidine following myeloablative allogeneic HCT outside a clinical trial cannot be recommended at this time.

Background and Objectives: It is unclear which specific well-child visits (WCVs) are most frequently missed and whether age-specific patterns of attendance differ by race or insurance type., Methods: We conducted a retrospective cohort study of children 0 to 6 years old between 2011 and 2016 within 2 health networks spanning 20 states. WCVs were identified by using International Classification of Diseases, Ninth and 10th Revisions and Current Procedural Terminology codes. We calculated adherence to the 13 American Academy of Pediatrics-recommended WCVs from birth to age 6 years. To address data completeness, we made 2 adherence calculations after a child's last recorded WCV: 1 in which we assumed all subsequent WCVs were attended outside the network and 1 in which we assumed none were., Results: We included 152 418 children in our analysis. Most children were either publicly insured (77%) or uninsured (14%). The 2-, 4-, and 6-month visits were the most frequently attended (63% [assuming no outside care after the last recorded WCV] to 90% [assuming outside care]), whereas the 15- and 18-months visits (41%-75%) and 4-year visit (19%-49%) were the least frequently attended. Patients who were publicly insured and uninsured (versus privately insured) had higher odds of missing WCVs. Hispanic and Asian American (versus non-Hispanic white) patients had higher odds of attending WCVs., Discussion: The 15- and 18-month WCVs as well as the 4-year WCV are the least frequently attended WCVs. The former represent opportunities to identify developmental delays, and the latter represents an opportunity to assess school readiness., Competing Interests: POTENTIAL CONFLICT OF INTEREST: Dr Krist is a member of the US Preventive Services Task Force, but this article does not necessarily represent the views and policies of the US Preventive Services Task Force; the other authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2018 by the American Academy of Pediatrics.)

In this study, we used a rapid, highly-sensitive, single-cell biomass measurement method, Live Cell Interferometry (LCI), to measure biomass in populations of CD3 + T cells isolated from hematopoietic stem cell transplant (SCT) patients at various times pre- and post-transplant (days 0-100). CD3 + T cell 'mass spectra' were obtained from five autologous and 20 allogenic transplant recipients. We found a pronounced rise in median T cell biomass (+25%; p <0.001) shortly after transplant (day 14), which moderated by day 60. Further, the inter-patient and intra-patient cell masses were most variable at days 14 and 30 post-transplant. T cell biomass trends were similar in both autologous and allogenic transplant recipients. These data suggest that T cell biomass changes are associated with immune reconstitution occurring in the first few weeks post-transplant. To our knowledge, this is the first time single-cell biomass measurements have been studied in human clinical trials. With refinement, these data may prove useful in guiding the withdrawal of immunosuppression following SCT, reducing the likelihood of Graft-Versus-Host Disease or cancer relapse occurring.

Purpose: The shift from infusion to oral oncolytic therapy presents challenges to oncology practitioners. The purpose of this study was to describe how a statewide quality-improvement collaborative can enhance quality of care for patients receiving oral oncolytic therapy., Methods: The Michigan Oncology Quality Consortium hosted a series of learning sessions focused on oral oncolytic quality improvement, providing multiple resources to oncology community practices. The first five participating practices reported which of the evidence-based Michigan Oncology Quality Consortium resources provided were implemented at their site. They also performed prepost self-assessments in October 2013 and April 2015 and another in December 2017 to assess sustainability. Concordance with the ASCO Quality Oncology Practice Initiative oral chemotherapy standards, including documentation (five measures), patient education (seven measures), and follow-up/monitoring (four measures), was compared., Results: All practices showed improvement between 2013 and 2015 in documentation (32% to 88%; P = .03), patient education (37% to 100%; P could not be calculated), and monitoring (40% to 80%; P > .2). Overall, a significant improvement in concordance was observed (36% to 91%; P = .03). Use of resources from each practice varied, and practices that used more resources showed greater improvements. There was a slight decrease in overall concordance between 2015 and 2017, which was not found to be significant (91% to 84%; P = .53)., Conclusion: Use of tools from a quality-improvement collaborative improved concordance with national standards of care. Large-scale deployment of this model program may provide a clinically efficient and effective mechanism to enhance widespread change.

Purpose: To accurately measure external auditory canal (EAC) dimensions by high resolution computed tomography (CT), and compare results with a traditional method of EAC measurement., Methods: Using an advanced multidimensional open source digital imaging and communications in medicine (DICOM) analysis program (OsiriX, Pixmeo, Geneva, Switzerland) 91 adult EACs were analyzed on a previously obtained temporal bone CT scan. Tympanometric data were also recorded for each ear. The methods were compared using a linear mixed effect model., Results: EAC volume was compared between tympanometrically calculated volumes and CT measured volumes. It was found that CT measured volumes are, on average, smaller (1.12cm 3 , SE=0.04) than tympanometry volumes (1.27cm 3 , SE=0.04cm 3 ). There was a significant difference in CT measured volume between genders (p=0.0125), with males having larger measured volumes (1.23cm 3 , SD=0.28cm 3 ) than females (1.06cm 3 , SD=0.20cm 3 ). There was a significant difference in average circumference between ear laterality (p=0.0071), with the right ear having a slightly larger average circumference (2.49cm, SD=0.23cm) than the left ear (2.44cm, SD=0.50cm).There was also a significant difference in minimum circumference between age groups (p=0.0448), with patients younger than 60years having larger minimum circumferences (1.89cm, SD=0.21cm) than older patients (1.78cm, SD=0.25cm)., Conclusions: This study demonstrates that CT analysis can provide more information about EAC dimensions than traditional techniques. Moreover, slight but statistically significant differences are associated with age, gender and laterality. Accurate estimation of EAC dimensions is important for the development of hearing aids and personal protective equipment and can also be helpful for surgical planning, specifically otoendoscopy. Future research will focus on simplifying computation, developing cross-cultural cohort comparisons, and application to otoendoscopic procedures., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Introduction: Engaging patients to make informed choices is paramount but difficult in busy practices. This study sought to engage patients outside the clinical setting to better understand how they approach cancer screening decisions, including their primary concerns and their preferences for finalizing their decision., Methods: Twelve primary care practices offering patients an online personal health record invited eligible patients to complete a 17-item online interactive module. Among 11,458 registered users, invitations to complete the module were sent to adults aged 50-74 years who were overdue for colorectal cancer screening and to women aged 40-49 years and men aged 55-69 who had not undergone a recent mammogram or prostate-specific antigen test, respectively., Results: The module was started by 2,355 patients and completed by 903 patients. Most respondents (76.8%) knew they were eligible for screening. Preferred next steps were talking to the clinician (76.6%), reading/research (28.6%), and consulting trusted friends/family (16.4%). Priority topics included how much screening improves life expectancy, comparative test performance, and the prevalence/health risks of the cancer. Leading fears were getting cancer/delayed detection (79.2%), abnormal results (40.5%), and testing complications (39.1%), the last referring to false test results, medical complications, or unnecessary treatments. Men eligible for prostate-specific antigen screening were more likely than women eligible for mammography to express concerns about testing complications and to prioritize weighing pros and cons over gut feelings (p<0.05)., Conclusions: Although this sample was predisposed to screening, most patients wanted help in finalizing their decision. Many wanted to weigh the pros and cons and expressed fears of potential harms from screening. Understanding how patients approach decisions may help design more effective engagement strategies., (Copyright © 2017 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

A metric was developed to identify hospital proportion of carbapenem consumption (PoCC) among antipseudomonal antibiotics. The PoCC varied significantly among academic medical centers by Census Bureau geographic division after adjusting for patient mix. This metric may be useful in identifying disproportionate carbapenem use and potential carbapenem overuse. Infect Control Hosp Epidemiol 2018;39:229-232.

Introduction: This study examines how improving curricular content and technical interface issues could make maintenance of certification activities more meaningful to American Board of Family Medicine diplomates completing Maintenance of Certification for Family Physicians (MC-FP) Program self-assessment modules (SAMs)., Methods: We used a sequential exploratory design to analyze quantitative and qualitative data from 320,500 surveys of family physicians who completed a SAM between January 2004 and April 2013. This included numeric rating scales and free text comments. Basic statistical rankings, template-based automated coding, and emergent coding were used to analyze SAM experience and identify thematic content., Results: Across SAMs, numeric ratings were universally high and positive free text comments outnumbered negative comments two to one. When comparing feedback on the knowledge assessment and clinical simulation (CS) activities, SAMs were rated less favorably when the frequency of ideas identified by participants as most prevalent in one activity mismatched those identified as most prevalent in the companion activity. Participants were also critical of navigation issues, technical issues, and a lack of realness in the CS activity., Discussion: Whether analyzed through quantitative data, qualitative data, or mixed methods, a large majority of participants rated their experience with SAMs highly. When individual SAMs were rated poorly, it seemed to be due to discordance in ideas emphasized between the knowledge assessment and CS components, or an opinion regarding the SAM topic that existed independent of the SAM process.

Purpose: Technology could transform routine decision making by anticipating patients' information needs, assessing where patients are with decisions and preferences, personalizing educational experiences, facilitating patient-clinician information exchange, and supporting follow-up. This study evaluated whether patients and clinicians will use such a decision module and its impact on care, using 3 cancer screening decisions as test cases., Methods: Twelve practices with 55,453 patients using a patient portal participated in this prospective observational cohort study. Participation was open to patients who might face a cancer screening decision: women aged 40 to 49 who had not had a mammogram in 2 years, men aged 55 to 69 who had not had a prostate-specific antigen test in 2 years, and adults aged 50 to 74 overdue for colorectal cancer screening. Data sources included module responses, electronic health record data, and a postencounter survey., Results: In 1 year, one-fifth of the portal users (11,458 patients) faced a potential cancer screening decision. Among these patients, 20.6% started and 7.9% completed the decision module. Fully 47.2% of module completers shared responses with their clinician. After their next office visit, 57.8% of those surveyed thought their clinician had seen their responses, and many reported the module made their appointment more productive (40.7%), helped engage them in the decision (47.7%), broadened their knowledge (48.1%), and improved communication (37.5%)., Conclusions: Many patients face decisions that can be anticipated and proactively facilitated through technology. Although use of technology has the potential to make visits more efficient and effective, cultural, workflow, and technical changes are needed before it could be widely disseminated., (© 2017 Annals of Family Medicine, Inc.)

Purpose: The US Food and Drug Administration issued a boxed warning on all products containing a long-acting β-agonist (LABA) in March 2006, after the findings from a trial suggested an increased risk for death in patients treated with salmeterol monotherapy. Almost nothing is known about the impact of this warning on LABA prescribing patterns or on clinicians' approaches to asthma maintenance therapy., Methods: A cohort of asthmatic adults on LABA therapy was retrospectively identified from a Baltimore-area Medicaid data warehouse. Pharmacy claims were used for determining the utilization rates of all asthma maintenance medications. Rates from the 6-month period before the warning (September 1, 2005, to February 28, 2006) were compared with rates from a similar 6-month period 1 year afterward (September 1, 2006, to February 28, 2007). The demographic characteristics of patients who continued LABA use were compared with those of discontinuers. In LABA discontinuers, utilization of alternative maintenance drugs was assessed., Findings: In this cohort of 455 asthmatic patients, LABAs were prescribed only in combination with inhaled corticosteroids. Following the warning, 53% of patients discontinued LABA use, and the mean number of LABA prescription fills per patient decreased from 2.6 to 1.8 (P < 0.0001). Concurrently, the use of inhaled corticosteroids increased from 0.3 to 0.8 fills per patient (P < 0.0001). LABA continuers were younger (P = 0.0005), more likely to be black (P = 0.0079), and more consistent with LABA fills prewarning (P < 0.0001). Of the 243 LABA discontinuers, 155 were placed on no alternative maintenance therapy., Implications: The management of asthma changed significantly after the LABA warning. The use of LABAs combined with inhaled corticosteroids plummeted, while the use of inhaled corticosteroid monotherapy increased. More than half of patients who discontinued LABAs were not placed on alternative maintenance therapy., (Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.)

Previous research has shown that childhood body size is associated with blood pressure in adulthood, and that early and rapid growth rates are correlated with adverse cardiovascular outcomes. Our objectives are to estimate associations between childhood body size growth parameters and adult blood pressure, and to examine the effect of early attainment of critical growth milestones on adult blood pressure, relative to normal or late attainment. Lifetime height and body mass index (BMI) measurements in childhood, and systolic blood pressure (SBP) and diastolic blood pressure (DBP) measurements in adulthood are taken from participants in the Fels Longitudinal Study. Childhood growth curves are estimated separately for stature and BMI using the Preece-Baines and third-degree polynomial models, respectively. Associations between the resulting parameter estimates and adult blood pressure are then examined using linear mixed models. Our findings show that the ages of achievement of the stature-based growth onset and peak velocity, as well as the age of achievement of the BMI-based adiposity rebound, are negatively associated with adult blood pressure, implying that early height or BMI growth can lead to increased blood pressure in adulthood. There were subtle differences in these relationships based on age and gender, and also between SBP and DBP. These results expand on the existing literature, showing that not only childhood body size, but also the timing of childhood growth can have a deleterious effect on adult cardiovascular health.

We compare posterior and predictive estimators and probabilities in response-adaptive randomization designs for two- and three-group clinical trials with binary outcomes. Adaptation based upon posterior estimates are discussed, as are two predictive probability algorithms: one using the traditional definition, the other using a skeptical distribution. Optimal and natural lead-in designs are covered. Simulation studies show: efficacy comparisons lead to more adaptation than center comparisons, though at some power loss; skeptically predictive efficacy comparisons and natural lead-in approaches lead to less adaptation but offer reduced allocation variability. Though nuanced, these results help clarify the power-adaptation trade-off in adaptive randomization.

Background: Electronic surveys are convenient, cost effective, and increasingly popular tools for collecting information. While the online platform allows researchers to recruit and enroll more participants, there is an increased risk of participant dropout in Web-based research. Often, these dropout trends are simply reported, adjusted for, or ignored altogether., Objective: To propose a conceptual framework that analyzes respondent attrition and demonstrates the utility of these methods with existing survey data., Methods: First, we suggest visualization of attrition trends using bar charts and survival curves. Next, we propose a generalized linear mixed model (GLMM) to detect or confirm significant attrition points. Finally, we suggest applications of existing statistical methods to investigate the effect of internal survey characteristics and patient characteristics on dropout. In order to apply this framework, we conducted a case study; a seventeen-item Informed Decision-Making (IDM) module addressing how and why patients make decisions about cancer screening., Results: Using the framework, we were able to find significant attrition points at Questions 4, 6, 7, and 9, and were also able to identify participant responses and characteristics associated with dropout at these points and overall., Conclusions: When these methods were applied to survey data, significant attrition trends were revealed, both visually and empirically, that can inspire researchers to investigate the factors associated with survey dropout, address whether survey completion is associated with health outcomes, and compare attrition patterns between groups. The framework can be used to extract information beyond simple responses, can be useful during survey development, and can help determine the external validity of survey results., Competing Interests: Conflicts of Interest: None declared., (©Camille J Hochheimer, Roy T Sabo, Alex H Krist, Teresa Day, John Cyrus, Steven H Woolf. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 22.11.2016.)

Patient-centered health risk assessments (HRAs) that screen for unhealthy behaviors, prioritize concerns, and provide feedback may improve counseling, goal setting, and health. To evaluate the effectiveness of routinely administering a patient-centered HRA, My Own Health Report, for diet, exercise, smoking, alcohol, drug use, stress, depression, anxiety, and sleep, 18 primary care practices were randomized to ask patients to complete My Own Health Report (MOHR) before an office visit (intervention) or continue usual care (control). Intervention practice patients were more likely than control practice patients to be asked about each of eight risks (range of differences 5.3-15.8 %, p < 0.001), set goals for six risks (range of differences 3.8-16.6 %, p < 0.01), and improve five risks (range of differences 5.4-13.6 %, p < 0.01). Compared to controls, intervention patients felt clinicians cared more for them and showed more interest in their concerns. Patient-centered health risk assessments improve screening and goal setting.Trial RegistrationClinicaltrials.gov identifier: NCT01825746.

Purpose: To determine if there is a difference in toxicity and effectiveness between obese and non-obese patients who receive high-dose cyclophosphamide (Cy) prior to allogeneic hematopoietic stem cell transplant (allo-HCT)., Methods: Patients were included in this study if they were at least 18 years of age and received high-dose Cy in combination with total body irradiation (CyTBI) or busulfan (BuCy) prior to allo-HCT between 1 January 2008 and 29 February 2012. The primary endpoint was the difference in overall toxicity between obese and non-obese patients. Secondary objectives examined differences in effectiveness between groups assessed by relapse at day +100, relapse at 1 year, death at 1 year, chimerisms at days +30, +60, and +90, and incidence of acute graft versus host disease (aGVHD)., Results: Sixty-one patients met the inclusion criteria, 28 obese and 33 non-obese. Overall toxicity was greater in obese patients compared to non-obese patients (82% vs. 52%, OR 4.3 [95% CI 1.3-14.1]; p = 0.01), which was driven by a greater incidence of renal dysfunction (79% vs. 48%, OR 3.9 [95% CI 1.3-12.1]; p = 0.02). There were no differences in rates of grade 3 or 4 toxicity, hepatic dysfunction, or any measure of effectiveness between groups., Conclusion: Obese patients receiving high-dose Cy and allo-HCT are at increased risk for toxicity, although there appears to be no difference in the rate of relapse or survival between obese and non-obese patients., (© The Author(s) 2014.)

Objective: Previous studies have shown associations between body mass index and cardiac structure in both childhood and adulthood. Using Fels Longitudinal Study measurements, we investigate the relationships between a curtailed juvenile state and both adult cardiac structure and function., Methods: A linear mixed-effect repeated measure analysis of variance model is used to test if there is a relationship between juvenile state and each echocardiographic measurement., Results: The curtailed juvenile state is significantly associated with adult left ventricular mass index for both males and females. It is also significantly associated with the interventricular septal wall thickness index and relative wall thickness index for females. In both cases, early juvenile states led to more abnormal structural estimates in adulthood than did late juvenile states. Among cardiac function measurements such as left ventricular ejection fraction and left ventricular shortening fraction, left ventricular ejection fraction is significantly associated with the juvenile state for females., Conclusion: The curtailed juvenile state at the childhood may have a long-term adverse effect on adult cardiac structure and function abnormalities., Competing Interests: Author Disclosure Statement No competing financial interests exist.

Background: The study aims to compare how work-to-rest ratio (W:R) influences insulin sensitivity (S i ) and inflammatory responses following one session of sprint interval training (SIT)., Methods: Thirteen men and two women completed a cross-over comparison of two SIT interventions-Tabata (TAB), 10 × 20-s sprints/10-s rest, and Wingate (WIN), 5 × 30-s sprints with 270-s rest. IL-6, IL-10, and TNF-α were assessed at baseline, immediately following, and 1 h after SIT, as well as prior to the 24-h post-exercise oral glucose tolerance tests (OGTTs)., Results: Participants were 23.8 (±3.5) years old and 180.0 (±10.2) cm tall, weighed 78.5 (13.0) kg, and had 16.9 (±6.5) % body fat, with a mean VO 2Peak of 42.0 (±7.9) ml kg -1  min -1 . There were no differences in total work (kJ) between TAB (64.7 ± 12.0) and WIN (68.0 ± 15.0). Mean (±95 % CI) S i 24 h changed -2.8 (-5.1, -0.5) from baseline after TAB and -3.9 (-6.9, -0.9) after WIN. Cytokines were measured in pg ml -1 and expressed as mean change (±95 % CI). IL-6 increased significantly immediately following SIT for TAB 0.70 (0.23, 1.17), and WIN 1.11 (0.60, 1.62), and remained elevated 1 h post SIT for TAB 1.10 (0.37, 1.83), and WIN 0.95 (0.26, 1.65). IL-10 showed a significant positive change immediately following exercise for TAB 1.53 (0.77, 2.29) and WIN 1.59 (0.58, 2.59). TNF-α also increased immediately both TAB 3.26 (1.57, 4.96) and WIN 3.05 (0.56, 5.54) and was directly proportional to IL-10 ( r  = 0.64, p  < 0.0001)., Conclusions: W:R did not alter either the inflammatory or metabolic response following SIT nor does SIT improve 24-h S i , despite increased levels of IL-10.

Systems that evolve over time and follow mathematical laws as they evolve are called dynamical systems. Lymphocyte recovery and clinical outcomes in 41 allograft recipients conditioned using antithymocyte globulin (ATG) and 4.5-Gy total body irradiation were studied to determine if immune reconstitution could be described as a dynamical system. Survival, relapse, and graft-versus-host disease (GVHD) were not significantly different in 2 cohorts of patients receiving different doses of ATG. However, donor-derived CD3(+) cell reconstitution was superior in the lower ATG dose cohort, and there were fewer instances of donor lymphocyte infusion (DLI). Lymphoid recovery was plotted in each individual over time and demonstrated 1 of 3 sigmoid growth patterns: Pattern A (n = 15) had rapid growth with high lymphocyte counts, pattern B (n = 14) had slower growth with intermediate recovery, and pattern C (n = 10) had poor lymphocyte reconstitution. There was a significant association between lymphocyte recovery patterns and both the rate of change of donor-derived CD3(+) at day 30 after stem cell transplantation (SCT) and clinical outcomes. GVHD was observed more frequently with pattern A, relapse and DLI more so with pattern C, with a consequent survival advantage in patients with patterns A and B. We conclude that evaluating immune reconstitution after SCT as a dynamical system may differentiate patients at risk of adverse outcomes and allow early intervention to modulate that risk., (Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Diabetes is predicted to increase in incidence by 42% from 1995 to 2025. Although most adults with diabetes seek care from primary care practices, adherence to treatment guidelines in these settings is not optimal. Many practices lack the infrastructure to monitor patient adherence to recommended treatment and are slow to implement changes critical for effective management of patients with chronic conditions. Supporting Practices to Adopt Registry-Based Care (SPARC) will evaluate effectiveness and sustainability of a low-cost intervention designed to support work process change in primary care practices and enhance focus on population-based care through implementation of a diabetes registry., Methods: SPARC is a two-armed randomized controlled trial (RCT) of 30 primary care practices in the Virginia Ambulatory Care Outcomes Research Network (ACORN). Participating practices (including control groups) will be introduced to population health concepts and tools for work process redesign and registry adoption at a meeting of practice-level implementation champions. Practices randomized to the intervention will be assigned study peer mentors, receive a list of specific milestones, and have access to a physician informaticist. Peer mentors are clinicians who successfully implemented registries in their practices and will help champions in the intervention practices throughout the implementation process. During the first year, peer mentors will contact intervention practices monthly and visit them quarterly. Control group practices will not receive support or guidance for registry implementation. We will use a mixed-methods explanatory sequential design to guide collection of medical record, participant observation, and semistructured interview data in control and intervention practices at baseline, 12 months, and 24 months. We will use grounded theory and a template-guided approach using the Consolidated Framework for Implementation Research to analyze qualitative data on contextual factors related to registry adoption. We will assess intervention effectiveness by comparing changes in patient-level hemoglobin A1c scores from baseline to year 1 between intervention and control practices., Discussion: Findings will enhance our understanding of how to leverage existing practice resources to improve diabetes care in primary care practices by implementing and using a registry. SPARC has the potential to validate the effectiveness of low-cost implementation strategies that target practice change in primary care., Trial Registration: NCT02318108.

Background and Objectives: Medical student faculty advisors are charged with providing students the best possible information and advice regarding residency selection and how to increase their likelihood of matching into the program of their choice. Given the lack of clear and consistent processes for ranking residency applicants, medical student advisors will benefit from better insight into the perspectives of family medicine residency (FMR) faculty., Methods: This study was designed to increase understanding of the perceptions of FMR faculty in evaluating and ranking medical student applicants. We surveyed all FMR programs in the United States and Puerto Rico. Program directors, or their designees, were asked to provide basic program characteristics and then to either agree or disagree with various advising statements medical school faculty might say to students applying to FMR programs., Results: Of the 24 items in the survey, consensus among programs was reached for only seven., Conclusions: These results, especially given the current climate of an increasing number of applicants for a nearly stable number of residency training slots, clearly support the need for enhanced communication and collaboration between family medicine student advisors and residency educators.

Background: Evidence-based preventive services for early detection of cancer and other health conditions offer profound health benefits, yet Americans receive only half of indicated services. Policy initiatives promote the adoption of information technologies to engage patients in care. We developed a theory-driven interactive preventive health record (IPHR) to engage patients in health promotion. The model defines five levels of functionality: (1) collecting patient information, (2) integrating with electronic health records (EHRs), (3) translating information into lay language, (4) providing individualized, guideline-based clinical recommendations, and (5) facilitating patient action. It is hypothesized that personal health records (PHRs) with these higher levels of functionality will inform and activate patients in ways that simpler PHRs cannot. However, realizing this vision requires both technological advances and effective implementation based upon clinician and practice engagement., Methods/design: We are starting a two-phase, mixed-method trial to evaluate whether the IPHR is scalable across a large number of practices and how its uptake differs for minority and disadvantaged patients. In phase 1, 40 practices from three practice-based research networks will be randomized to add IPHR functionality to their PHR versus continue to use their existing PHR. Throughout the study, we will engage intervention practices to locally tailor IPHR content and learn how to integrate new functions into their practice workflow. In phase 2, the IPHR to all nonintervention practices to observe whether the IPHR can be implemented more broadly (Scalability). Phase 1 will feature an implementation assessment in intervention practices, based on the RE-AIM model, to measure Reach (creation of IPHR accounts by patients), Adoption (practice decision to use the IPHR), Implementation (consistency, fidelity, barriers, and facilitators of use), and Maintenance (sustained use). The incremental effect of the IPHR on receipt of cancer screening tests and shared decision-making compared to traditional PHRs will assess Effectiveness. In phase 2, we will assess similar outcomes as phase 1 except for effectiveness., Discussion: This study will yield information about the effectiveness of new health information technologies designed to actively engage patients in their care as well as information about how to effectively implement and disseminate PHRs by engaging clinicians., Trial Registration: ClinicalTrials.gov: NCT02138448.

Outcomes in stem cell transplantation (SCT) are modeled using probability theory. However, the clinical course following SCT appears to demonstrate many characteristics of dynamical systems, especially when outcomes are considered in the context of immune reconstitution. Dynamical systems tend to evolve over time according to mathematically determined rules. Characteristically, the future states of the system are predicated on the states preceding them, and there is sensitivity to initial conditions. In SCT, the interaction between donor T cells and the recipient may be considered as such a system in which, graft source, conditioning, and early immunosuppression profoundly influence immune reconstitution over time. This eventually determines clinical outcomes, either the emergence of tolerance or the development of graft versus host disease. In this paper, parallels between SCT and dynamical systems are explored and a conceptual framework for developing mathematical models to understand disparate transplant outcomes is proposed.

Purpose: Guidelines recommend screening patients for unhealthy behaviors and mental health concerns. Health risk assessments can systematically identify patient needs and trigger care. This study seeks to evaluate whether primary care practices can routinely implement such assessments into routine care., Methods: As part of a cluster-randomized pragmatic trial, 9 diverse primary care practices implemented My Own Health Report (MOHR)-an electronic or paper-based health behavior and mental health assessment and feedback system paired with counseling and goal setting. We observed how practices integrated MOHR into their workflows, what additional practice staff time it required, and what percentage of patients completed a MOHR assessment (Reach)., Results: Most practices approached (60%) agreed to adopt MOHR. How they implemented MOHR depended on practice resources, informatics capacity, and patient characteristics. Three practices mailed patients invitations to complete MOHR on the Web, 1 called patients and completed MOHR over the telephone, 1 had patients complete MOHR on paper in the office, and 4 had staff help patients complete MOHR on the Web in the office. Overall, 3,591 patients were approached and 1,782 completed MOHR (Reach = 49.6%). Reach varied by implementation strategy with higher reach when MOHR was completed by staff than by patients (71.2% vs 30.2%, P <.001). No practices were able to sustain the complete MOHR assessment without adaptations after study completion. Fielding MOHR increased staff and clinician time an average of 28 minutes per visit., Conclusions: Primary care practices can implement health behavior and mental health assessments, but counseling patients effectively requires effort. Practices will need more support to implement and sustain assessments., (© 2014 Annals of Family Medicine, Inc.)

Purpose: To describe the frequency and patient-reported readiness to change, desire to discuss, and perceived importance of 13 health risk factors in a diverse range of primary care practices., Methods: Patients (n = 1,707) in 9 primary care practices in the My Own Health Report (MOHR) trial reported general, behavioral, and psychosocial risk factors (body mass index [BMI], health status, diet, physical activity, sleep, drug use, stress, anxiety or worry, and depression). We classified responses as "at risk" or "healthy" for each factor, and patients indicated their readiness to change and/or desire to discuss identified risk factors with providers. Patients also selected 1 of the factors they were ready to change as most important. We then calculated frequencies within and across these factors and examined variation by patient characteristics and across practices., Results: On average, patients had 5.8 (SD = 2.12; range, 0-13) unhealthy behaviors and mental health risk factors. About 55% of patients had more than 6 risk factors. On average, patients wanted to change 1.2 and discuss 0.7 risks. The most common risks were inadequate fruit/vegetable consumption (84.5%) and overweight/obesity (79.6%). Patients were most ready to change BMI (33.3%) and depression (30.7%), and most wanted to discuss depression (41.9%) and anxiety or worry (35.2%). Overall, patients rated health status as most important., Conclusions: Implementing routine comprehensive health risk assessments in primary care will likely identify a high number of behavioral and psychosocial health risks. By soliciting patient priorities, providers and patients can better manage counseling and behavior change., (© 2014 Annals of Family Medicine, Inc.)

Objectives: To determine whether childhood body size, composition and blood pressure are associated with adult cardiac structure by estimating childhood "age of divergence.", Methods: 385 female and 312 male participants in the Fels Longitudinal Study had echocardiographic measurements of left ventricular mass, relative wall thickness, and interventricular septal thickness. Also available were anthropometric measurements of body mass index, waist circumference, percentage body fat, fat free mass, total body fat, and systolic and diastolic blood pressures, taken in both childhood and adulthood. The age of divergence is estimated as the lowest age at which childhood measurements are significantly different between patients with low and high measurements of adult cardiac structure., Results: Childhood body mass index is significantly associated with adult left ventricular mass (indexed by height) in men and women (ages of divergence: 7.5 years and 11.5 years, respectively), and with adult interventricular septal thickness in boys (age of divergence: 9 years). Childhood waist circumference indexed by height is associated with left ventricular mass (indexed by height) in boys (age of divergence: 8 years). Cardiac structure was in general not associated with childhood body composition and blood pressure., Conclusions: Though results are affected by adult body size, composition and blood pressure, some aspects of adult cardiac structure may have their genesis in childhood body size.

Purpose: Health care leaders encourage clinicians to offer portals that enable patients to access personal health records, but implementation has been a challenge. Although large integrated health systems have promoted use through costly advertising campaigns, other implementation methods are needed for small to medium-sized practices where most patients receive their care., Methods: We conducted a mixed methods assessment of a proactive implementation strategy for a patient portal (an interactive preventive health record [IPHR]) offered by 8 primary care practices. The practices implemented a series of learning collaboratives with practice champions and redesigned workflow to integrate portal use into care. Practice implementation strategies, portal use, and factors influencing use were assessed prospectively., Results: A proactive and customized implementation strategy designed by practices resulted in 25.6% of patients using the IPHR, with the rate increasing 1.0% per month over 31 months. Fully 23.5% of IPHR users signed up within 1 day of their office visit. Older patients and patients with comorbidities were more likely to use the IPHR, but blacks and Hispanics were less likely. Older age diminished as a factor after adjusting for comorbidities. Implementation by practice varied considerably (from 22.1% to 27.9%, P <.001) based on clinician characteristics and workflow innovations adopted by practices to enhance uptake., Conclusions: By directly engaging patients to use a portal and supporting practices to integrate use into care, primary care practices can match or potentially surpass the usage rates achieved by large health systems., (© 2014 Annals of Family Medicine, Inc.)

A method of outcome-adaptive allocation is presented using Bayes methods, where a natural lead-in is incorporated through the use of informative yet skeptical prior distributions for each treatment group. These prior distributions are modeled on unobserved data in such a way that their influence on the allocation scheme decreases as the trial progresses. Simulation studies show this method to behave comparably to the Bayesian adaptive allocation method described by Thall and Wathen (2007), who incorporate a natural lead-in through sample-size-based exponents.

Background: There is a pressing need for greater attention to patient-centered health behavior and psychosocial issues in primary care, and for practical tools, study designs and results of clinical and policy relevance. Our goal is to design a scientifically rigorous and valid pragmatic trial to test whether primary care practices can systematically implement the collection of patient-reported information and provide patients needed advice, goal setting, and counseling in response., Methods: This manuscript reports on the iterative design of the My Own Health Report (MOHR) study, a cluster randomized delayed intervention trial. Nine pairs of diverse primary care practices will be randomized to early or delayed intervention four months later. The intervention consists of fielding the MOHR assessment--addresses 10 domains of health behaviors and psychosocial issues--and subsequent provision of needed counseling and support for patients presenting for wellness or chronic care. As a pragmatic participatory trial, stakeholder groups including practice partners and patients have been engaged throughout the study design to account for local resources and characteristics. Participatory tasks include identifying MOHR assessment content, refining the study design, providing input on outcomes measures, and designing the implementation workflow. Study outcomes include the intervention reach (percent of patients offered and completing the MOHR assessment), effectiveness (patients reporting being asked about topics, setting change goals, and receiving assistance in early versus delayed intervention practices), contextual factors influencing outcomes, and intervention costs., Discussion: The MOHR study shows how a participatory design can be used to promote the consistent collection and use of patient-reported health behavior and psychosocial assessments in a broad range of primary care settings. While pragmatic in nature, the study design will allow valid comparisons to answer the posed research question, and findings will be broadly generalizable to a range of primary care settings. Per the pragmatic explanatory continuum indicator summary (PRECIS) framework, the study design is substantially more pragmatic than other published trials. The methods and findings should be of interest to researchers, practitioners, and policy makers attempting to make healthcare more patient-centered and relevant., Trial Registration: Clinicaltrials.gov: NCT01825746.

Increases in vector-host contact rates can enhance arbovirus transmission intensity. We investigated weekly fluctuations in contact rates between mosquitoes and nesting birds using the recently described Nest Mosquito Trap (NMT). The number of mosquitoes per nestling increased from < 1 mosquito per trap night to 36.2 in the final 2 wk of the nesting season. Our evidence suggests the coincidence of the end of the avian nesting season and increasing mosquito abundances may have caused a "host funnel," concentrating host-seeking mosquitoes to the few remaining nestlings. The relative abundance of mosquitoes collected by the NMT suggests that significantly more Aedes albopictus (Skuse) and Culex pipiens (L.) /restuans (Theobald) sought nesting bird bloodmeals than were predicted by their relative abundances in CO2-baited Centers for Disease Control and Prevention light and gravid traps. Culex salinarius (Coquillett) and Culex erraticus Dyar and Knab were collected in NMTs in proportion to their relative abundances in the generic traps. Temporal host funnels and nesting bird host specificity may enhance arbovirus amplification and explain observed West Nile virus and St. Louis encephalitis virus amplification periods.

Rabbit anti-thymocyte globulin (ATG) is used as prophylaxis against GVHD following allogeneic hematopoietic cell transplantation (HCT). At our institution, ATG is exclusively used in the conditioning of matched unrelated donor (URD) transplant recipients. A total of 50 URD HCT recipients who received ATG (ATG group) were retrospectively compared with 48 matched related donor (MRD) HCT recipients who did not receive ATG (no ATG group). There were no significant differences between the groups in rates of day 100 mortality, acute GVHD or relapse. Chronic GVHD incidence was significantly lower in the ATG group (P = 0.007). At a median follow-up of 36 months in the entire cohort, 50% patients are alive in the ATG group and 63% of the patients are alive in the no ATG group (P = 0.13). We conclude that the administration of ATG to patients undergoing URD HCT preserves the anti-leukemia benefit of the transplant, while reducing the risk of developing GVHD, resulting in OS rates that are comparable to MRD HCT recipients.

Patients with multiple myeloma (MM) undergoing high dose therapy and autologous stem cell transplantation (SCT) remain at risk for disease progression. Induction of the expression of highly immunogenic cancer testis antigens (CTA) in malignant plasma cells in MM patients may trigger a protective immune response following SCT. We initiated a phase II clinical trial of the DNA hypomethylating agent, azacitidine (Aza) administered sequentially with lenalidomide (Rev) in patients with MM. Three cycles of Aza and Rev were administered and autologous lymphocytes were collected following the 2nd and 3rd cycles of Aza-Rev and cryopreserved. Subsequent stem cell mobilization was followed by high-dose melphalan and SCT. Autologous lymphocyte infusion (ALI) was performed in the second month following transplantation. Fourteen patients have completed the investigational therapy; autologous lymphocytes were collected from all of the patients. Thirteen patients have successfully completed SCT and 11 have undergone ALI. Six patients tested have demonstrated CTA up-regulation in either unfractionated bone marrow (n = 4) or CD138+ cells (n = 2). CTA (CTAG1B)-specific T cell response has been observed in all three patients tested and persists following SCT. Epigenetic induction of an adaptive immune response to cancer testis antigens is safe and feasible in MM patients undergoing SCT., (© 2012 Blackwell Publishing Ltd.)

Background: Evidence shows that some causes of the metabolic syndrome (MS) begin in childhood, which could indicate a familial association, through either genetic inheritance or cohabitation., Objective: This study examined associations between parents and adult offspring diagnoses of the MS and its risk factors., Design: Measurements were obtained from adult participants and their adult offspring enrolled in the Fels Longitudinal Study, with simultaneous waist circumference, systolic blood pressure (SBP), diastolic blood pressure (DBP), triglycerides, HDL, and glucose observations used for diagnosis. On the basis of repeated measurements (in some cases), adult participants were classified as having the MS at least once or as never having the MS. Chi-square tests, ORs, and mixed-effects models were used to study familial associations., Results: Maternal (OR: 2.5; 95% CI: 1.1, 5.5) and paternal (OR: 4.1; 95% CI: 1.4, 12.1) MS classifications were significantly associated with MS classification in sons. MS classification in mothers and daughters (OR: 2.7; 95% CI: 0.9, 8.7; P = 0.08) was similar to that in sons but was not significant, whereas fathers and daughters were not associated (OR: 1.1; 95% CI: 0.4, 3.5). Maternal MS diagnoses were significantly and positively associated with triglycerides in male offspring and were significantly associated with SBP, DBP, and triglycerides in females. Paternal diagnoses were significantly associated only with DBP and HDL in male offspring., Conclusions: Parental MS diagnosis is significantly associated with MS diagnosis in adult male offspring, and adverse levels of certain risk factors are associated between offspring and parents, although these associations vary across risk factors and child sex.

Previous studies estimated critical periods of childhood BMI growth and linked these events to adult adiposity and cardiovascular health. We expand upon both results to link childhood BMI growth patterns with adult blood pressure (BP). Data from male and female participants in the Fels Longitudinal Study (FLS) were used to estimate childhood BMI growth curves, from which we isolate ages of childhood BMI divergence based upon adult BMI and BP measurements. Repeated measure analysis of variances models were used to estimate BMI growth curves from age 2 to age 17.5 based on both adult BMI (< 25 kg/m(2) or ≥ 25 kg/m(2)) and adult BP (< 120 mm Hg or ≥ 120 mm Hg for systolic BP (SBP); < 80 mm Hg or ≥ 80 mm Hg for diastolic BP (DBP)). Participants with lower body weight throughout childhood had lower SBP and DBP in early adulthood. Any relationships between childhood adiposity and adult body weight and BP disappeared by age 60. These results were independent of adult BMI and were observed in both men and women. Increased adult BP has its genesis in part from increased childhood BMI.

Objectives: While researchers are increasingly recognizing the importance of adjusting waist circumference (WC) for height, no standard has yet been established. In this study we contrast three standard methods for indexing WC by height (using height, root-height and height-squared) via comparisons with age-specific optimal indices., Study Design and Setting: Measurements from 722 male and 746 female Caucasian participants in the Fels Longitudinal Study were used. The three standard waist-circumference indices (as well as an optimal index) were determined for ages 2 through 18, and for every decade thereafter to 70 years of age. Pearson correlations were used to assess the suitability of all indices., Results: The three standard indices remain correlated with the original WC measures, though each was associated with height at some ages. Waist-to-height ratio is suitable for some childhood ages (boys: 5 - 9, 13 - 16; girls: 4 - 7, 9, 11 - 14) but not for adult ages; Root-height works well mostly for older teenage children and adults but not in early childhood and adolescence; Height-squared is nowhere suitable. In both men and women, the optimal indexing factor ranged between root-height and height-squared in childhood, and is close to root-height in adulthood., Conclusions: No one index is most suitable, as WC indexed by root-height is suitable for use with measurements from teenage children and adults, while waist-to-height ratio is generally suitable for use in children. WC indexed by height-squared is nowhere suitable.

Background: In patients with hematologic malignancies who receive stem-cell transplantation, donors' T cells can recognize minor histocompatibility antigens on recipient cells and generate an objective response against the tumor. However, a major side effect of such therapy is graft-versus-host disease (GVHD). The purpose of this study was to characterize distinct T-cell clones that were frequently and exclusively involved in GVHD or graft-versus-tumor (GVT) effects., Methods: We hypothesized that distinct GVHD-associated T-cell clones can be identified during the disease progression. To test this, we conducted comparative analysis of T-cell receptor (TCR) Vβs in donor-recipient pairs of patients with GVHD versus those with GVHD-free and relapse-free survival using quantitative reverse-transcriptase polymerase chain reaction and spectratyping analyses., Results: We identified three sets of T-cell clones that were either frequently involved in GVHD (TCR Vβ4, 11, and 23) or GVT effect (TCR Vβ9, 16, and 20), or were increased at the time of GVHD and GVT effects in a patient-specific manner (TCR Vβ2, 3, 7, 12, 15, and 17). Spectratyping analysis showed restricted clonality of the identified TCR Vβs. Polymerase chain reaction analysis also confirmed the presence of GVHD-associated T-cell clones at the site of the disease., Conclusions: These data suggest that GVHD- and GVT-associated clones can be distinguished by molecular analysis of TCR Vβ to develop targeted therapy for GVHD.

Patients with hematologic malignancies were conditioned using a rabbit antithymocyte globulin-based reduced-intensity conditioning regimen for allogeneic stem cell transplantation. Donor-derived CD3(+) cell count (ddCD3), a product of CD3(+) cell chimerism and absolute CD3(+) cell count, when <110/μL at 8 weeks post-stem cell transplantation predicted a high risk of sustained mixed chimerism and relapse. Alternatively, patients with a higher ddCD3 developed graft-versus-host disease more frequently, and when partially chimeric, had higher rates of conversion to full donor chimerism after withdrawal of immunosuppression. Early data from our small cohort of patients indicate that ddCD3 at 8 weeks may be used to guide decisions regarding withdrawal of immunosuppression and administration of donor lymphocyte infusion in partially T cell-depleted reduced-intensity regimens., (Published by Elsevier Inc.)

Background: The usefulness of glucocorticoids after cardiac surgery with cardiopulmonary bypass has been a matter of debate for many years. Exposure to cardiopulmonary bypass evokes the systemic inflammatory response syndrome in patients undergoing cardiac surgery. Intravenous glucocorticoids have been used to reduce proinflammatory cytokine release, slow leukocyte migration, and decrease capillary leak associated with cardiopulmonary bypass., Objective: To assess the impact of early postoperative hydrocortisone administration on duration of vasoactive medication administration and the incidence of postoperative atrial fibrillation in cardiac surgical patients after cardiopulmonary bypass., Methods: A retrospective cohort study (between July 1, 2004, and June 30, 2008) was conducted at a large, university-affiliated, tertiary-care medical center. One-hundred forty-seven patients who underwent cardiac surgery with cardiopulmonary bypass, 72 of whom received at least 1 dose of hydrocortisone (treatment), and 75 similar patients who did not receive hydrocortisone (control), were randomly selected., Results: Cardiopulmonary bypass and aortic cross-clamp times were similar between treatment and control groups (128 vs 124 minutes, p = 0.56; 103 vs 98 minutes, p = 0.39). Patients who received hydrocortisone had a significantly shorter time to discontinuation of all vasoactive medications (79.6 vs 21.1 hours, p < 0.001), and less postoperative atrial fibrillation (OR 0.28, 95% CI 0.14 to 0.56, p < 0.001). Patients in the treatment group experienced significantly more hyperglycemia (89 vs 71%, p = 0.006); however, major and minor bleeding or infection rates did not differ significantly between groups., Conclusions: Patients treated with hydrocortisone after cardiac surgery with cardiopulmonary bypass experienced a significantly shorter time to discontinuation of all vasoactive medications and less postoperative atrial fibrillation than patients not treated with hydrocortisone. These benefits came at the expense of significantly more hyperglycemia., (© 2011 SAGE Publications.)

Objectives: Several studies have shown that causes of adult hypertension arise in childhood, and obesity may be a potential cause or at least a mitigating factor in this development. Body mass index is a well studied obesity metric, yet other potential adiposity measures such as percent body fat and waist circumference have been somewhat less considered. The purpose of this study is to determine associations between these alternative serial childhood adiposity measures and adulthood blood pressure., Methods: Measurements from participants in the Fels Longitudinal Study were used to summarize childhood adiposity, represented by childhood measurements of percent body fat and height-adjusted waist circumference. These subjects also provided systolic and diastolic blood pressure as adults. Childhood adiposity levels were categorized as high or low as compared to the respective upper quartile, and associations with adult blood pressure were measured using Poisson regression to estimate the number of expected occurrences of elevated adiposity during childhood. Adult lifestyle covariates and adiposity were accounted for using multiple linear regression., Results: Summary indices of the childhood adiposity measures were significantly associated with both adult blood pressure metrics in men and women, though some of these associations were altered or reduced in the presence of adult lifestyle characteristics and adult adiposity measures., Conclusions: Childhood measures of percent body fat and height-adjusted waist circumference have an effect on adult blood pressure, though the effect can be mitigated by adult lifestyles., (© 2010 Wiley-Liss, Inc.)

The analysis of repeated measure or clustered data is often complicated by the presence of correlation. Further complications arise for discrete responses, where the marginal probability-dependent Fréchet bounds impose feasibility limits on the correlation that are often more restrictive than the positive definite range. Some popular statistical methods, such as generalized estimating equations (GEE), ignore these bounds, and as such can generate erroneous estimates and lead to incorrect inferential results. In this paper, we discuss two alternative strategies: (i) using QIC to select a data-driven correlation value within the Fréchet bounds, and (ii) the use of likelihood-based latent variable modeling, such as multivariate probit, to get around the problem all together. We provide two examples of the repercussions of incorrectly using existing GEE software in the presence of correlated binary responses., (Copyright © 2010 John Wiley & Sons, Ltd.)

Unlabelled: Between January 2000 and May 2003, 50 consecutive Charcot diabetic salvage procedures were performed on 44 patients (average age 55.1 years). Twenty-four women (26 feet) and 20 men (24 feet) underwent a reconstructive limb salvage procedure for diabetic Charcot neuroarthropathy using a systematic surgical approach involving internal and external fixation. A retrospective analysis of patient satisfaction and clinical outcome was evaluated over a 2- to 5-year postoperative period; 75% of patients completed the SF-36 health survey and a patient satisfaction survey. A reliability analysis found the SF-36 survey to be an adequate health measurement tool in this Charcot neuroarthropathy cohort. Analysis of variance and categorical data analysis showed that the patients improved statistically significantly in response to surgical intervention; however, none of the demographic variables was statistically significantly associated with patient outcomes as measured by the SF-36 and the patient satisfaction survey., Level of Clinical Evidence: 2.