Real-world cohort study of adult and pediatric patients treated for hereditary angioedema in the United States.

Background: There is limited real-world evidence on hereditary angioedema (HAE) patient characteristics and health-care resource utilization (HCRU); in addition, pediatric patients have been described in small cohorts. Objective: To describe patient characteristics, treatment patterns, and HCRU among adult and pediatric patients treated for HAE in a large U.S. cohort. Methods: This retrospective cohort study used an administrative claims data base (January 2006 to September 2015). Eligible patients with either ≥1 pharmacy claim for HAE-indicated therapies (C1 inhibitors, ecallantide, icatibant) or ≥2 medical claims with codes associated with HAE (per medical billing codes), and ≥1 claim for androgens, fresh frozen plasma, tranexamic acid, or ε-aminocaproic acid formed a "treated cohort." Three nonexclusive treated cohorts were assessed: overall, pediatric, and HCRU (≥2 years of continuous enrollment during 2010-2015). Results: Overall, 1429 patients received treatment (mean ± standard deviation [SD] age, 38.8 ±15.7 years; 62.4% female patients; mean ± SD Charlson Comorbidity Index of 1.4 ± 2.4). Common comorbidities were allergy or anaphylaxis (51.4%) and anxiety or depression (35.8%). Diagnoses indicative of HAE attacks included swelling and/or angioedema (78.5%), abdominal pain (55.6%), and asphyxiation (27.2%). Use of HAE-indicated medication rose between 2006 and 2015 to 81.8%, whereas androgen use declined (from 91.5% to 24.9%). Similar trends were observed in the pediatric treated cohort (n = 143). In the HCRU treated cohort (n = 538), HAE-related claims for emergency department and inpatient admissions were observed for 36.6% and 22.3% of patients, respectively. Conclusion: In a large U.S. cohort of adult and pediatric patients who received treatments indicated or used for HAE, common comorbidities and trends in resource use denoted the substantial burden of attacks, which reflected a continued need that recently approved long-term prophylactic treatments may help to address.

Informing real-world practice with real-world evidence: the value of PRECIS-2.

Real-world evidence is needed to inform real-world practice. Pragmatic controlled trials are intended to provide such evidence by assessing the effectiveness of medicines and other interventions in real-world settings, as opposed to explanatory trials that assess efficacy in highly controlled settings. Dal-Ré and colleagues (BMC Med 16:49, 2018) recently performed a literature review of studies published between 2014 and 2017 to assess the degree to which studies that self-identified as pragmatic were truly so. The authors found that over one-third of randomized controlled trials of drugs and biologics that were self-labeled as pragmatic used placebo controls (as opposed to usual care), tested medicines before licensing, or were conducted in a single site. Further, they proposed that, in order to improve the reliability of the 'pragmatic' label, investigators should assess their trials using the PRECIS-2 tool upon submission to funders, ethics boards, or journals. We appreciate the value of PRECIS-2 as an indicator to assess the pragmatic versus explanatory features in a trial, and we herein highlight the potential challenges and opportunities that may arise with its systematic and widespread use.

Facilitative Components of Collaborative Learning: A Review of Nine Health Research Networks.

OBJECTIVE: Collaborative research networks are increasingly used as an effective mechanism for accelerating knowledge transfer into policy and practice. This paper explored the characteristics and collaborative learning approaches of nine health research networks. DATA SOURCES/STUDY SETTING: Semi-structured interviews with representatives from eight diverse US health services research networks conducted between November 2012 and January 2013 and program evaluation data from a ninth. STUDY DESIGN: The qualitative analysis assessed each network's purpose, duration, funding sources, governance structure, methods used to foster collaboration, and barriers and facilitators to collaborative learning. DATA COLLECTION: The authors reviewed detailed notes from the interviews to distill salient themes. PRINCIPAL FINDINGS: Face-to-face meetings, intentional facilitation and communication, shared vision, trust among members and willingness to work together were key facilitators of collaborative learning. Competing priorities for members, limited funding and lack of long-term support and geographic dispersion were the main barriers to coordination and collaboration across research network members. CONCLUSION: The findings illustrate the importance of collaborative learning in research networks and the challenges to evaluating the success of research network functionality. Conducting readiness assessments and developing process and outcome evaluation metrics will advance the design and show the impact of collaborative research networks.

Trials without tribulations: Minimizing the burden of pragmatic research on healthcare systems.

Pragmatic clinical trials are increasingly common because they have the potential to yield findings that are directly translatable to real-world healthcare settings. Pragmatic clinical trials need to integrate research into clinical workflow without placing an undue burden on the delivery system. This requires a research partnership between investigators and healthcare system representatives. This paper, organized as a series of case studies drawn from our experience in the NIH Health Care Systems Research Collaboratory, presents guidance from informational interviews of physician-scientists, health services researchers, and delivery system leaders who recently launched pragmatic clinical trials.

Promoting Patient and Family Partnerships in Ambulatory Care Improvement: A Narrative Review and Focus Group Findings.

INTRODUCTION: Ambulatory practices that actively partner with patients and families in quality improvement (QI) report benefits such as better patient/family interactions with physicians and staff, and patient empowerment. However, creating effective patient/family partnerships for ambulatory care improvement is not yet routine. The objective of this paper is to provide practices with concrete evidence about meaningfully involving patients and families in QI activities. METHODS: Review of literature published from 2000-2015 and a focus group conducted in 2014 with practice advisors. RESULTS: Thirty articles discussed 26 studies or examples of patient/family partnerships in ambulatory care QI. Patient and family partnership mechanisms included QI committees and advisory councils. Facilitators included process transparency, mechanisms for acting on patient/family input, and compensation. Challenges for practices included uncertainty about how best to involve patients and families in QI. Several studies found that patient/family partnership was a catalyst for improvement and reported that partnerships resulted in process improvements. Focus group results were concordant. CONCLUSION: This paper describes emergent mechanisms and processes that ambulatory care practices use to partner with patients and families in QI including outcomes, facilitators, and challenges. FUNDING: Gordon and Betty Moore Foundation.

Use of PRECIS ratings in the National Institutes of Health (NIH) Health Care Systems Research Collaboratory.

BACKGROUND: The National Institutes of Health (NIH) Health Care Systems Research Collaboratory (NIH Collaboratory) seeks to produce generalizable knowledge about the conduct of pragmatic research in health systems. This analysis applied the PRECIS-2 pragmatic trial criteria to five NIH Collaboratory pragmatic trials to better understand 1) the pragmatic aspects of the design and implementation of treatments delivered in real world settings and 2) the usability of the PRECIS-2 criteria for assessing pragmatic features across studies and across time. METHODS/DESIGN: Using the PRECIS-2 criteria, five pragmatic trials were each rated by eight raters. For each trial, we reviewed the original grant application and a required progress report written at the end of a 1-year planning period that included changes to the protocol or implementation approach. We calculated median scores and interrater reliability for each PRECIS domain and for the overall trial at both time points, as well as the differences in scores between the two time points. We also reviewed the rater comments associated with the scores. RESULTS: All five trials were rated to be more pragmatic than explanatory, with comments indicating that raters generally perceived them to closely mirror routine clinical care across multiple domains. The PRECIS-2 domains for which the trials were, on average, rated as most pragmatic on the 1 to 5 scale at the conclusion of the planning period included primary analysis (mean = 4.7 (range = 4.5 to 4.9)), recruitment (4.3 (3.6 to 4.8)), eligibility (4.1 (3.4 to 4.8)), setting (4.1 (4.0 to 4.4)), follow-up (4.1 (3.4 to 4.9)), and primary outcome (4.1 (3.5 to 4.9)). On average, the less pragmatic domains were organization (3.3 (2.6 to 4.4)), flexibility of intervention delivery (3.5 (2.1-4.5)), and flexibility of intervention adherence (3.8 (2.8-4.5)). Interrater agreement was modest but statistically significant for four trials (Gwet's AC1 statistic range 0.23 to 0.40) and the intraclass correlation coefficient ranged from 0.05 to 0.31. Rating challenges included assigning a single score for domains that may relate to both patients and care settings (that is, eligibility or recruitment) and determining to what extent aspects of complex research interventions differ from usual care. CONCLUSIONS: These five trials in diverse healthcare settings were rated as highly pragmatic using the PRECIS-2 criteria. Applying the tool generated insightful discussion about real-world design decisions but also highlighted challenges using the tool. PRECIS-2 raters would benefit from additional guidance about how to rate the interwoven patient and practice-level considerations that arise in pragmatic trials. TRIAL REGISTRATIONS: Clinicaltrials.gov trial registrations: NCT02019225 , NCT01742065 , NCT02015455 , NCT02113592 , NCT02063867 .

Unlocking the black box: supporting practices to become patient-centered medical homes.

BACKGROUND: Despite widespread interest in supporting primary care transformation, few evidence-based strategies for technical assistance exist. The Safety Net Medical Home Initiative (SNMHI) sought to develop a replicable and sustainable model for Patient-centered Medical Home practice transformation. OBJECTIVES: This paper describes the multimodal technical assistance approach used by the SNMHI and the participating practices' assessment of its value and helpfulness in supporting their transformation. RESULTS: Components of the technical assistance framework included: (1) individual site-level coaching provided by local medical home facilitators and supplemented by expert consultation; (2) regional and national learning communities of participating practices that included in-person meetings and field trips; (3) data monitoring and feedback including longitudinal feedback on medical home implementation as measured by the Patient-centered Medical Home-A; (4) written implementation guides, tools, and webinars relating to each of the 8 Change Concepts for Practice Transformation; and (5) small grant funds to support infrastructure and staff development. Overall, practices found the technical assistance helpful and most valued in-person, peer-to-peer-learning opportunities. Practices receiving technical assistance from membership organizations with which they belonged before the SNMHI scored higher on measures of medical home implementation than practices working with organizations with whom they had no prior relationship. CONCLUSIONS: There is an important role for both local and national organizations to provide nonduplicative, mutually reinforcing support for primary care transformation. How (in-person, between-peers) and by whom technical assistance is provided may be important to consider.

Development of a facilitation curriculum to support primary care transformation: the "coach medical home" curriculum.

BACKGROUND: In an effort to improve patient care, retain high-quality primary care providers, and control costs, primary care practices across the United States are transforming to patient-centered medical homes. This is no small task. Practice facilitation, also called "coaching," is increasingly being used to support system change; however, there is limited guidance for these programs. OBJECTIVE: To develop an evidence-based curriculum to help practice coaches guide broad-scale transformation efforts in primary care. METHODS: We gathered evidence about effective practice transformation coaching from 25 published programs and 8 expert interviews. Given limited published information, we drew extensively on our experience as leaders and coaches in the Safety Net Medical Home Initiative. Using these data, and with input from a User Group, we identified 6 curricular topics and created learning objectives and curricular content related to these topics. RESULTS: The Coach Medical Home curriculum guides coaches in the following areas: getting started with a practice; recognition and payment; sequencing changes; measurement; learning communities; and sustainability and spread. CONCLUSIONS: Coach Medical Home is a publically available web-based curriculum that provides tools, resources, and guidance for practice transformation support programs, including practice facilitators and learning community organizers.

Trends in elective labor induction for six United States health plans, 2001-2007.

BACKGROUND: To describe trends in labor induction, including elective induction, from 2001 to 2007 for six U.S. health plans and to examine the validity of induction measures derived from birth certificate and health plan data. METHODS: This retrospective cohort study included 339,123 deliveries at 35 weeks' gestation or greater. Linked health plan and birth certificate data provided information about induction, maternal medical conditions, and pregnancy complications. Induction was defined from diagnosis and procedure codes and birth certificate data and considered elective if no accepted indication was coded. We calculated induction prevalence across health plans and years. At four health plans, we reviewed medical records to validate induction measures. RESULTS: Based on electronic data, induction prevalence rose from 28% in 2001 to 32% in 2005, then declined to 29% in 2007. The trend was driven by changes in the prevalence of apparent elective induction, which rose from 11% in 2001 to 14% in 2005 and then declined to 11% in 2007. The trend was similar for subgroups by parity and gestational age. Elective induction prevalence varied considerably across plans. On review of 86 records, 36% of apparent elective inductions identified from electronic data were confirmed as valid. CONCLUSIONS: Elective induction appeared to peak in 2005 and then decline. The decrease may reflect quality improvement initiatives or changes in policies, patient or provider attitudes, or coding practices. The low validation rate for measures of elective induction defined from electronic data has important implications for existing quality measures and for research studies examining induction's outcomes.

A conceptual model of the role of complexity in the care of patients with multiple chronic conditions.

BACKGROUND: Effective healthcare for people with multiple chronic conditions (MCC) is a US priority, but the inherent complexity makes both research and delivery of care particularly challenging. As part of AHRQ Multiple Chronic Conditions Research Network (MCCRN) efforts, the Network developed a conceptual model to guide research in this area. OBJECTIVE: To synthesize methodological and topical issues relevant to MCC patient care into a framework that can improve the delivery of care and advance future research about caring for patients with MCC. METHODS: The Network synthesized essential constructs for MCC research identified from roundtable discussion, input from expert advisors, and previously published models. RESULTS: The AHRQ MCCRN conceptual model defines complexity as the gap between patient needs and healthcare services, taking into account both the multiple considerations that affect the needs of MCC patients, as well as the contextual factors that influence service delivery. The model reframes processes and outcomes to include not only clinical care quality and experience, but also patient health, well being, and quality of life. The single-condition paradigm for treating needs one-by-one falls apart and highlights the need for care systems to address dynamic patient needs. CONCLUSIONS: Defining complexity in terms of the misalignment between patient needs and services offers new insights in how to research and develop solutions to patient care needs.

How the provenance of electronic health record data matters for research: a case example using system mapping.

INTRODUCTION: The use of electronic health records (EHRs) for research is proceeding rapidly, driven by computational power, analytical techniques, and policy. However, EHR-based research is limited by the complexity of EHR data and a lack of understanding about data provenance, meaning the context under which the data were collected. This paper presents system flow mapping as a method to help researchers more fully understand the provenance of their EHR data as it relates to local workflow. We provide two specific examples of how this method can improve data identification, documentation, and processing. BACKGROUND: EHRs store clinical and administrative data, often in unstructured fields. Each clinical system has a unique and dynamic workflow, as well as an EHR customized for local use. The EHR customization may be influenced by a broader context such as documentation required for billing. METHODS: We present a case study with two examples of using system flow mapping to characterize EHR data for a local colorectal cancer screening process. FINDINGS: System flow mapping demonstrated that information entered into the EHR during clinical practice required interpretation and transformation before it could be accurately applied to research. We illustrate how system flow mapping shaped our knowledge of the quality and completeness of data in two examples: (1) determining colonoscopy indication as recorded in the EHR, and (2) discovering a specific EHR form that captured family history. DISCUSSION: Researchers who do not consider data provenance risk compiling data that are systematically incomplete or incorrect. For example, researchers who are not familiar with the clinical workflow under which data were entered might miss or misunderstand patient information or procedure and diagnostic codes. CONCLUSIONS: Data provenance is a fundamental characteristic of research data from EHRs. Given the diversity of EHR platforms and system workflows, researchers need tools for evaluating and reporting data availability, quality, and transformations. Our case study illustrates how system mapping can inform researchers about the provenance of their data as it pertains to local workflows.

Methods of linking mothers and infants using health plan data for studies of pregnancy outcomes.

PURPOSE: Research on medication safety in pregnancy often utilizes health plan and birth certificate records. This study discusses methods used to link mothers with infants, a crucial step in such research. METHODS: We describe how eight sites participating in the Medication Exposure in Pregnancy Risk Evaluation Program created linkages between deliveries, infants and birth certificates for the 2001-2007 birth cohorts. We describe linkage rates across sites, and for two sites, we compare the characteristics of populations linked using different methods. RESULTS: Of 299,260 deliveries, 256,563 (86%; range by site, 74-99%) could be linked to infants using a deterministic algorithm. At two sites, using birth certificate data to augment mother-infant linkage increased the representation of mothers who were Hispanic or non-White, younger, Medicaid recipients, or had low educational level. A total of 236,460 (92%; range by site, 82-100%) deliveries could be linked to a birth certificate. CONCLUSIONS: Tailored approaches enabled linking most deliveries to infants and to birth certificates, even when data systems differed. The methods used may affect the composition of the population identified. Linkages established with such methods can support sound pharmacoepidemiology studies of maternal drug exposure outside the context of a formal registry.

Validation of an algorithm to estimate gestational age in electronic health plan databases.

PURPOSE: To validate an algorithm that uses delivery date and diagnosis codes to define gestational age at birth in electronic health plan databases. METHODS: Using data from 225,384 live born deliveries to women aged 15-45 years in 2001-2007 within eight of the 11 health plans participating in the Medication Exposure in Pregnancy Risk Evaluation Program, we compared (1) the algorithm-derived gestational age versus the "gold-standard" gestational age obtained from the infant birth certificate file and (2) the prenatal exposure status of two antidepressants (fluoxetine and sertraline) and two antibiotics (amoxicillin and azithromycin) as determined by the algorithm-derived versus the gold-standard gestational age. RESULTS: The mean algorithm-derived gestational age at birth was lower than the mean obtained from the birth certificate file among singleton deliveries (267.9 vs 273.5 days) but not among multiple-gestation deliveries (253.9 vs 252.6 days). The algorithm-derived prenatal exposure to the antidepressants had a sensitivity and a positive predictive value of ≥95%, and a specificity and a negative predictive value of almost 100%. Sensitivity and positive predictive value were both ≥90%, and specificity and negative predictive value were both >99% for the antibiotics. CONCLUSIONS: A gestational age algorithm based upon electronic health plan data correctly classified medication exposure status in most live born deliveries, but trimester-specific misclassification may be higher for drugs typically used for short durations.

Interest in an online smoking cessation program and effective recruitment strategies: results from Project Quit.

BACKGROUND: The Internet is a promising venue for delivering smoking cessation treatment, either as a stand-alone program or as an adjunct to pharmacotherapy. However, there is little data to indicate what percent of smokers are interested in receiving online smoking cessation services or how best to recruit smokers to Internet-based programs. OBJECTIVE: Using a defined recruitment sample, this study aimed to identify the percentage of smokers who expressed interest in or enrolled in Project Quit, a tailored, online, cognitive-behavioral support program offered with adjunctive nicotine replacement therapy patches. In addition, we examined the effectiveness of several individual-level versus population-level recruitment strategies. METHODS: Members from two large health care organizations in the United States were invited to participate in Project Quit. Recruitment efforts included proactive invitation letters mailed to 34533 likely smokers and reactive population-level study advertisements targeted to all health plan members (> 560000 adults, including an estimated 98000 smokers across both health care organizations). RESULTS: An estimated 1.6% and 2.5% of adult smokers from each health care organization enrolled in Project Quit. Among likely smokers who received proactive study invitations, 7% visited the Project Quit website (n = 2260) and 4% (n = 1273) were eligible and enrolled. Response rates were similar across sites, despite using different sources to assemble the invitation mailing list. Proactive individual-level recruitment was more effective than other forms of recruitment, accounting for 69% of website visitors and 68% of enrollees. CONCLUSIONS: Smokers were interested in receiving online smoking cessation support, even though they had access to other forms of treatment through their health insurance. Uptake rates for this program were comparable to those seen when smokers are advised to quit and are referred to other forms of smoking cessation treatment. In this sample, proactive mailings were the best method for recruiting smokers to Project Quit.

The coordinated clinical studies network: a multidisciplinary alliance to facilitate research and improve care.

The NIH Roadmap is a major effort to reshape the US health research enterprise to accelerate medical discovery and to do so in such a way that actually hastens population health improvement through research. The Roadmap's ultimate goal resonates with the HMO Research Network, a consortium of integrated health care systems that uses its collective scientific capabilities to integrate research, practice, and policy for the improvement of health and health care among diverse populations. (See page 6 for abstracts from the HMO Research Network annual conference.) As such, the HMO Research Network was ideally suited to propose a new consortium project as a part of the NIH Roadmap, the Coordinated Clinical Studies Network (CCSN). The CCSN was funded in 2004 to create a path-breaking research facility that leverages several distinctive features of the HMO Research Network: the multidisciplinary scientific capabilities of its researchers; the ability to rapidly move clinical research findings into care delivery; its large, diverse patient populations; and a commitment to placing its findings in the public domain. Among the goals of the CCSN are to augment the capacity and infrastructure for conducting research, and to use considerable investments in health informatics to improve the scope and efficiency of research data collection. The NIH Roadmap is a revolutionary step toward a new paradigm for research and responds to both a compelling social need and rapid technological advances in biomedicine. The CCSN's participation in the Roadmap Initiative is a unique opportunity for researchers, clinicians, and our patients.

The migration of physicians from sub-Saharan Africa to the United States of America: measures of the African brain drain.

BACKGROUND: The objective of this paper is to describe the numbers, characteristics, and trends in the migration to the United States of physicians trained in sub-Saharan Africa. METHODS: We used the American Medical Association 2002 Masterfile to identify and describe physicians who received their medical training in sub-Saharan Africa and are currently practicing in the USA. RESULTS: More than 23% of America's 771 491 physicians received their medical training outside the USA, the majority (64%) in low-income or lower middle-income countries. A total of 5334 physicians from sub-Saharan Africa are in that group, a number that represents more than 6% of the physicians practicing in sub-Saharan Africa now. Nearly 86% of these Africans practicing in the USA originate from only three countries: Nigeria, South Africa and Ghana. Furthermore, 79% were trained at only 10 medical schools. CONCLUSIONS: Physician migration from poor countries to rich ones contributes to worldwide health workforce imbalances that may be detrimental to the health systems of source countries. The migration of over 5000 doctors from sub-Saharan Africa to the USA has had a significantly negative effect on the doctor-to-population ratio of Africa. The finding that the bulk of migration occurs from only a few countries and medical schools suggests policy interventions in only a few locations could be effective in stemming the brain drain.

Developing local public health capacity in cultural competency: a case study with Haitians in a rural community.

With the increase in cultural diversity in all regions of the United States, public health employees and other health care providers are more challenged than ever before to provide culturally sensitive care to citizens from an increasing range of cultures. Building on their existing experience and skill, health care staff must expand their competencies to address this changing diversity in their communities. This project serves as a case study of how 1 small rural health department in Delaware created a Web site using Purnell's model for cultural competence (Purnell & Paulanka, 2003) as the organizational framework and rose to the challenge of assisting public health staff to provide culturally sensitive health services to a rapidly increasing population of Haitian immigrants.

Gender-related factors in the recruitment of physicians to the rural Northwest.

BACKGROUND: This study examines differences in the factors female and male physicians considered influential in their rural practice location choice and describes the practice arrangements that successfully recruited female physicians to rural areas. METHODS: This cross-sectional study was based on a mailed survey of physicians successfully recruited between 1992 and 1999 to towns of 10,000 or less in six states in the Pacific Northwest. RESULTS: Responses from 77 men and 37 women (response rate 61%) indicated that women were more likely than men to have been influenced in making their practice choice by issues related to spouse or personal partner, flexible scheduling, family leave, availability of childcare, and the interpersonal aspects of recruitment. Commonly reported themes reflected the respondents' desire for flexibility regarding family issues and the value they placed on honesty during recruitment. CONCLUSIONS: It is very important in recruitment of both men and women to highlight the positive aspects of the community and to involve and assist the physician's spouse or partner. If they want to achieve a gender-balanced physician workforce, rural communities and practices recruiting physicians should place high priority on practice scheduling, spouse-partner, and interpersonal issues in the recruitment process.