Roy T. Sabo

Designing a valid randomized pragmatic primary care implementation trial: The my own health report (MOHR) project

BackgroundThere 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.MethodsThis 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.DiscussionThe 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 registrationClinicaltrials.gov: NCT01825746

Engaging Primary Care Patients to Use a Patient-Centered Personal Health Record

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.

A retrospective analysis of 50 consecutive Charcot diabetic salvage reconstructions.

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.

Epigenetic induction of adaptive immune response in multiple myeloma: sequential azacitidine and lenalidomide generate cancer testis antigen‐specific cellular immunity

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.

Adoption, reach, implementation, and maintenance of a behavioral and mental health assessment in primary care.

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.

Serial Childhood BMI and Associations With Adult Hypertension and Obesity: The Fels Longitudinal Study

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/m2 or ≥ 25 kg/m2) 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.

Secular trends in body composition for children and young adults: the Fels Longitudinal Study.

To determine secular trends by birth decade in body mass index (BMI), waist circumference/height (W/Ht), percent body fat (PBF), and fat‐free mass adjusted for height squared (FFM/Ht2) in children and adolescents aged 8–18 years.

Frequency and Prioritization of Patient Health Risks from a Structured Health Risk Assessment

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.

Distinct oligoclonal T cells are associated with graft versus host disease after stem-cell transplantation.

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) V&bgr;s 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 V&bgr;4, 11, and 23) or GVT effect (TCR V&;9, 16, and 20), or were increased at the time of GVHD and GVT effects in a patient-specific manner (TCR V&bgr;2, 3, 7, 12, 15, and 17). Spectratyping analysis showed restricted clonality of the identified TCR V&bgr;s. 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 V&bgr; to develop targeted therapy for GVHD.

Favorable Outcomes in Patients with High Donor-Derived T Cell Count after In Vivo T Cell–Depleted Reduced-Intensity Allogeneic Stem Cell Transplantation

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.