Improving follow-up of abnormal cancer screens using electronic health records: trust but verify test result communication.

BACKGROUND: Early detection of colorectal cancer through timely follow-up of positive Fecal Occult Blood Tests (FOBTs) remains a challenge. In our previous work, we found 40% of positive FOBT results eligible for colonoscopy had no documented response by a treating clinician at two weeks despite procedures for electronic result notification. We determined if technical and/or workflow-related aspects of automated communication in the electronic health record could lead to the lack of response. METHODS: Using both qualitative and quantitative methods, we evaluated positive FOBT communication in the electronic health record of a large, urban facility between May 2008 and March 2009. We identified the source of test result communication breakdown, and developed an intervention to fix the problem. Explicit medical record reviews measured timely follow-up (defined as response within 30 days of positive FOBT) pre- and post-intervention. RESULTS: Data from 11 interviews and tracking information from 490 FOBT alerts revealed that the software intended to alert primary care practitioners (PCPs) of positive FOBT results was not configured correctly and over a third of positive FOBTs were not transmitted to PCPs. Upon correction of the technical problem, lack of timely follow-up decreased immediately from 29.9% to 5.4% (p<0.01) and was sustained at month 4 following the intervention. CONCLUSION: Electronic communication of positive FOBT results should be monitored to avoid limiting colorectal cancer screening benefits. Robust quality assurance and oversight systems are needed to achieve this. Our methods may be useful for others seeking to improve follow-up of FOBTs in their systems.

Timely follow-up of abnormal diagnostic imaging test results in an outpatient setting: are electronic medical records achieving their potential?

BACKGROUND: Given the fragmentation of outpatient care, timely follow-up of abnormal diagnostic imaging results remains a challenge. We hypothesized that an electronic medical record (EMR) that facilitates the transmission and availability of critical imaging results through either automated notification (alerting) or direct access to the primary report would eliminate this problem. METHODS: We studied critical imaging alert notifications in the outpatient setting of a tertiary care Department of Veterans Affairs facility from November 2007 to June 2008. Tracking software determined whether the alert was acknowledged (ie, health care practitioner/provider [HCP] opened the message for viewing) within 2 weeks of transmission; acknowledged alerts were considered read. We reviewed medical records and contacted HCPs to determine timely follow-up actions (eg, ordering a follow-up test or consultation) within 4 weeks of transmission. Multivariable logistic regression models accounting for clustering effect by HCPs analyzed predictors for 2 outcomes: lack of acknowledgment and lack of timely follow-up. RESULTS: Of 123 638 studies (including radiographs, computed tomographic scans, ultrasonograms, magnetic resonance images, and mammograms), 1196 images (0.97%) generated alerts; 217 (18.1%) of these were unacknowledged. Alerts had a higher risk of being unacknowledged when the ordering HCPs were trainees (odds ratio [OR], 5.58; 95% confidence interval [CI], 2.86-10.89) and when dual-alert (>1 HCP alerted) as opposed to single-alert communication was used (OR, 2.02; 95% CI, 1.22-3.36). Timely follow-up was lacking in 92 (7.7% of all alerts) and was similar for acknowledged and unacknowledged alerts (7.3% vs 9.7%; P = .22). Risk for lack of timely follow-up was higher with dual-alert communication (OR, 1.99; 95% CI, 1.06-3.48) but lower when additional verbal communication was used by the radiologist (OR, 0.12; 95% CI, 0.04-0.38). Nearly all abnormal results lacking timely follow-up at 4 weeks were eventually found to have measurable clinical impact in terms of further diagnostic testing or treatment. CONCLUSIONS: Critical imaging results may not receive timely follow-up actions even when HCPs receive and read results in an advanced, integrated electronic medical record system. A multidisciplinary approach is needed to improve patient safety in this area.

Identification of genetic variation influencing apolipoprotein E levels: Follow-up of genome-wide linkage scans in the GENOA study

Apolipoprotein E (ApoE) plays a major role in the metabolism of high density and low density lipoproteins (HDL and LDL). Its common protein isoforms (E2, E3, E4) are risk factors for coronary artery disease (CAD) and explain between 16 to 23% of the inter-individual variation in plasma apoE levels. Linkage analysis has been completed for plasma apoE levels in the GENOA study (Genetic Epidemiology Network of Atherosclerosis). After stratification of the population by lipoprotein levels and body mass index (BMI) to create more homogeneity with regard to biological context for apoE levels, Hispanic families showed significant linkage on chromosome 17q for two strata (LOD=2.93 at 104 cM for a low cholesterol group, LOD=3.04 at 111 cM for a low cholesterol, high HDLC group). Replication of 17q linkage was observed for apoB and apoE levels in the unstratified Hispanic and African-American populations, and for apoE levels in African-American families. Replication of this 17q linkage in different populations and strata provides strong support for the presence of gene(s) in this region with significant roles in the determination of inter-individual variation in plasma apoE levels. Through a positional and functional candidate gene approach, ten genes were identified in the 17q linked region, and 62 polymorphisms in these genes were genotyped in the GENOA families. Association analysis was performed with FBAT, GEE, and variance-component based tests followed by conditional linkage analysis. Association studies with partial coverage of TagSNPs in the gene coding for apolipoprotein H (APOH) were performed, and significant results were found for 2 SNPs (APOH_20951 and APOH_05407) in the Hispanic low cholesterol strata accounting for 3.49% of the inter-individual variation in plasma apoE levels. Among the other candidate genes, we identified a haplotype block in the ACE1 gene that contains two major haplotypes associated with apoE levels as well as total cholesterol, apoB and LDLC levels in the unstratified Hispanic population. Identifying genes responsible for the remaining 60% of inter-individual variation in plasma apoE level, will yield new insights into the understanding of genetic interactions involved in the lipid metabolism, and a more precise understanding of the risk factors leading to CAD. ^

Long Term Follow-up of Morbidity and Quality of Life Associated with Isolated Gastroschisis

Gastroschisis is a birth defect in which an opening in the abdominal wall allows herniation of the viscera. Prenatal counseling regarding gastroschisis typically discusses that, although these infants often endure a difficult neonatal course, they experience few long-term complications. However, information regarding long-term outcomes is based on limited studies that lack specificity. Therefore, we aimed to study the long-term morbidity and quality of life in children born with gastroschisis in a large and diverse population drawn from the Texas Birth Defects Registry (TBDR). Study packets with informed consent, a questionnaire, and the Pediatric Quality of Life Inventory Generic Core Scale 4.0 (PedsQL 4.0) in English and Spanish were mailed to 1,112 parents of children born with isolated gastroschisis in Texas between 1999 and 2008 via the TBDR. Information was abstracted from the TBDR for 58 mothers of children with gastroschisis who returned study materials. Three hundred fifty five packets were returned to sender, giving a response rate of 7.7%. Children born with gastroschisis had quality of life scores that were not significantly different than expected (p = 0.981). However, factors such as having a learning disability (p = 0.001) and missing school due to gastrointestinal issues (p = 0.020) were found to significantly decrease quality of life. Overall, children with gastroschisis had a significantly increased risk for learning disabilities regardless of whether they were preterm (p = 0.021) or full term (p = 0.021). Additionally, there appeared to be an increased risk for auditory impairment in Caucasian children (p < 0.0005). Therefore, while overall long-term quality of life is not significantly altered for children born with gastroschisis, the previously unreported increased risk for learning disabilities and possible association with hearing impairment are important findings that should be conveyed to prospective parents.

Federally regulated institutional review boards: The aspects of a "model" IRB---Is the current system in need of a tune up or complete overhaul?

Institutional Review Boards (IRBs) are the primary gatekeepers for the protection of ethical standards of federally regulated research on human subjects in this country. This paper focuses on what general, broad measures that may be instituted or enhanced to exemplify a "model IRB". This is done by examining the current regulatory standards of federally regulated IRBs, not private or commercial boards, and how many of those standards have been found either inadequate or not generally understood or followed. The analysis includes suggestions on how to bring about changes in order to make the IRB process more efficient, less subject to litigation, and create standardized educational protocols for members. The paper also considers how to include better oversight for multi-center research, increased centralization of IRBs, utilization of Data Safety Monitoring Boards when necessary, payment for research protocol review, voluntary accreditation, and the institution of evaluation/quality assurance programs. ^ This is a policy study utilizing secondary analysis of publicly available data. Therefore, the research for this paper focuses on scholarly medical/legal journals, web information from the Department of Health and Human Services, Federal Drug Administration, and the Office of the Inspector General, Accreditation Programs, law review articles, and current regulations applicable to the relevant portions of the paper. ^ Two issues are found to be consistently cited by the literature as major concerns. One is a need for basic, standardized educational requirements across all IRBs and its members, and secondly, much stricter and more informed management of continuing research. There is no federally regulated formal education system currently in place for IRB members, except for certain NIH-based trials. Also, IRBs are not keeping up with research once a study has begun, and although regulated to do so, it does not appear to be a great priority. This is the area most in danger of increased litigation. Other issues such as voluntary accreditation and outcomes evaluation are slowing gaining steam as the processes are becoming more available and more sought after, such as JCAHO accrediting of hospitals. ^ Adopting the principles discussed in this paper should promote better use of a local IRBs time, money, and expertise for protecting the vulnerable population in their care. Without further improvements to the system, there is concern that private and commercial IRBs will attempt to create a monopoly on much of the clinical research in the future as they are not as heavily regulated and can therefore offer companies quicker and more convenient reviews. IRBs need to consider the advantages of charging for their unique and important services as a cost of doing business. More importantly, there must be a minimum standard of education for all IRB members in the area of the ethical standards of human research and a greater emphasis placed on the follow-up of ongoing research as this is the most critical time for study participants and may soon lead to the largest area for litigation. Additionally, there should be a centralized IRB for multi-site trials or a study website with important information affecting the trial in real time. There needs to be development of standards and metrics to assess the performance of the IRBs for quality assurance and outcome evaluations. The boards should not be content to run the business of human subjects' research without determining how well that function is actually being carried out. It is important that federally regulated IRBs provide excellence in human research and promote those values most important to the public at large.^

Metabolic syndrome and cardiovascular mortality among participants of the hypertension detection and follow-up program

Metabolic Syndrome (MetS) is a clustering of cardiovascular (CV) risk factors that includes obesity, dyslipidemia, hyperglycemia, and elevated blood pressure. Applying the criteria for MetS can serve as a clinically feasible tool for identifying patients at high risk for CV morbidity and mortality, particularly those who do not fall into traditional risk categories. The objective of this study was to examine the association between MetS and CV mortality among 10,940 American hypertensive adults, ages 30-69 years, participating in a large randomized controlled trial of hypertension treatment (HDFP 1973-1983). MetS was defined as the presence of hypertension and at least two of the following risk factors: obesity, dyslipidemia, or hyperglycemia. Of the 10,763 individuals with sufficient data available for analysis, 33.2% met criteria for MetS at baseline. The baseline prevalence of MetS was significantly higher among women (46%) than men (22%) and among non-blacks (37%) versus blacks (30%). All-cause and CV mortality was assessed for 10,763 individuals. Over a median follow-up of 7.8 years, 1,425 deaths were observed. Approximately 53% of these deaths were attributed to CV causes. Compared to individuals without MetS at baseline, those with MetS had higher rates of all-cause mortality (14.5% v. 12.6%) and CV mortality (8.2% versus 6.4%). The unadjusted risk of CV mortality among those with MetS was 1.31 (95% confidence interval [CI], 1.12-1.52) times that for those without MetS at baseline. After multiple adjustment for traditional risk factors of age, race, gender, history of cardiovascular disease (CVD), and smoking status, individuals with MetS, compared to those without MetS, were 1.42 (95% CI, 1.20-1.67) times more likely to die of CV causes. Of the individual components of MetS, hyperglycemia/diabetes conferred the strongest risk of CV mortality (OR 1.73; 95% CI, 1.39-2.15). Results of the present study suggest MetS defined as the presence of hypertension and 2 additional cardiometabolic risk factors (obesity, dyslipidemia, or hyperglycemia/diabetes) can be used with some success to predict CV mortality in middle-aged hypertensive adults. Ongoing and future prospective studies are vital to examine the association between MetS and cardiovascular morbidity and mortality in select high-risk subpopulations, and to continue evaluating the public health impact of aggressive, targeted screening, prevention, and treatment efforts to prevent future cardiovascular disability and death.^