Palo Alto Medical Foundation

Recently there has been a remarkable upsurge in activity surrounding the adoption of personal health record (PHR) systems for patients and consumers. The biomedical literature does not yet adequately describe the potential capabilities and utility of PHR systems. In addition, the lack of a proven business case for widespread deployment hinders PHR adoption. In a 2005 working symposium, the American Medical Informatics Association's College of Medical Informatics discussed the issues surrounding personal health record systems and developed recommendations for PHR-promoting activities. Personal health record systems are more than just static repositories for patient data; they combine data, knowledge, and software tools, which help patients to become active participants in their own care. When PHRs are integrated with electronic health record systems, they provide greater benefits than would stand-alone systems for consumers. This paper summarizes the College Symposium discussions on PHR systems and provides definitions, system characteristics, technical architectures, benefits, barriers to adoption, and strategies for increasing adoption.

Although many clinicians feel they already use shared decision making, research shows a perception-reality gap. A M Stiggelbout and colleagues discuss why it is important and highlight some best practices.

RATIONALE: Poor adherence to asthma controller medications results in poor treatment outcomes. OBJECTIVES: To compare controller medication adherence and clinical outcomes in 612 adults with poorly controlled asthma randomized to one of two different treatment decision-making models or to usual care. METHODS: In shared decision making (SDM), nonphysician clinicians and patients negotiated a treatment regimen that accommodated patient goals and preferences. In clinician decision making, treatment was prescribed without specifically eliciting patient goals/preferences. The otherwise identical intervention protocols both provided asthma education and involved two in-person and three brief phone encounters. MEASUREMENTS AND MAIN RESULTS: Refill adherence was measured using continuous medication acquisition (CMA) indices-the total days' supply acquired per year divided by 365 days. Cumulative controller medication dose was measured in beclomethasone canister equivalents. In follow-up Year 1, compared with usual care, SDM resulted in: significantly better controller adherence (CMA, 0.67 vs. 0.46; P < 0.0001) and long-acting beta-agonist adherence (CMA, 0.51 vs. 0.40; P = 0.0225); higher cumulative controller medication dose (canister equivalent, 10.9 vs. 5.2; P < 0.0001); significantly better clinical outcomes (asthma-related quality of life, health care use, rescue medication use, asthma control, and lung function). In Year 2, compared with usual care, SDM resulted in significantly lower rescue medication use, the sole clinical outcome available for that year. Compared with clinician decision making, SDM resulted in: significantly better controller adherence (CMA, 0.67 vs. 0.59; P = 0.03) and long-acting beta-agonist adherence (CMA, 0.51 vs. 0.41; P = 0.0143); higher cumulative controller dose (CMA, 10.9 vs. 9.1; P = 0.005); and quantitatively, but not significantly, better outcomes on all clinical measures. CONCLUSIONS: Negotiating patients' treatment decisions significantly improves adherence to asthma pharmacotherapy and clinical outcomes. Clinical trials registered with www.clinicaltrials.gov (NCT00217945 and NCT00149526).

BACKGROUND: Toxoplasmosis can cause severe ocular and neurological disease. We sought to determine risk factors for Toxoplasma gondii infection in the United States. METHODS: We conducted a case-control study of adults recently infected with T. gondii. Case patients were selected from the Palo Alto Medical Foundation Toxoplasma Serology Laboratory from August 2002 through May 2007; control patients were randomly selected from among T. gondii-seronegative persons. Data were obtained from serological testing and patient questionnaires. RESULTS: We evaluated 148 case patients with recent T. gondii infection and 413 control patients. In multivariate analysis, an elevated risk of recent T. gondii infection was associated with the following factors: eating raw ground beef (adjusted odds ratio [aOR], 6.67; 95% confidence limits [CLs], 2.09, 21.24; attributable risk [AR], 7%); eating rare lamb (aOR, 8.39; 95% CLs, 3.68, 19.16; AR, 20%); eating locally produced cured, dried, or smoked meat (aOR, 1.97; 95% CLs, 1.18, 3.28; AR, 22%); working with meat (aOR, 3.15; 95% CLs, 1.09, 9.10; AR, 5%); drinking unpasteurized goat's milk (aOR, 5.09; 95% CLs, 1.45, 17.80; AR, 4%); and having 3 or more kittens (aOR, 27.89; 95% CLs, 5.72, 135.86; AR, 10%). Eating raw oysters, clams, or mussels (aOR, 2.22; 95% CLs, 1.07, 4.61; AR, 16%) was significant in a separate model among persons asked this question. Subgroup results are also provided for women and for pregnant women. CONCLUSIONS: In the United States, exposure to certain raw or undercooked foods and exposure to kittens are risk factors for T. gondii infection. Knowledge of these risk factors will help to target prevention efforts.

BACKGROUND: Integrated personal health records (PHRs) offer significant potential to stimulate transformational changes in health care delivery and self-care by patients. In 2006, an invitational roundtable sponsored by Kaiser Permanente Institute, the American Medical Informatics Association, and the Agency for Healthcare Research and Quality was held to identify the transformative potential of PHRs, as well as barriers to realizing this potential and a framework for action to move them closer to the health care mainstream. This paper highlights and builds on the insights shared during the roundtable. DISCUSSION: While there is a spectrum of dominant PHR models, (standalone, tethered, integrated), the authors state that only the integrated model has true transformative potential to strengthen consumers' ability to manage their own health care. Integrated PHRs improve the quality, completeness, depth, and accessibility of health information provided by patients; enable facile communication between patients and providers; provide access to health knowledge for patients; ensure portability of medical records and other personal health information; and incorporate auto-population of content. Numerous factors impede widespread adoption of integrated PHRs: obstacles in the health care system/culture; issues of consumer confidence and trust; lack of technical standards for interoperability; lack of HIT infrastructure; the digital divide; uncertain value realization/ROI; and uncertain market demand. Recent efforts have led to progress on standards for integrated PHRs, and government agencies and private companies are offering different models to consumers, but substantial obstacles remain to be addressed. Immediate steps to advance integrated PHRs should include sharing existing knowledge and expanding knowledge about them, building on existing efforts, and continuing dialogue among public and private sector stakeholders. SUMMARY: Integrated PHRs promote active, ongoing patient collaboration in care delivery and decision making. With some exceptions, however, the integrated PHR model is still a theoretical framework for consumer-centric health care. The authors pose questions that need to be answered so that the field can move forward to realize the potential of integrated PHRs. How can integrated PHRs be moved from concept to practical application? Would a coordinating body expedite this progress? How can existing initiatives and policy levers serve as catalysts to advance integrated PHRs?

Patient-centered care requires different approaches depending on the clinical situation. Motivational interviewing and shared decision making provide practical and well-described methods to accomplish patient-centered care in the context of situations where medical evidence supports specific behavior changes and the most appropriate action is dependent on the patient's preferences. Many clinical consultations may require elements of both approaches, however. This article describes these 2 approaches-one to address ambivalence to medically indicated behavior change and the other to support patients in making health care decisions in cases where there is more than one reasonable option-and discusses how clinicians can draw on these approaches alone and in combination to achieve patient-centered care across the range of health care problems.

BACKGROUND: There is increasing interest in interventions that can support patients who face difficult decisions and individuals who need to modify their behaviour to achieve better outcomes. Evidence for effectiveness is used to categorize patients care. Effective care is where evidence of benefit outweighs harm: patients should always receive this type of care, where indicated. Preference-sensitive care describes a situation where the evidence for the superiority of one treatment over another is either not available or does not allow differentiation; in this situation, there are two or more valid approaches, and the best choice depends on how individuals value the risks and benefits of treatments. DISCUSSION: Preference-sensitive decisions are defined by equipoise: situations where options need to be deliberated. Moreover, where both healthcare professionals and patients agree that equipoise exists, situations may be regarded as having 'dual equipoise'. Such conditions are ideal for shared decision making. However, there are many situations in medicine where dual equipoise does not exist, where health professionals hold the view that scientific evidence for benefit strongly outweighs harm. This is often the case where people suffer from chronic conditions, and where behaviour change is recommended to improve outcomes. However, some patients, are either ambivalent or find it difficult to sustain optimal behaviours, i.e., patients will be in varying degrees of equipoise. Therefore, situations where dual equipoise exists (or not) help to clarify the definitions of two classes of support, namely, decision and behaviour change support interventions. Decision support interventions help people think about choices they face; they describe where and why choice exists, in short, conditions of dual equipoise; they provide information about options, including, where reasonable, the option of taking no action. These interventions help people to deliberate, independently or in collaboration with others, about options by considering relevant attributes; they support people to forecast how they might feel about short, intermediate, and long-term outcomes that have relevant consequences, in ways that help the process of constructing preferences and eventual decision making appropriate to their individual situation. Whereas, behavioural support interventions describe, justify, and recommend actions that, over time, lead to predictable outcomes over short, intermediate, and long-term timeframes, and that have relevant and important consequences for those who are considering behaviour change. SUMMARY: Decision and behaviour support interventions have divergent aims, different relationships to equipoise, and form two classes of interventions.

Widespread adoption of information technology is now regarded as a pathway to improving health care and achieving the Institute of Medicine's highly regarded six aims for redesigning care. Achieving these aims requires fresh approaches to health system design, including continuous healing relationships between physicians and patients and provision of tools to help patients be more active participants in their own care. Personal health records (PHRs) might allow patients and providers to develop new ways of collaborating and provide the basis for broader transformation of the health care system. Federal policies can be key catalysts in accelerating PHR development and adoption.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a debilitating lung disease with a survival of only three to five years from the time of diagnosis. Due to a paucity of studies, large gaps remain in our understanding of how IPF affects the quality of patients' lives. In only one other study did investigators ask patients directly for their perspectives on this topic. Further, currently there is no disease-specific instrument to measure health-related quality of life (HRQL) in patients with IPF. A carefully constructed measurement instrument, sensitive to underlying change, is needed for use in clinical trials and longitudinal studies of patients with IPF. Before developing such an instrument, researchers must improve their understanding of the relevant effects of IPF on patients' lives. On a broader scale, to provide the best care for people with IPF, clinicians must appreciate--from patients' perspectives--how this disease affects various aspects of their lives. METHODS: We used focus groups and individual in-depth interviews with 20 IPF patients to collect their perspectives on how IPF affects their lives (with a focus on the quality of their lives). We then analyzed these perspectives and organized them into a conceptual framework for describing HRQL in patients with IPF. Next, we examined how well certain existing measurement instruments--which have been administered to IPF patients in prior studies--covered the domains and topics our patients identified. RESULTS: In our framework, we identified 12 primary domains: symptoms, IPF therapy, sleep, exhaustion, forethought, employment and finances, dependence, family, sexual relations, social participation, mental and spiritual well-being, mortality. Each domain is composed of several topics, which describe how IPF affects patients' lives. When we compared the content of our conceptual framework with the existing instruments, we found the coverage of the existing instruments to be inadequate for several reasons, including they may tap general areas of QOL or HRQL but not some areas that appear to be most directly affected by IPF, and they include items that are relevant to symptoms and effects of other respiratory diseases but not IPF. CONCLUSION: Collecting patients' perspectives and developing an organized inventory of the relevant effects of IPF on patients' lives provides valuable information for improving our understanding of the impact of this disease on patients and their loved ones. We believe our findings will help alert clinicians and researchers to IPF patients' experiences and concerns. Based on the comparison or our conceptual framework with the content of four existing instruments, it would appear that developing an IPF-specific measurement instrument is justified. Our conceptual framework for describing health-related quality of life in patients with IPF lays a solid foundation for constructing such an instrument.

OBJECTIVE: To standardize the recording of surgical phenotypic information on endometriosis and related sample collections obtained at laparoscopy, allowing large-scale collaborative research into the condition. DESIGN: An international collaboration involving 34 clinical/academic centers and three industry collaborators from 16 countries. SETTING: Two workshops were conducted in 2013, bringing together 54 clinical, academic, and industry leaders in endometriosis research and management worldwide. PATIENT(S): None. INTERVENTION(S): A postsurgical scoring sheet containing general and gynecological patient and procedural information, extent of disease, the location and type of endometriotic lesion, and any other findings was developed during several rounds of review. Comments and any systematic surgical data collection tools used in the reviewers' centers were incorporated. MAIN OUTCOME MEASURE(S): The development of a standard recommended (SSF) and minimum required (MSF) form to collect data on the surgical phenotype of endometriosis. RESULT(S): SSF and MSF include detailed descriptions of lesions, modes of procedures and sample collection, comorbidities, and potential residual disease at the end of surgery, along with previously published instruments such as the revised American Society for Reproductive Medicine and Endometriosis Fertility Index classification tools for comparison and validation. CONCLUSION(S): This is the first multicenter, international collaboration between academic centers and industry addressing standardization of phenotypic data collection for a specific disease. The Endometriosis Phenome and Biobanking Harmonisation Project SSF and MSF are essential tools to increase our understanding of the pathogenesis of endometriosis by allowing large-scale collaborative research into the condition.

BACKGROUND: Asian Americans (AA) are the fastest growing U.S. population, and when properly distinguished by their ethnic origins, exhibit substantial heterogeneity in socioeconomic status, health behaviors, and health outcomes. Cancer is the second leading cause of death in the United States, yet trends and current patterns in the mortality burden of cancer among AA ethnic groups have not been documented. METHODS: We report age-adjusted rates, standardized mortality ratios, and modeled trends in cancer-related mortality in the following AA ethnicities: Asian Indians, Chinese, Filipinos, Japanese, Koreans, and Vietnamese, from 2003 to 2011, with non-Hispanic whites (NHW) as the reference population. RESULTS: For most cancer sites, AAs had lower cancer mortality than NHWs; however, mortality patterns were heterogeneous across AA ethnicities. Stomach and liver cancer mortality was very high, particularly among Chinese, Koreans, and Vietnamese, for whom these two cancer types combined accounted for 15% to 25% of cancer deaths, but less than 5% of cancer deaths in NHWs. In AA women, lung cancer was a leading cause of death, but (unlike males and NHW females) rates did not decline over the study period. CONCLUSIONS: Ethnicity-specific analyses are critical to understanding the national burden of cancer among the heterogeneous AA population. IMPACT: Our findings highlight the need for disaggregated reporting of cancer statistics in AAs and warrant consideration of tailored screening programs for liver and gastric cancers. Cancer Epidemiol Biomarkers Prev; 25(10); 1371-82. ©2016 AACR.

Toxoplasmic retinochoroiditis is deemed a local event, which may fail to evoke a detectable systemic immune response. A correct diagnosis of the disease is a necessary basis for estimating its clinical burden. This is not so difficult in a typical clinical picture. In atypical cases, further diagnostic efforts are to be installed. Although the aqueous humor may be analyzed for specific antibodies or the presence of parasitic DNA, the DNA burden therein is low, and in rare instances a confirmation would necessitate vitreous sampling. A laboratory confirmation of the diagnosis is frustrated by individual differences in the time elapsing between clinical symptoms and activation of specific antibody production, which may result in false negatives. In congenital ocular toxoplasmosis, a delay in the onset of specific local antibody production could reflect immune tolerance. Herein, the authors attempt to provide a simple and practicable algorithm for a clinically tailored diagnostic approach in atypical instances.

A positive Toxoplasma immunoglobulin M (IgM) result is often interpreted as a marker of an acute infection. However, IgM can persist for several years, and Toxoplasma commercial IgM diagnostic test kits can yield a number of false-positive results. For these reasons, a chronic Toxoplasma infection can be erroneously classified as an acute infection, resulting in serious adverse consequences, especially in pregnant women, leading to emotional distress and unnecessary interventions, including termination of pregnancy. Interpretation of Toxoplasma serology at a reference laboratory can help differentiate a recently acquired infection from a chronic infection. Serological test results for 451 patients with positive Toxoplasma IgM and IgG test results obtained at nonreference laboratories (NRLs) that were referred to Palo Alto Medical Foundation Toxoplasma Serology Laboratory (PAMF-TSL) to determine whether the patient was acutely or chronically infected were retrospectively reviewed. PAMF-TSL results established that of the 451 patients, 335 (74%) had a chronic infection, 100 (22%) had an acute infection, and 7 (2%) were not infected, and for 9 (2%), results were indeterminate. Positive Toxoplasma IgM and IgG test results obtained at NRLs cannot accurately distinguish between acute and chronic infections. To do so, testing at reference laboratories is required, as mandated in 1997 in a letter from the Food and Drug Administration (FDA) to clinicians and laboratories in the United States.

BACKGROUND: Navicular stress fractures of the foot often are difficult to diagnose and treat. METHODS: Nineteen athletic patients seen from 1999 to 2003, were compared to a previously treated group of 22 athletes with similar injuries treated from 1994 to 1998. Based on the frontal plane CT images, a previously described classification system was used to assess the injury: type I dorsal cortical break; type II fracture extending into the navicular body; and type III fracture breaches two cortices. Nonoperative treatment was recommended for patients with type I injuries and open reduction and internal fixation (ORIF) were recommended for those with type II and III injuries. The time to return to activity and ability to return to competition were assessed, along with differences between fracture type and gender. RESULTS: Return to activity (RTA) was 4.0 months for the entire group. RTA for type I (four injuries), type II (eight injuries), and type III (seven injuries) was 3.8, 3.7, and 4.2 months, respectively. Fifteen of 16 competitive athletes returned to full competition, including all who had ORIF. CONCLUSIONS: Navicular stress fractures can take 4 months to heal with nonoperative or operative treatment. Surgery should be considered for more severe injuries, which can be assessed by CT scan.

BACKGROUND: Recent research has shown that neighborhood characteristics are associated with obesity prevalence. While food advertising in periodicals and television has been linked to overweight and obesity, it is unknown whether outdoor advertising is related to obesity. METHODS: To test the association between outdoor food advertising and obesity, we analyzed telephone survey data on adults, aged 18-98, collected from 220 census tracts in Los Angeles and Louisiana. We linked self-reported information on BMI and soda consumption with a database of directly observed outdoor advertisements. RESULTS: The higher the percentage of outdoor advertisements promoting food or non-alcoholic beverages within a census tract, the greater the odds of obesity among its residents, controlling for age, race and educational status. For every 10% increase in food advertising, there was a 1.05 (95% CI 1.003 - 1.093, p<0.03) greater odds of being overweight or obese, controlling for other factors. Given these predictions, compared to an individual living in an area with no food ads, those living in areas in which 30% of ads were for food would have a 2.6% increase in the probability of being obese. CONCLUSIONS: There is a relationship between the percentage of outdoor food advertising and overweight/obesity.

Endothelial lipase (EL) is a newly described member of the triglyceride lipase gene family. It has a considerable molecular homology with lipoprotein lipase (LPL) (44%) and hepatic lipase (HL) (41%). Unlike LPL and HL, this enzyme is synthesized by endothelial cells and functions at the site where it is synthesized. Furthermore, its tissue distribution is different from that of LPL and HL. As a lipase, EL has primarily phospholipase A1 activity. Animals that overexpress EL showed reduced HDL cholesterol levels. Conversely, animals that are deficient in EL showed a marked elevation in HDL cholesterol levels, suggesting that it plays a physiologic role in HDL metabolism. Unlike LPL and HL, EL is located in the vascular endothelial cells and its expression is highly regulated by cytokines and physical forces, suggesting that it may play a role in the development of atherosclerosis. However, there is only a limited amount of information available about this enzyme.Some of our unpublished data in addition to previously published data support the possibility that the enzyme plays a role in the formation of atherosclerotic lesion. Endothelial lipase (EL) is a newly described member of the triglyceride lipase gene family. It has a considerable molecular homology with lipoprotein lipase (LPL) (44%) and hepatic lipase (HL) (41%). Unlike LPL and HL, this enzyme is synthesized by endothelial cells and functions at the site where it is synthesized. Furthermore, its tissue distribution is different from that of LPL and HL. As a lipase, EL has primarily phospholipase A1 activity. Animals that overexpress EL showed reduced HDL cholesterol levels. Conversely, animals that are deficient in EL showed a marked elevation in HDL cholesterol levels, suggesting that it plays a physiologic role in HDL metabolism. Unlike LPL and HL, EL is located in the vascular endothelial cells and its expression is highly regulated by cytokines and physical forces, suggesting that it may play a role in the development of atherosclerosis. However, there is only a limited amount of information available about this enzyme. Some of our unpublished data in addition to previously published data support the possibility that the enzyme plays a role in the formation of atherosclerotic lesion. Lipid esters provide a means of allowing the storage and transport of a large variety of molecules of nutritional and biologic importance. However, the hydrophobicity of these compounds requires that they be modified before the constituent fatty acids can be transported across membranes or used for energy. Thus, a series of synthases and lipases have evolved for the purpose of assembling and disassembling lipid esters. Pancreatic lipase was the first triglyceride lipase characterized. When molecular studies revealed its homology to lipoprotein lipase (LPL) and hepatic lipase (HL) (1Ben-Aviram C.N. Ben-Zeev O. Lee R.D. Haaga K. Shively J.E. Goers J.W. Pedersen M.E. Reeve Jr., J.R. Schotz M.C. Homology of lipoprotein lipase to pancreatic lipase.Proc. Natl. Acad. Sci. USA. 1986; 83: 4185-4189Google Scholar, 2Ben-Zeev O. Ben-Aviramn C.M. Wong H. Nikazy J. Shively J.E. Schotz M.C. Hepatic lipase: a member of a family of structurally related lipases.Biochim. Biophs. Acta. 1987; 919: 13-20Google Scholar, 3Kirchgessner T.G. Chuat J-C. Heinzmann C. Etienne J. Guilhot S. Svenson K. Ameis D. Pilon C. D'Auriol L. Andalibi A. Schotz M.C. Galivert F. Lusis A.J. Organization of the human lipoprotein lipase gene and evolution of the lipase gene family.Proc. Natl. Acad. Sci. USA. 1989; 86: 9647-9651Google Scholar, 4Hide W.A. Chan L. Li W-H. Structure and evolution of the lipase superfamily.J. Lipid Res. 1992; 33: 167-177Google Scholar) it might have been assumed that this family would consist of enzymes that hydrolyzed triglycerides as their primary substrate (5Lowe M.E. Molecular mechanisms of rat and human pancreatic triglyceride lipases.J. Nutr. 1997; 127: 549-557Google Scholar, 6Olivecrona T. Bengtsson-Olivecrona G. Lipoprotein lipase and hepatic lipase.Curr. Opin. Lipidol. 1993; 4: 187-196Google Scholar). The discovery of pancreatic lipase-related protein 2 further supported this possibility (7Lowe M.E. Properties and function of pancreatic lipase related protein 2.Biochimie. 2000; 82: 997-1004Google Scholar). More recently, the discovery of a homologous enzyme that has phosphatidylserine as its primary substrate (8Sato T. Aoki J. Nagai Y. Dohmae N. Takio K. Takefumi D. Hiroyuki A. Inoue K. Serine phospholipid-specific phospholipase A that is secreted from activated platelets.J. Biol. Chem. 1997; 272: 2192-2198Google Scholar), however, was inconsistent with this notion. The enzyme that is the subject of this review endothelial lipase (EL), also has almost exclusively phospholipase activity (9Jaye M. Lunch K.J. Krawiec J. Marchadier D. Maugeais C. Doan K. South V. Amin D. Perrone M. Rader D.J. A novel endothelial-derived lipase that modulates HDL metabolism.Nat. Genet. 1999; 21: 424-428Google Scholar, 10Hirata K. Dichek H.L. Cioffi J.A. Choi S.Y. Leeper N.J. Quintana L. Kronmal G.S. Cooper A.D. Quertermous T. Cloning of a unique lipase from endothelial cells extends the lipase gene family.J. Biol. Chem. 1999; 274: 14170-14175Google Scholar) and most recently a phosphatidic acid selective phospholipase A1 that was found by a homology search of the phosphatidylserine esterase has been described (11Sonoda H. Aoki J. Hiramatsu T. Ishida M. Bandoh K. Nagai Y. Taguchi R. Inoue K. Arai H. A novel phosphatidic acid-selective phospholipase A1 that produces lysophosphatidic acid.J. Biol. Chem. 2002; 277: 34254-34263Google Scholar). Thus, the family should be thought of as glycerol-sn-1-fatty acid hydrolases. Remarkable about the enzymes is their disparate and relatively organ specific locations, which suggests that they may have evolved to play relatively specific roles in the metabolism of a particular organ. In addition to contribution to lipid metabolism in a particular organ, two of the enzymes, LPL and HL, have been proven to affect lipoprotein levels and distribution among classes. EL has now potentially joined this group. The presence of EL on the endothelium lining blood vessels in numerous organs, its presence in macrophages, and the report that its transcription is induced by inflammatory signals (12Hirata K. Ishida T. Matsushita H. Tsao P.S. Quertermous T. Regulated expression of endothelial cell-derived lipase.Biochem. Biophys. Res. Commun. 2000; 272: 90-93Google Scholar) raises the possibility that this enzyme may play a role in the response of the vascular wall to injury and thus plays a direct role in the formation of atherosclerotic lesions. Although currently there is a limited amount of information about the enzyme, it is likely that a great deal more will be learned in the near future. EL was cloned by two groups using similar methodologies but addressing very different biological questions. Our group employed suppression subtraction hybridization to characterize the genetic basis for endothelial cell mediated vascular formation (10Hirata K. Dichek H.L. Cioffi J.A. Choi S.Y. Leeper N.J. Quintana L. Kronmal G.S. Cooper A.D. Quertermous T. Cloning of a unique lipase from endothelial cells extends the lipase gene family.J. Biol. Chem. 1999; 274: 14170-14175Google Scholar). Cultured human umbilical vein endothelial cells (HUVEC) were employed in an in vitro model of tube development on The was to that were by tube to in this were by and two to a novel of the expression of this gene tube formation was by Cloning of the primary human was by a and the highly homologous was and from a (10Hirata K. Dichek H.L. Cioffi J.A. Choi S.Y. Leeper N.J. Quintana L. Kronmal G.S. Cooper A.D. Quertermous T. Cloning of a unique lipase from endothelial cells extends the lipase gene family.J. Biol. Chem. 1999; 274: 14170-14175Google Scholar). A group cloned the gene using to that were regulated in cells by (9Jaye M. Lunch K.J. Krawiec J. Marchadier D. Maugeais C. Doan K. South V. Amin D. Perrone M. Rader D.J. A novel endothelial-derived lipase that modulates HDL metabolism.Nat. Genet. 1999; 21: 424-428Google Scholar). in vitro model was cells that were by with cells were to or and for and by were on a and and in the and by of the human was by of and of a human of the primary of the human and EL to the primary of lipases considerable of suggesting of EL was to be to human LPL and to human HL, with considerable of The human and EL were to have a and thus to be secreted in with function of the similar LPL and of the was to in acid human and lipase with the human LPL and acid revealed of the acid and as as the in formation H. A. C. Lipoprotein Molecular model on the pancreatic lipase for and Biol. Chem. Scholar). two of acids and that are to the and are also of these is they are to be for lipase with the lipid LPL and that are for substrate with the of LPL and HL, EL has a that a and to substrate for EL Dichek H.L. S. hepatic and lipoprotein lipase: the the site lipase substrate Biol. Chem. Scholar, A. Structure of human pancreatic Scholar). the EL has homology with the LPL and it was assumed from the that EL would have different substrate from the the in the EL showed of to LPL and in the the In with the human LPL of in H. A. C. Lipoprotein Molecular model on the pancreatic lipase for and Biol. Chem. Scholar). The in EL and 4: are by the presence of the at and may the of is for at EL that from protein of protein synthesized and secreted by and human endothelial cells was with a a acids of the secreted protein (9Jaye M. Lunch K.J. Krawiec J. Marchadier D. Maugeais C. Doan K. South V. Amin D. Perrone M. Rader D.J. A novel endothelial-derived lipase that modulates HDL metabolism.Nat. Genet. 1999; 21: 424-428Google Scholar). studies of and the of with the molecular of the this was to the of the enzyme. The large was to the primary on their of the it was that it most likely a protein of the was supported by expression in cells a thus the possibility of as a a of the protein would have a very different from the the will be to these and studies of the protein in will provide the biological functions of this of EL is also at the genetic by in and by in of the for different was first that were at EL by activated endothelial cells (12Hirata K. Ishida T. Matsushita H. Tsao P.S. Quertermous T. Regulated expression of endothelial cell-derived lipase.Biochem. Biophys. Res. Commun. 2000; 272: 90-93Google Scholar). these a unique was unpublished Although this is similar at the to the previously described and the of it an A that as an in the described as an and a EL protein by of the the novel protein that would be in this would have a and thus would be to be secreted from the this protein is in and that it is secreted has been in cells unpublished The was as from a previously in the human EL on the of the EL has been it would likely that these two were evolved to for the of secreted and of EL and to for different of and regulated expression the of Some for this possibility has been by human tissue which have that the two are at different levels in different there is that this in the In addition to the by these of the EL is of to considerable of protein EL have been that are of the lipase the as as of the acid of the roles of these molecules will specific of the expression and of these EL The of EL as a lipase family member was its been by studies of lipid metabolism. of the function of this lipase is thus in to its role the of the lipase Although of EL with the human LPL and acid revealed of the EL has a homology in the (9Jaye M. Lunch K.J. Krawiec J. Marchadier D. Maugeais C. Doan K. South V. Amin D. Perrone M. Rader D.J. A novel endothelial-derived lipase that modulates HDL metabolism.Nat. Genet. 1999; 21: 424-428Google Scholar, 10Hirata K. Dichek H.L. Cioffi J.A. Choi S.Y. Leeper N.J. Quintana L. Kronmal G.S. Cooper A.D. Quertermous T. Cloning of a unique lipase from endothelial cells extends the lipase gene family.J. Biol. Chem. 1999; 274: 14170-14175Google Scholar). The of lipases is to be in substrate Dichek H.L. S. hepatic and lipoprotein lipase: the the site lipase substrate Biol. Chem. Scholar, A. Structure of human pancreatic Scholar, F. C. H. A. C. R. basis for the substrate of pancreatic lipases and related Biophys. Acta. Scholar, M.E. A the site of human pancreatic lipase and lipid Biol. Chem. Scholar, Y. M.E. The pancreatic lipase Lipid Res. 2000; Scholar) as with phospholipase and rat pancreatic lipase-related protein 2 that have a molecular homology but a different substrate from human pancreatic lipase A. F. C. H. F. C. L. A found in pancreatic lipase is in the 1993; Scholar, A. Y. F. R. C. M. Structure and activity of rat pancreatic lipase-related protein Biol. Chem. Scholar). data that the substrate of EL might be different from of LPL and HL. Thus, have to characterize EL as a lipase using cells with the human EL from the LPL or HL, EL in the presence or of (10Hirata K. Dichek H.L. Cioffi J.A. Choi S.Y. Leeper N.J. Quintana L. Kronmal G.S. Cooper A.D. Quertermous T. Cloning of a unique lipase from endothelial cells extends the lipase gene family.J. Biol. Chem. 1999; 274: 14170-14175Google Scholar). activity of EL was also by (9Jaye M. Lunch K.J. Krawiec J. Marchadier D. Maugeais C. Doan K. South V. Amin D. Perrone M. Rader D.J. A novel endothelial-derived lipase that modulates HDL metabolism.Nat. Genet. 1999; 21: 424-428Google Scholar) and more recently by Marchadier D. Maugeais C. Rader D.J. of the activity of endothelial Lipid Res. 2002; Scholar) using from cells with the human EL In to the report by and in which EL has activity (9Jaye M. Lunch K.J. Krawiec J. Marchadier D. Maugeais C. Doan K. South V. Amin D. Perrone M. Rader D.J. A novel endothelial-derived lipase that modulates HDL metabolism.Nat. Genet. 1999; 21: 424-428Google Scholar), Marchadier D. Maugeais C. Rader D.J. of the activity of endothelial Lipid Res. 2002; Scholar) that EL has activity and for activity. Unlike the activity was by the presence of Furthermore, the activity was by the presence of in a Our and that EL has a of phospholipase A1 activity was used as a substrate (9Jaye M. Lunch K.J. Krawiec J. Marchadier D. Maugeais C. Doan K. South V. Amin D. Perrone M. Rader D.J. A novel endothelial-derived lipase that modulates HDL metabolism.Nat. Genet. 1999; 21: 424-428Google Scholar, 10Hirata K. Dichek H.L. Cioffi J.A. Choi S.Y. Leeper N.J. Quintana L. Kronmal G.S. Cooper A.D. Quertermous T. Cloning of a unique lipase from endothelial cells extends the lipase gene family.J. Biol. Chem. 1999; 274: 14170-14175Google Scholar). In the report of Marchadier D. Maugeais C. Rader D.J. of the activity of endothelial Lipid Res. 2002; Scholar), the of to phospholipase activity of EL was with of for and for Thus, EL is primarily a phospholipase with a activity in the presence of data were further by in studies in which EL to have a phospholipase A1 activity in as to or and HDL levels. EL may for most of the phospholipase activity in deficient and unpublished A1 enzymes the fatty acids from Although was used to the phospholipase activity of EL (9Jaye M. Lunch K.J. Krawiec J. Marchadier D. Maugeais C. Doan K. South V. Amin D. Perrone M. Rader D.J. A novel endothelial-derived lipase that modulates HDL metabolism.Nat. Genet. 1999; 21: 424-428Google Scholar, 10Hirata K. Dichek H.L. Cioffi J.A. Choi S.Y. Leeper N.J. Quintana L. Kronmal G.S. Cooper A.D. Quertermous T. Cloning of a unique lipase from endothelial cells extends the lipase gene family.J. Biol. Chem. 1999; 274: 14170-14175Google Scholar), there is a possibility that as phosphatidylserine and will also be It is likely that will be hydrolyzed by this enzyme. It is there are fatty acid for the enzyme. Thus, further studies are to the substrate for this enzyme using different and to the the activity. EL was as a of endothelial cell gene expression and was at a in endothelial cells but its with In the was in a of and (10Hirata K. Dichek H.L. Cioffi J.A. Choi S.Y. Leeper N.J. Quintana L. Kronmal G.S. Cooper A.D. Quertermous T. Cloning of a unique lipase from endothelial cells extends the lipase gene family.J. Biol. Chem. 1999; 274: 14170-14175Google Scholar). were by (9Jaye M. Lunch K.J. Krawiec J. Marchadier D. Maugeais C. Doan K. South V. Amin D. Perrone M. Rader D.J. A novel endothelial-derived lipase that modulates HDL metabolism.Nat. Genet. 1999; 21: 424-428Google Scholar) using The expression of EL in the is different from that of LPL and HL. LPL is in and is synthesized by the and to and endothelial cells or is transported to the endothelial cells in the and of the in the of expression from the vascular to specific the as to its in the is similar to and LPL where it from the cell the endothelial cell to the vascular is the organ in lipoprotein metabolism and EL expression was at a in the by the of EL in of that EL is in the endothelial cells but in the of EL by hepatic endothelial cells was further by in hybridization in and rat Thus, this enzyme is different from LPL or EL functions at the site where it is LPL and are synthesized at site and to site where it The in tissue distribution suggests and functions for and EL their similar and similar molecular The groups that cloned EL that EL is synthesized by the vascular endothelial cells and it can the of Thus, the of EL expression in response to signals as cytokines or cholesterol was is an inflammatory R. inflammatory J. 1999; Scholar) and cytokines are thought to have an role in the expression of a variety of that cell and that are for cytokines that have the most in this are and Thus, the expression of EL by these cytokines in endothelial cells was by Quertermous and (12Hirata K. Ishida T. Matsushita H. Tsao P.S. Quertermous T. Regulated expression of endothelial cell-derived lipase.Biochem. Biophys. Res. Commun. 2000; 272: 90-93Google Scholar). When human endothelial cells as and were with or there was a in EL levels. have been a of studies suggesting that physical in the are to the of atherosclerosis. to the endothelial cells at of induced a in and as by EL levels by data that EL expression in endothelial cells is highly regulated by cytokines and physical to be in the development of atherosclerosis. cholesterol levels are related to the development of of the mechanisms by which cholesterol is with the development of is vascular endothelial have a cholesterol can the expression of EL in EL is synthesized by the vascular endothelial this and animals with a and the presence of EL in the and using specific have levels of cholesterol to the of by the J.A. N. and in 1992; Scholar), and thus have been used as of the of atherosclerosis. that overexpress are to development cholesterol Our data that EL is in the of at a and the of expression is in The of EL expression by cytokines and by cholesterol and the of EL on the of that EL play an role in the development of atherosclerotic lesions. this the physiologic role of EL is and the presence of and however, provide basis for on HDL may a role in lipoprotein metabolism and but it is to The of was in the (10Hirata K. Dichek H.L. Cioffi J.A. Choi S.Y. Leeper N.J. Quintana L. Kronmal G.S. Cooper A.D. Quertermous T. Cloning of a unique lipase from endothelial cells extends the lipase gene family.J. Biol. Chem. 1999; 274: 14170-14175Google Scholar). organ has a and a of blood it is and has to fatty it may the fatty acids of which are in the blood the which has a for fatty and a storage Thus, in the it provide and a of The and Scholar). in the endothelial cells of the raises different this organ can fatty acids from a variety of It is to that it plays a role in the that on the of it was that of this to J.W. of and in the Scholar, T.G. of the of of to the lipoprotein the of in the Scholar) but studies were may the of the to which is most in the by EL may in the of on the with K. A. Hepatic lipase of of Lipid Res. 1993; Scholar) previously that in vitro of with in of to the of on the It is where the of the enzyme is will be to It however, to that a of EL may of the by the of the numerous phospholipase by cytokines and and (12Hirata K. Ishida T. Matsushita H. Tsao P.S. Quertermous T. Regulated expression of endothelial cell-derived lipase.Biochem. Biophys. Res. Commun. 2000; 272: 90-93Google Scholar) may it to fatty acids to of endothelial injury as a of the of lipid levels with has to the of HDL as an of and development of Scholar, T. M.C. as a the J. Scholar, K. primary with in with of in and of J. 1987; Scholar). to of the in HDL cholesterol levels in is but the to this are It is that in levels are by the at which they are but by the of of their are molecules that play a role in levels M. S.Y. R. J.A. J.A. H. their role in vascular Opin. Lipidol. Scholar), D. triglyceride with very lipoprotein triglyceride and Scholar, triglycerides and in Res. Scholar, of lipoprotein lipase and hepatic triglyceride lipase in of with of HDL 1993; Scholar, J. J. A. of hepatic lipase in to a marked of and Natl. Acad. Sci. USA. Scholar), LPL J.R. Jr., T. S. of of very in Natl. Acad. Sci. USA. Scholar, M. R. of lipoprotein lipase in the of lipoprotein metabolism. in and lipoprotein 86: Scholar, in of with very protein and lipoprotein Biophys. Acta. 1992; Scholar, A. G.S. of lipoprotein lipase on of triglycerides and HDL cholesterol from to and of the Scholar, M.C. of lipoprotein lipase, and protein to and HDL in Biol. 2002; Scholar), of human in of human and human on lipoprotein cholesterol D.J. K. N. H. J. M. T. L. S. Jr., of and in and Scholar), cholesterol protein A. J. K. Y. H. lipoprotein levels by a protein gene J. Scholar), and protein S. M. J. C. The of human of lipoprotein for J. Scholar). the has on the HDL in the of cholesterol transport and the of these there to be large in our of HDL metabolism. studies are to HDL may be with to and to affect the atherosclerotic levels are regulated in by of the lipase enzyme family. The lipases have highly and these enzymes function to triglycerides and of this and are in the and metabolism of in lipoprotein genetic and studies that levels are related to of lipoprotein lipase and hepatic triglyceride lipase in of with of HDL 1993; Scholar, J. J. A. of hepatic lipase in to a marked of and Natl. Acad. Sci. USA. Scholar, H. J. of the hepatic lipase gene to the lipoprotein in Lipid Res. 2000; Scholar). When EL was by of human EL there was a in HDL levels (9Jaye M. Lunch K.J. Krawiec J. Marchadier D. Maugeais C. Doan K. South V. Amin D. Perrone M. Rader D.J. A novel endothelial-derived lipase that modulates HDL metabolism.Nat. Genet. 1999; 21: 424-428Google Scholar). our group EL in endothelial cells or EL on the and lipoprotein by protein that overexpress EL showed reduced levels Conversely, that are deficient in EL showed a marked elevation in levels. data that EL may play a physiologic role in HDL metabolism. studies are to the mechanisms by which EL HDL metabolism. LPL on triglyceride on and HDL to their and EL has a role is to It for play a role in of studies will the of that have more levels of and In addition to their it has been that LPL and have that may the and of selective cholesterol transport M. S. Cooper A.D. cells a cell of hepatic of lipoprotein and and selective of Biol. Chem. Scholar, F. W.A. T. S. N. H. Hepatic lipase an in selective of esters by human cells in Scholar, R.D. M. A. Jr., S. Hepatic lipase the selective of esters from in Lipid Res. Scholar, G. J. R.D. Jr., S. Hepatic lipase the selective of esters in Lipid Res. 2000; Scholar). It is to that EL at of these of LPL in was previously in a review by Lipoprotein lipase and roles in metabolism and Lipid Res. Scholar). The is the of its function in lipoprotein The is by the presence of LPL in S. M. D. J. and cells lipoprotein lipase in human and atherosclerotic Natl. Acad. Sci. USA. Scholar, K. D. S. M. A. Lipoprotein lipase is synthesized by cells in human atherosclerotic 1992; Scholar, L. H. M. G. O. of lipoprotein lipase and in from human atherosclerotic 1993; Scholar) and of as in the wall S. T. Lipoprotein lipase the of lipoprotein to on cell and 1992; Scholar, Lipoprotein lipase lipoprotein by cell 1992; Scholar, Lipoprotein lipase (LPL) lipoprotein vascular that LPL in vascular Lipid Res. Scholar). studies suggesting and roles of were previously by S. C. M. The role of hepatic lipase in lipoprotein metabolism and Opin. Lipidol. Scholar). data on and LPL the possibility that EL may also have and roles by lipoprotein metabolism and endothelial EL can the of HDL levels by the its phospholipase activity. Our data in and that EL levels are related to the levels and studies to for in the EL gene that affect HDL levels may be very and to our of the genetic basis of HDL levels. It is also that EL may the metabolism of a as for LPL and HL. The of LPL and on lipoprotein metabolism has been by H.L. J. H. L. of hepatic lipase in and that hepatic lipase as a for lipoprotein Biol. Chem. Scholar, Y. Lipoprotein and of by and 1992; Scholar, in lipoprotein of Biol. Chem. Scholar, S.Y. A.D. Lipoprotein lipase with with Biol. Chem. Scholar, S.Y. Cooper A.D. and hepatic lipase the of Biol. Chem. Scholar, M. Y. H. R. lipoprotein lipase expression in of very lipoprotein direct that lipoprotein lipase in Natl. Acad. Sci. USA. Scholar, H.L. H. Hepatic lipase and levels by a in Lipid Res. Scholar, A. A. In of a role for hepatic lipase in human lipoprotein of its Lipid Res. 2000; Scholar), and this may of the enzyme with cell molecules as and Our data that EL the of as and by cells and unpublished data that this enzyme may play a role in the levels of and thus plays an However, EL in the vascular endothelial cell the of in the wall and thus the to these data EL may also function as a In the discovery of a member of the lipase family that has primarily phospholipase A1 activity and is located on the vascular wall where it can to the physiologic function of and in vascular has a in The is to be endothelial lipase human endothelial cells hepatic lipase human umbilical vein endothelial cells lipoprotein lipase

OBJECTIVE: To examine racial/ethnic differences in the prevalence of diabetic kidney disease (DKD), with and without proteinuria, in an outpatient health care organization. RESEARCH DESIGN AND METHODS: We examined electronic health records for 15,683 persons of non-Hispanic white (NHW), Asian (Asian Indian, Chinese, and Filipino), Hispanic, and non-Hispanic black (NHB) race/ethnicity with type 2 diabetes and no prior history of kidney disease from 2008 to 2010. We directly standardized age- and sex-adjusted prevalence rates of proteinuric DKD (proteinuria with or without low estimated glomerular filtration rate [eGFR]) or nonproteinuric DKD (low eGFR alone). We calculated sex-specific odds ratios of DKD in racial/ethnic minorities (relative to NHWs) after adjustment for traditional DKD risk factors. RESULTS: Racial/ethnic minorities had higher rates of proteinuric DKD than NHWs (24.8-37.9 vs. 24.8%) and lower rates of nonproteinuric DKD (6.3-9.8 vs. 11.7%). On adjusted analyses, Chinese (odds ratio 1.39 for women and 1.56 for men), Filipinos (1.57 for women and 1.85 for men), Hispanics (1.46 for women and 1.34 for men), and NHBs (1.50 for women) exhibited significantly (P < 0.01) higher odds of proteinuric DKD than NHWs. Conversely, Chinese, Hispanic, and NHB women and Hispanic men had significantly lower odds of nonproteinuric DKD than NHWs. CONCLUSIONS: We found novel racial/ethnic differences in DKD among patients with type 2 diabetes. Racial/ethnic minorities were more likely to have proteinuric DKD and less likely to have nonproteinuric DKD. Future research should examine diverse DKD-related outcomes by race/ethnicity to inform targeted prevention and treatment efforts and to explore the etiology of these differences.

BACKGROUND: There is no disease-specific instrument to assess health-related quality of life (HRQL) in patients with idiopathic pulmonary fibrosis (IPF). METHODS: Patients' perspectives were collected to develop domains and items for an IPF-specific HRQL instrument. We used item variance and Rasch analysis to construct the ATAQ-IPF (A Tool to Assess Quality of life in IPF). RESULTS: The ATAQ-IPF version 1 is composed of 74 items comprising 13 domains. All items fit the Rasch model. Domains and the total instrument possess acceptable psychometric characteristics for a multidimensional questionnaire. The pattern of correlations between ATAQ-IPF scores and physiologic variables known to be important in IPF, along with significant differences in ATAQ-IPF scores between subjects using versus those not using supplemental oxygen, support its validity. CONCLUSIONS: Patient-centered and careful statistical methodologies were used to construct the ATAQ-IPF version 1, an IPF-specific HRQL instrument. Simple summation scoring is used to derive individual domain scores as well as a total score. Results support the validity of the ATAQ-IPF, and future studies will build on that validity.

BACKGROUND: The roles of obesity and insulin resistance in asthma and atopy are not well understood. We investigated whether there is an association of obesity and insulin resistance with asthma and atopy prevalence in US adults. METHODS: Data from the 2005-2006 National Health and Nutrition Examination Survey were analyzed by multivariate logistic regression, controlling for sex, age, ethnicity, income, and smoking status. Obesity was measured by body mass index (BMI) and waist circumference, and insulin resistance by the homeostasis model assessment. Asthma was defined by self-report of ever receiving a diagnosis and still having asthma currently, and atopy by any positive specific serum IgE responses to a panel of aeroallergens. RESULTS: Neither obesity measure nor insulin resistance was associated with atopy. Obesity was positively associated with asthma overall (odds ratio [OR] for obese vs normal BMI = 2.28, 95% CI: 1.76, 2.96; OR for obese vs normal waist circumference = 1.75; 95% CI: 1.22, 2.51) but insulin resistance was not (OR = 1.26; 95% CI: 0.80, 1.98). Obesity was also associated with nonatopic asthma (OR for obese vs normal BMI = 2.5; 95% CI: 1.2, 5.2; OR for obese vs normal waist circumference = 2.07, 95% CI: 1.21, 3.54), while obese BMI was also associated with atopic asthma (OR = 2.04, 95% CI: 1.37, 3.03). Obesity remained independently associated with all asthma outcomes after controlling for insulin resistance. CONCLUSION: Obesity was independently associated with asthma, and atopic and nonatopic asthma, after controlling for insulin resistance and socio-demographic factors. There was no evidence that insulin resistance was associated with atopy or asthma.

OBJECTIVE: To educate sports medicine practitioners as to length of time for an athlete to return to activity after sustaining a rupture of the plantar fascia. METHODS: Athletic patients sustaining plantar fascia ruptures and subsequent treatment were reviewed. Diagnosis was based on clinical findings, although radiographic studies were done. Patients were treated for 2 to 3 weeks with a below-knee or high-top boot, nonweightbearing, with an additional 2 to 3 weeks of weightbearing in the boot. Patients used physical therapy. RESULTS: Eighteen athletes, including 6 elite athletes, were evaluated. Mean age was 40.9 +/- 13.2 years. There were 12 males and 6 females. Mean postinjury follow-up was 42 months. Duration of prior plantar fascia symptoms ranged from 0 to 52 weeks. All but 2 ruptures were of the medial portion. Four patients had injections prior to rupture. Five patients wore orthoses preinjury; 14 wore orthoses postinjury. All patients returned to activity after 2 to 26 weeks (mean, 9.1 +/- 6.0 weeks). Running athletes predominantly composed the cohort; others played tennis, volleyball, and basketball. CONCLUSION: Using the treatment protocol, patients sustaining plantar fascia rupture can achieve favorable results with complete return to activity. None of the 18 patients sustained reinjury, had postinjury sequelae, or necessitated surgery, contrary to other studies.