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Closing the Feedback Loop: An Interactive Voice Response System to Provide Follow-up and Feedback in Primary Care Settings

Fri, 04/25/2014 - 4:12pm

In primary care settings, follow-up regarding the outcome of acute outpatient visits is largely absent. We sought to develop an automated interactive voice response system (IVRS) for patient follow-up with feedback to providers capable of interfacing with multiple pre-existing electronic medical records (EMRs). A system was designed to extract data from EMRs, integrate with the IVRS, call patients for follow-up, and provide a feedback report to providers. Challenges during the development process were analyzed and summarized. The components of the technological solution and details of its implementation are reported. Lessons learned include: (1) Modular utilization of system components is often needed to adapt to specific clinic workflow and patient population needs (2) Understanding the local telephony environment greatly impacts development and is critical to success, and (3) Ample time for development of the IVRS questionnaire (mapping all branching paths) and speech recognition tuning (sensitivity, use of barge-in tuning, use of "known voice") is needed. With proper attention to design and development, modular follow-up and feedback systems can be integrated into existing EMR systems providing the benefits of IVRS follow-up to patients and providers across diverse practice settings.

Mediation of smoking-associated postoperative mortality by perioperative complications in veterans undergoing elective surgery: data from Veterans Affairs Surgical Quality Improvement Program (VASQIP)--a cohort study

Fri, 04/25/2014 - 4:12pm

OBJECTIVE: To assess the mediation of smoking-associated postoperative mortality by postoperative complications.

DESIGN: Observational cohort study.

SETTING: Using data from the Veterans Affairs (VA) Surgical Quality Improvement Programme, a quality assurance programme for major surgical procedures in the VA healthcare system, we assessed the association of current smoking at the time of the surgery with 6-month and 1-year mortality.

PRIMARY AND SECONDARY OUTCOME MEASURES: Using mediation analyses, we calculated the relative contribution of each smoking-associated complication to smoking-associated postoperative mortality, both unadjusted and adjusted for age, race/ethnicity, work relative value unit of the operation, surgeon specialty, American Society of Anesthesiologists class and year of surgery. Smoking-associated complications included surgical site infection (SSI), cardiovascular complications (myocardial infarction, cardiac arrest and/or stroke) and pulmonary complications (pneumonia, failure to wean and/or reintubation).

RESULTS: There were 186 632 never smokers and 135 741 current smokers. The association of smoking and mortality was mediated by smoking-related complications with varying effects. In unadjusted analyses, the proportions of mediation of smoking to 6-month mortality explained by the complications were as follows: SSIs 22%, cardiovascular complications 12% and pulmonary complications 89%. In adjusted analyses, the per cents mediated by each complication were as follows: SSIs 2%, cardiovascular complications 4% and pulmonary complications 22%. In adjusted analyses for 1-year mortality, respective per cents mediated were 2%, 3% and 16%.

CONCLUSIONS: Pulmonary complications, followed by cardiovascular complications and SSIs were mediators of smoking-associated 6-month and 1-year mortality. Interventions targeting smoking cessation and prevention and early treatment of pulmonary complications has the likelihood of reducing postoperative mortality after elective surgery.

Implementing point of care "e-referrals" in 137 clinics to increase access to a quit smoking internet system: the Quit-Primo and National Dental PBRN HI-QUIT Studies

Fri, 04/25/2014 - 4:12pm

Integrating electronic referral systems into clinical practices may increase use of web-accessible tobacco interventions. We report on our feasibility evaluation of using theory-driven implementation science techniques to translate an e-referral system (ReferASmoker.org) into the workflow of 137 community-based medical and dental practices, including system use, patient registration, implementation costs, and lessons learned. After 6 months, 2,376 smokers were e-referred (medical, 1,625; dental, 751). Eighty-six percent of the medical practices [75/87, mean referral = 18.7 (SD = 17.9), range 0-105] and dental practices [43/50, mean referral = 15.0 (SD = 10.5), range 0-38] had e-referred. Of those smokers e-referred, 25.3 registered [mean smoker registration rate-medical 4.9 (SD = 7.6, range 0-59), dental 3.6 (SD = 3.0, range 0-10)]. Estimated mean implementation costs are medical practices, US$429.00 (SD = 85.3); and dental practices, US$238.75 (SD = 13.6). High performing practices reported specific strategies to integrate ReferASmoker.org; low performers reported lack of smokers and patient disinterest in the study. Thus, a majority of practices e-referred and 25.3 % of referred smokers registered demonstrating e-referral feasibility. However, further examination of the identified implementation barriers is important as of the estimated 90,000 to 140,000 smokers seen in the 87 medical practices in 6 months, only 1,625 were e-referred.

Variations in tobacco control in National Dental PBRN practices: the role of patient and practice factors

Fri, 04/25/2014 - 4:12pm

We engaged dental practices enrolled in The National Dental Practice-Based Research Network to quantify tobacco screening (ASK) and advising (ADVISE); and to identify patient and practice -characteristics associated with tobacco control. Dental practices (N = 190) distributed patient surveys that measured ASK and ADVISE. Twenty-nine percent of patients were ASKED about tobacco use during visit, 20% were identified as tobacco users, and 41% reported being ADVISED. Accounting for clustering of patients within practices, younger age and male gender were positively associated with ASK and ADVISE. Adjusting for patient age and gender, a higher proportion of non-whites in the practice, preventive services and proportion on public assistance were positively associated with ASK. Proportion of tobacco users in the practice and offering other preventive services were more strongly associated with ASK and ADVISE than other practice characteristics. Understanding variations in performance is an important step toward designing strategies for improving tobacco control in dentistry.

Genome-wide assessment of post-transcriptional control in the fly brain

Fri, 04/25/2014 - 4:12pm

Post-transcriptional control of gene expression has central importance during development and adulthood and in physiology in general. However, little is known about the extent of post-transcriptional control of gene expression in the brain. Most post-transcriptional regulatory effectors (e.g., miRNAs) destabilize target mRNAs by shortening their polyA tails. Hence, the fraction of a given mRNA that it is fully polyadenylated should correlate with its stability and serves as a good measure of post-transcriptional control. Here, we compared RNA-seq datasets from fly brains that were generated either from total (rRNA-depleted) or polyA-selected RNA. By doing this comparison we were able to compute a coefficient that measures the extent of post-transcriptional control for each brain-expressed mRNA. In agreement with current knowledge, we found that mRNAs encoding ribosomal proteins, metabolic enzymes, and housekeeping genes are among the transcripts with least post-transcriptional control, whereas mRNAs that are known to be highly unstable, like circadian mRNAs and mRNAs expressing synaptic proteins and proteins with neuronal functions, are under strong post-transcriptional control. Surprisingly, the latter group included many specific groups of genes relevant to brain function and behavior. In order to determine the importance of miRNAs in this regulation, we profiled miRNAs from fly brains using oligonucleotide microarrays. Surprisingly, we did not find a strong correlation between the expression levels of miRNAs in the brain and the stability of their target mRNAs; however, genes identified as highly regulated post-transcriptionally were strongly enriched for miRNA targets. This demonstrates a central role of miRNAs for modulating the levels and turnover of brain-specific mRNAs in the fly.

Assessing patient-centered communication in cancer care: stakeholder perspectives

Fri, 04/25/2014 - 4:12pm

PURPOSE: Patient-centered communication is critical to quality cancer care. Effective communication can help patients and family members cope with cancer, make informed decisions, and effectively manage their care; suboptimal communication can contribute to care breakdowns and undermine clinician-patient relationships. The study purpose was to explore stakeholders' views on the feasibility and acceptability of collecting self-reported patient and family perceptions of communication experiences while receiving cancer care. The results were intended to inform the design, development, and implementation of a structured and generalizable patient-level reporting system.

METHODS: This was a formative, qualitative study that used semistructured interviews with cancer patients, family members, clinicians, and leaders of health care organizations. The constant comparative method was used to identify major themes in the interview transcripts.

RESULTS: A total of 106 stakeholders were interviewed. Thematic saturation was achieved. All stakeholders recognized the importance of communication and endorsed efforts to improve communication during cancer care. Patients, clinicians, and leaders expressed concerns about the potential consequences of reports of suboptimal communication experiences, such as damage to the clinician-patient relationship, and the need for effective improvement strategies. Patients and family members would report good communication experiences in order to encourage such practices. Practical and logistic issues were identified.

CONCLUSION: Patient reports of their communication experiences during cancer care could increase understanding of the communication process, stimulate improvements, inform interventions, and provide a basis for evaluating changes in communication practices. This qualitative study provides a foundation for the design and pilot testing of such a patient reporting system.

A single intravenous rAAV injection as late as P20 achieves efficacious and sustained CNS Gene therapy in canavan mice

Fri, 04/25/2014 - 4:12pm

Canavan's disease (CD) is a fatal pediatric leukodystrophy caused by mutations in aspartoacylase (AspA) gene. Currently, there is no effective treatment for CD; however, gene therapy is an attractive approach to ameliorate the disease. Here, we studied progressive neuropathology and gene therapy in short-lived (≤ 1 month) AspA(-/-) mice, a bona-fide animal model for the severest form of CD. Single intravenous (IV) injections of several primate-derived recombinant adeno-associated viruses (rAAVs) as late as postnatal day 20 (P20) completely rescued their early lethality and alleviated the major disease symptoms, extending survival in P0-injected rAAV9 and rAAVrh8 groups to as long as 2 years thus far. We successfully used microRNA (miRNA)-mediated post-transcriptional detargeting for the first time to restrict therapeutic rAAV expression in the central nervous system (CNS) and minimize potentially deleterious effects of transgene overexpression in peripheral tissues. rAAV treatment globally improved CNS myelination, although some abnormalities persisted in the content and distribution of myelin-specific and -enriched lipids. We demonstrate that systemically delivered and CNS-restricted rAAVs can serve as efficacious and sustained gene therapeutics in a model of a severe neurodegenerative disorder even when administered as late as P20.

Adult Willingness to Use Email and Social Media for Peer-to-Peer Cancer Screening Communication: Quantitative Interview Study

Fri, 04/25/2014 - 4:12pm

BACKGROUND: Adults over age 40 are increasing their use of email and social media, raising interest in use of peer-to-peer Internet-based messaging to promote cancer screening.

OBJECTIVE: The objective of our study was to assess current practices and attitudes toward use of email and other e-communication for peer-to-peer dialogues on cancer screening.

METHODS: We conducted in-person interviews with 438 insured adults ages 42-73 in Georgia, Hawaii, and Massachusetts. Participants reported on use of email and other e-communication including social media to discuss with peers routine health topics including breast and colorectal cancer (CRC). We ascertained willingness to share personal CRC screening experiences via conversation, postcard, email, or other e-communication. Health literacy scores were measured.

RESULTS: Email had been used by one-third (33.8%, 148/438) to discuss routine health topics, by 14.6% (64/438) to discuss breast cancer screening, and by 12.6% (55/438) to discuss CRC screening. Other e-communication was used to discuss routine health topics (11.6%, 51/438), screening for breast cancer (3.9%, 17/438), and CRC (2.3%, 10/438). In the preceding week, 84.5% (370/438) of participants had used email, 55.9% (245/438) had used e-communication of some type; 44.3% (194/438) text, 32.9% (144/438) Facebook, 12.3% (54/438) instant message, 7.1% (31/438) video chat, and 4.8% (21/438) Twitter. Many participants were willing to share their CRC screening experiences via email (32.4%, 142/438 might be willing; 36.3%, 159/438 very willing) and via other e-communication (15.8%, 69/438 might be willing; 14.4%, 63/438 very willing). Individuals willing to send CRC screening emails scored significantly higher on tests of health literacy compared to those willing to send only postcards (P<.001).

CONCLUSIONS: Many adults are willing to use email and e-communication to promote cancer screening to peers. Optimal approaches for encouraging peer-to-peer transmission of accurate and appropriate cancer screening messages must be studied.

The association between health literacy and cancer-related attitudes, behaviors, and knowledge

Fri, 04/25/2014 - 4:12pm

Using a multidimensional assessment of health literacy (the Cancer Message Literacy Test-Listening, the Cancer Message Literacy Test-Reading, and the Lipkus Numeracy Scale), the authors assessed a stratified random sample of 1013 insured adults (40-70 years of age). The authors explored whether low health literacy across all 3 domains (n =111) was associated with sets of variables likely to affect engagement in cancer prevention and screening activities: (a) attitudes and behaviors relating to health care encounters and providers, (b) attitudes toward cancer and health, (c) knowledge of cancer screening tests, and (d) attitudes toward health related media and actual media use. Adults with low health literacy were more likely to report avoiding doctor's visits, to have more fatalistic attitudes toward cancer, to be less accurate in identifying the purpose of cancer screening tests, and more likely to avoid information about diseases they did not have. Compared with other participants, those with lower health literacy were more likely to say that they would seek information about cancer prevention or screening from a health care professional and less likely to turn to the Internet first for such information. Those with lower health literacy reported reading on fewer days and using the computer on fewer days than did other participants. The authors assessed the association of low health literacy with colorectal cancer screening in an age-appropriate subgroup for which colorectal cancer screening is recommended. In these insured subjects receiving care in integrated health care delivery systems, those with low health literacy were less likely to be up to date on screening for colorectal cancer, but the difference was not statistically significant.

Commonly used data-collection approaches in clinical research

Fri, 04/25/2014 - 4:12pm

We provide an overview of the different data-collection approaches that are commonly used in carrying out clinical, public health, and translational research. We discuss several of the factors that researchers need to consider in using data collected in questionnaire surveys, from proxy informants, through the review of medical records, and in the collection of biologic samples. We hope that the points raised in this overview will lead to the collection of rich and high-quality data in observational studies and randomized controlled trials.

The impact of cardiac and noncardiac comorbidities on the short-term outcomes of patients hospitalized with acute myocardial infarction: a population-based perspective

Fri, 04/25/2014 - 4:12pm

OBJECTIVES: The objectives of our large observational study were to describe the prevalence of cardiac and noncardiac comorbidities in a community-based population of patients hospitalized with acute myocardial infarction (AMI) at all medical centers in central Massachusetts, and to examine whether multiple comorbidities were associated with in-hospital death rates and hospital length of stay.

METHODS: The study sample consisted of 2,972 patients hospitalized with AMI at all eleven greater Worcester medical centers in central Massachusetts during the three study years of 2003, 2005, and 2007.

RESULTS: The average age of this hospitalized population was 71 years, 55% were men, 93% were Caucasian, and approximately one third had developed an ST segment elevation AMI during the years under study. Hypertension (75%) was the most common cardiac condition identified in patients hospitalized with AMI whereas renal disease (22%) was the most common noncardiac comorbidity diagnosed in this study population. Approximately one in every four hospitalized patients had any four or more of the seven cardiac conditions examined, while one in 13 had any three or more of the five noncardiac conditions studied. Patients with four or more cardiac comorbidities were more than twice as likely to have died during hospitalization and have a prolonged hospital length of stay, compared to those without any cardiac comorbidities. Patients with three or more noncardiac comorbidities had markedly increased odds of dying during hospitalization and having a prolonged hospital stay compared to those with no noncardiac comorbidities previously diagnosed.

CONCLUSION: Our findings highlight the need for additional contemporary data to improve the short-term outcomes of patients hospitalized with AMI and multiple concurrent medical illnesses.

Widespread spinal cord transduction by intrathecal injection of rAAV delivers efficacious RNAi therapy for amyotrophic lateral sclerosis

Fri, 04/25/2014 - 4:12pm

Amyotrophic lateral sclerosis (ALS) causes motor neuron degeneration and paralysis. No treatment can significantly slow or arrest the disease progression. Mutations in the SOD1 gene cause a subset of familial ALS by a gain of toxicity. In principle, these cases could be treated with RNAi that destroys the mutant mRNA, thereby abolishing the toxic protein. However, no system is available to efficiently deliver the RNAi therapy. Recombinant adenoassociated virus (rAAV) is a promising vehicle due to its long-lasting gene expression and low toxicity. However, ALS afflicts broad areas of the central nervous system (CNS). A lack of practical means to spread rAAV broadly has hindered its application in treatment of ALS. To overcome this barrier, we injected several rAAV serotypes into the cerebrospinal fluid. We found that some rAAV serotypes such as rAAVrh10 and rAAV9 transduced cells throughout the length of the spinal cord following a single intrathecal injection and in the broad forebrain following a single injection into the third ventricle. Furthermore, a single intrathecal injection of rAAVrh10 robustly transduced motor neurons throughout the spinal cord in a non-human primate. These results suggested a therapeutic potential of this vector for ALS. To test this, we injected a rAAVrh10 vector that expressed an artificial miRNA targeting SOD1 into the SOD1G93A mice. This treatment knocked down the mutant SOD1 expression and slowed the disease progression. Our results demonstrate the potential of rAAVs for delivering gene therapy to treat ALS and other diseases that afflict broad areas of the CNS.

Utilization of epidermal growth factor receptor (EGFR) testing in the United States: a case study of T3 translational research

Fri, 04/25/2014 - 4:12pm

PURPOSE: We examined hospital use of the epidermal growth factor receptor assay in patients with lung cancer in the United States. Our goal was to inform the development of a model to predict phase 3 translation of guideline-directed molecular diagnostic tests.

METHODS: This was a retrospective observational study. Using logistic regression, we analyzed the association between hospitals' institutional and regional characteristics and the likelihood that an epidermal growth factor receptor assay would be ordered.

RESULTS: Significant institutional predictors included affiliation with an academic medical center (odds ratio, 1.48; 95% confidence interval, 1.20-1.83), participation in a National Cancer Institute clinical research cooperative group (odds ratio, 2.06, 1.66-2.55), and -availability of positron emission tomography scan (odds ratio, 1.44, 1.07-1.94) and cardiothoracic surgery (odds ratio, 1.90, 1.52-2.37) services. Significant regional predictors included metropolitan county (odds ratio, 2.08, 1.48-2.91), population with above-average education (odds ratio, 1.46, 1.09-1.96), and population with above-average income (odds ratio, 1.46, 1.04-2.05). Distance from a National Cancer Institute cancer center was a negative predictor (odds ratio, 0.996, 0.995-0.998), with a 34% decrease in likelihood for every 100 miles.

CONCLUSION: In 2010, only 12% of US acute-care hospitals ordered the epidermal growth factor receptor assay, suggesting that most patients with lung cancer did not have access to this test. This case study illustrated the need for: (i) increased dissemination and implementation research, and (ii) interventions to improve adoption of guideline-directed molecular diagnostic tests by community hospitals.

Share2Quit: Web-Based Peer-Driven Referrals for Smoking Cessation

Fri, 04/25/2014 - 4:12pm

BACKGROUND: Smoking is the number one preventable cause of death in the United States. Effective Web-assisted tobacco interventions are often underutilized and require new and innovative engagement approaches. Web-based peer-driven chain referrals successfully used outside health care have the potential for increasing the reach of Internet interventions.

OBJECTIVE: The objective of our study was to describe the protocol for the development and testing of proactive Web-based chain-referral tools for increasing the access to Decide2Quit.org, a Web-assisted tobacco intervention system.

METHODS: We will build and refine proactive chain-referral tools, including email and Facebook referrals. In addition, we will implement respondent-driven sampling (RDS), a controlled chain-referral sampling technique designed to remove inherent biases in chain referrals and obtain a representative sample. We will begin our chain referrals with an initial recruitment of former and current smokers as seeds (initial participants) who will be trained to refer current smokers from their social network using the developed tools. In turn, these newly referred smokers will also be provided the tools to refer other smokers from their social networks. We will model predictors of referral success using sample weights from the RDS to estimate the success of the system in the targeted population.

RESULTS: This protocol describes the evaluation of proactive Web-based chain-referral tools, which can be used in tobacco interventions to increase the access to hard-to-reach populations, for promoting smoking cessation.

CONCLUSIONS: Share2Quit represents an innovative advancement by capitalizing on naturally occurring technology trends to recruit smokers to Web-assisted tobacco interventions.

Comparison between two labeled agents in mice using a coinjection-ratio approach in contrast to a conventional group approach

Fri, 04/25/2014 - 4:12pm

INTRODUCTION: The differences between two agents often need to be accurately defined in vivo. Usually they are injected respectively into two groups of subjects. However, if the two agents do not interact with each other in vivo, a coinjection would serve the same purpose. We believe some individual differences in biodistribution may be circumvented through this approach by calculating organ level ratios.

METHODS: A model system of MORF/cMORF pretargeting (MORF/cMORF is a complementary pair of DNA analogues) was employed in connection with an on-going tumor therapeutic project. Human LS174T cells were implanted into the flank of severely immuno-compromised NOD-scid IL2rg(null) mice. The tumor was confirmed to express TAG-72 antigens. At 16 days post tumor inoculation, mice received IV 60 mug of MORF-conjugated CC49 (an antiTAG-72 antibody), followed 2 days later by a low-mass-dose IV coinjection containing 2.5 mug of (90)Y-cMORF and 2.5 mug of (99m)Tc-cMORF. At 3 h post radioactivity injection, the distribution of (99m)Tc was imaged on a SPECT/CT camera and then organs were excised and counted for (90)Y and (99m)Tc. Because the two labeled cMORFs do not react or interact with each other in vivo, the two groups of (90)Y and (99m)Tc data enabled a conventional group comparison. In a new effort, (90)Y/(99m)Tc ratios were calculated. Student's t-test and retrospective power analysis were performed for both approaches. In the new approach, the ratios were set at 1 as the null hypothesis.

RESULTS: The Student's t-test in the conventional group approach indicated that the two labeled cMORFs distributed similarly, but significant differences were observed in salivary gland and large intestines. The coinjection-ratio approach certainly did not subvert the results of the conventional approach but revealed subtler differences. The P values were reduced, the powers were increased in most organs, and more significant differences were observed. The increased sensitivity was due to the reduced CV%s (SD/average*100%) of the (90)Y/(99m)Tc ratios. Therefore, some individual differences were circumvented and notably the ratio approach differentiated individual differences into ratio-correctable and ratio-uncorrectable.

CONCLUSIONS: Although the conventional approach is reliable, the coinjection-ratio approach using organ level ratios is more sensitive and therefore is recommended whenever possible. In addition, it differentiates individual differences into "coinjection correctable" and "coinjection uncorrectable".

Health-care access and weight change among young adults: the Coronary Artery Risk Development in Young Adults (CARDIA) Study

Fri, 04/25/2014 - 4:12pm

OBJECTIVE: Health-care access is associated with improved control of multiple chronic diseases, but the association between health-care access and weight change is unclear. The present study aims to test the association between health-care access and weight change.

DESIGN: The Coronary Artery Risk Development in Young Adults (CARDIA) Study is a multicentre population-based prospective study. Weight change was calculated at 3 and 13 years after CARDIA year 7 (1992-1993). Health-care access was defined as no barriers or one or more barriers to access (health insurance gap, no usual source of care, not seeking care due to expense). Intermediary variables evaluated included history of dieting and use of diet pills, meal replacements or weight-control programmes.

SETTING: Four cities in the USA.

SUBJECTS: Participants were aged 18-30 years at baseline (1985-1986). Analyses include 3922 black and white men and women with relevant data from CARDIA years 7, 10 and 20 (1992-1993, 1995-1996 and 2005-2006, respectively).

RESULTS: Mean weight change was +2.22 kg (+4.9 lb) by 3 years and +8.48 kg (+18.7 lb) by 13 years, with no differences by health-care access. Being on a weight-reducing diet was not consistently associated with health-care access across examinations. Use of diet pills, meal replacements or organized weight-control programmes was low, and did not vary by health-care access.

CONCLUSIONS: Weight gain was high irrespective of health-care access. Public health and clinical approaches are needed to address weight gain.

Smoking Topography in Korean American and White Men: Preliminary Findings

Fri, 04/25/2014 - 4:12pm

This is the first study of Korean Americans' smoking behavior using a topography device. Korean American men smoke at higher rates than the general U.S. population. Korean American and White men were compared based on standard tobacco assessment and smoking topography measures. They smoked their preferred brand of cigarettes ad libitum with a portable smoking topography device for 24 h. Compared to White men (N = 26), Korean American men (N = 27) were more likely to smoke low nicotine-yield cigarettes (p < 0.001) and have lower Fagerstrom nicotine dependence scores (p = 0.04). Koreans smoked fewer cigarettes with the device (p = 0.01) than Whites. Controlling for the number of cigarettes smoked, Koreans smoked with higher average puff flows (p = 0.05), greater peak puff flows (p = 0.02), and shorter interpuff intervals (p < 0.001) than Whites. Puff counts, puff volumes, and puff durations did not differ between the two groups. This study offers preliminary insight into unique smoking patterns among Korean American men who are likely to smoke low nicotine-yield cigarettes. We found that Korean American men compensated their lower number and low nicotine-yield cigarettes by smoking with greater puff flows and shorter interpuff intervals than White men, which may suggest exposures to similar amounts of nicotine and harmful tobacco toxins by both groups. Clinicians will need to consider in identifying and treating smokers in a mutually aggressive manner, irrespective of cigarette type and number of cigarette smoked per day.

Validation of anaphylaxis in the Food and Drug Administration's Mini-Sentinel

Fri, 04/25/2014 - 4:12pm

PURPOSE: We aim to develop and validate the positive predictive value (PPV) of an algorithm to identify anaphylaxis using health plan administrative and claims data. Previously published PPVs for anaphylaxis using International Classification of Diseases, ninth revision, Clinical Modification (ICD-9-CM) codes range from 52% to 57%.

METHODS: We conducted a retrospective study using administrative and claims data from eight health plans. Using diagnosis and procedure codes, we developed an algorithm to identify potential cases of anaphylaxis from the Mini-Sentinel Distributed Database between January 2009 and December 2010. A random sample of medical charts (n = 150) was identified for chart abstraction. Two physician adjudicators reviewed each potential case. Using physician adjudicator judgments on whether the case met diagnostic criteria for anaphylaxis, we calculated a PPV for the algorithm.

RESULTS: Of the 122 patients for whom complete charts were received, 77 were judged by physician adjudicators to have anaphylaxis. The PPV for the algorithm was 63.1% (95%CI: 53.9-71.7%), using the clinical criteria by Sampson as the gold standard. The PPV was highest for inpatient encounters with ICD-9-CM codes of 995.0 or 999.4. By combining only the top performing ICD-9-CM codes, we identified an algorithm with a PPV of 75.0%, but only 66% of cases of anaphylaxis were identified using this modified algorithm.

CONCLUSIONS: The PPV for the ICD-9-CM-based algorithm for anaphylaxis was slightly higher than PPV estimates reported in prior studies, but remained low. We were able to identify an algorithm that optimized the PPV but demonstrated lower sensitivity for anaphylactic events.

Gene expression and genetic variation in human atria

Fri, 04/25/2014 - 4:12pm

BACKGROUND: The human left and right atria have different susceptibilities to develop atrial fibrillation (AF). However, the molecular events related to structural and functional changes that enhance AF susceptibility are still poorly understood.

OBJECTIVE: The purpose of this study was to characterize gene expression and genetic variation in human atria.

METHODS: We studied the gene expression profiles and genetic variations in 53 left atrial and 52 right atrial tissue samples collected from the Myocardial Applied Genomics Network (MAGNet) repository. The tissues were collected from heart failure patients undergoing transplantation and from unused organ donor hearts with normal ventricular function. Gene expression was profiled using the Affymetrix GeneChip Human Genome U133A Array. Genetic variation was profiled using the Affymetrix Genome-Wide Human SNP Array 6.0.

RESULTS: We found that 109 genes were differentially expressed between left and right atrial tissues. A total of 187 and 259 significant cis-associations between transcript levels and genetic variants were identified in left and right atrial tissues, respectively. We also found that a single nucleotide polymorphism at a known AF locus, rs3740293, was associated with the expression of MYOZ1 in both left and right atrial tissues.

CONCLUSION: We found a distinct transcriptional profile between the right and left atrium and extensive cis-associations between atrial transcripts and common genetic variants. Our results implicate MYOZ1 as the causative gene at the chromosome 10q22 locus for AF.