Myrna M. Khan

Effect of brain edema on infarct volume in a focal cerebral ischemia model in rats.

Background and Purpose Infarct volume is one of the common indexes for assessing the extent of ischemic brain injury following focal cerebral ischemia. Accuracy in the measurement of infarct volume is compounded by postischemic brain edema that may increase brain volume in the infarcted region. We evaluated the effect of brain edema on infarct volume determined by triphenyltetrazolium chloride and hematoxylin and eosin stains in a focal cerebral ischemia model in rats. Methods In a middle cerebral artery occlusion model in rats, infarction is confined to the cerebral cortex. The infarct was delineated by triphenyltetrazolium chloride stain and, in selected samples, by hematoxylin and eosin stain. We determined infarct size at different times after the ischemic insult (6 hours to 7 days) in relation to the evolution of brain edema by the direct measurement of infarct volume. Indirect measurement to reduce the effect of edema on infarct volume was also conducted in the same brain samples. Results Direct measurement showed that infarct volume fluctuated with the evolution of brain edema (one-way analysis of variance, p< 0.0001). Infarct volume determined by indirect measurement was independent of the extent of brain edema and remained stable from 6 hours to 3 days after ischemia. There was a good correlation between triphenyltetrazolium chloride and hematoxylin and eosin stains in delineating infarct volume with both direct and indirect measurement. Conclusion Traditional direct measurement of infarct volume is associated with an overestimation of infarct volume during the development of brain edema in the first 3 days after ischemia. This artifact can be reduced with indirect measurement, which is based on noninfarcted cortex volume.

A retrospective cohort study: 10-year trend of disease-modifying antirheumatic drugs and biological agents use in patients with rheumatoid arthritis at Veteran Affairs Medical Centers

Objectives To evaluate the trends in patterns of disease-modifying antirheumatic drugs (DMARDs) and biological agents use from 1999 to 2009 and to identify patient characteristics associated with different patterns of their use in a national sample of Veterans with rheumatoid arthritis (RA). Design A retrospective cohort study. Settings Administrative databases of the USA Department of Veterans Affairs. Participants An incident cohort of 13 254 patients with newly diagnosed RA was identified. Primary outcome measures Trends and choice of DMARDs and biological agents’ usage, and time intervals between RA diagnosis and treatment Results Methotrexate use as first-line agent increased from 39.9% to 57.2% over the study period (p<0.001). Although biological dispensations increased over other DMARDs and biological agents, from 3.4% to 25% from 1999 to 2009, the percentage of RA patients diagnosed between 1999 and 2007 who had biologics dispensations remained steady at 23.3–26.7%. Compared with Caucasian, African Americans were less likely to receive biologics (HR 0.71, 95% CI 0.63 to 0.81). Patients aged 75 and older were less likely to receive biologics than those younger than 45 (HR 0.29, 95% CI 0.23 to 0.36). The time interval between RA diagnosis and treatment with DMARDs and biological agents decreased significantly over time (median: 51 days in 1999–2001 to 28 days in 2006–2007). Conclusions Methotrexate use increased as it became the preferred first-line agent, while other traditional agents declined. Dispensation of biologics increased significantly, but the proportion of RA patients eventually given biologics stabilised below 30%. A significant shorter time between RA diagnosis and DMARD or biological agent initiation in recent years suggests improvements in quality of care. There were disproportionately lower use of biologics in certain age and ethnic groups, and further studies will be needed to elucidate these observations.

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.

Communication Outcomes of Critical Imaging Results in a Computerized Notification System

OBJECTIVE Communication of abnormal test results in the outpatient setting is prone to error. Using information technology can improve communication and improve patient safety. We standardized processes and procedures in a computerized test result notification system and examined their effectiveness to reduce errors in communication of abnormal imaging results. DESIGN We prospectively analyzed outcomes of computerized notification of abnormal test results (alerts) that providers did not explicitly acknowledge receiving in the electronic medical record of an ambulatory multispecialty clinic. MEASUREMENTS In the study period, 190,799 outpatient visits occurred and 20,680 outpatient imaging tests were performed. We tracked 1,017 transmitted alerts electronically. Using a taxonomy of communication errors, we focused on alerts in which errors in acknowledgment and reception occurred. Unacknowledged alerts were identified through electronic tracking. Among these, we performed chart reviews to determine any evidence of documented response, such as ordering a follow-up test or consultation. If no response was documented, we contacted providers by telephone to determine their awareness of the test results and any follow-up action they had taken. These processes confirmed the presence or absence of alert reception. RESULTS Providers failed to acknowledge receipt of over one-third (368 of 1,017) of transmitted alerts. In 45 of these cases (4% of abnormal results), the imaging study was completely lost to follow-up 4 weeks after the date of study. Overall, 0.2% of outpatient imaging was lost to follow-up. The rate of lost to follow-up imaging was 0.02% per outpatient visit. CONCLUSION Imaging results continue to be lost to follow-up in a computerized test result notification system that alerted physicians through the electronic medical record. Although comparison data from previous studies are limited, the rate of results lost to follow-up appears to be lower than that reported in systems that do not use information technology comparable to what we evaluated.

Notification of Abnormal Lab Test Results in an Electronic Medical Record: Do Any Safety Concerns Remain?

BACKGROUND Follow-up of abnormal outpatient laboratory test results is a major patient safety concern. Electronic medical records can potentially address this concern through automated notification. We examined whether automated notifications of abnormal laboratory results (alerts) in an integrated electronic medical record resulted in timely follow-up actions. METHODS We studied 4 alerts: hemoglobin A1c > or =15%, positive hepatitis C antibody, prostate-specific antigen > or =15 ng/mL, and thyroid-stimulating hormone > or =15 mIU/L. An alert tracking system determined whether the alert was acknowledged (ie, provider clicked on and opened the message) within 2 weeks of transmission; acknowledged alerts were considered read. Within 30 days of result transmission, record review and provider contact determined follow-up actions (eg, patient contact, treatment). Multivariable logistic regression models analyzed predictors for lack of timely follow-up. RESULTS Between May and December 2008, 78,158 tests (hemoglobin A1c, hepatitis C antibody, thyroid-stimulating hormone, and prostate-specific antigen) were performed, of which 1163 (1.48%) were transmitted as alerts; 10.2% of these (119/1163) were unacknowledged. Timely follow-up was lacking in 79 (6.8%), and was statistically not different for acknowledged and unacknowledged alerts (6.4% vs 10.1%; P =.13). Of 1163 alerts, 202 (17.4%) arose from unnecessarily ordered (redundant) tests. Alerts for a new versus known diagnosis were more likely to lack timely follow-up (odds ratio 7.35; 95% confidence interval, 4.16-12.97), whereas alerts related to redundant tests were less likely to lack timely follow-up (odds ratio 0.24; 95% confidence interval, 0.07-0.84). CONCLUSIONS Safety concerns related to timely patient follow-up remain despite automated notification of non-life-threatening abnormal laboratory results in the outpatient setting.

Surgical removal of subfoveal choroidal neovascularization in age-related macular degeneration.

OBJECTIVE To assess the results of surgical excision of subfoveal choroidal neovascularization (CNV) in patients with age-related macular degeneration (AMD). DESIGN Retrospective, interventional, noncomparative case series. PARTICIPANTS AND INTERVENTION Sixty-four consecutive patients undergoing surgical removal of AMD-related subfoveal CNV were studied. The surgical method included a small retinotomy, subretinal tissue plasminogen activator (t-PA), perfluoro-n-octane, and air-fluid exchange. MAIN OUTCOME MEASURES Final visual acuity was the main outcome measure; surgical complications and recurrence rates were also assessed. RESULTS Preoperative visual acuity ranged from 20/100 to 1/200, with a mean of 20/400. Average follow-up was 19 months. The best acuity achieved after surgery ranged from 20/20 to hand motions, with a mean of 20/200. Final visual acuity ranged from 20/50 to light perception, with a mean of 20/400. Final acuity was improved 3 or more lines in 19 eyes (30%) (median, 5 lines), stable in 27 eyes (42%), and 3 or more lines worse in 18 eyes (28%) (median, 4 lines). Factors associated with greater visual improvement included poorer initial acuity, larger CNV size, and smaller subretinal hemorrhage. Analysis of groups similar to Macular Photocoagulation Study subgroups A through D showed an average improvement of 1 line for group C (visual acuity, 20/200 or worse; CNV larger than 2 disc areas). Other preoperative, intraoperative, and postoperative factors, including recurrence and retinal detachment, did not have a significant effect on final visual outcome. CONCLUSIONS After surgical excision of AMD-related subfoveal CNV, vision improved or stabilized in the majority of patients. Surgery may be of greatest value for patients with poorer vision, larger subfoveal CNV, and minimal hemorrhage. Further evaluation of this technique should be accomplished via completion of a controlled, randomized multicenter study.

Electronic health record-based triggers to detect potential delays in cancer diagnosis

Background Delayed diagnosis of cancer can lead to patient harm, and strategies are needed to proactively and efficiently detect such delays in care. We aimed to develop and evaluate ‘trigger’ algorithms to electronically flag medical records of patients with potential delays in prostate and colorectal cancer (CRC) diagnosis. Methods We mined retrospective data from two large integrated health systems with comprehensive electronic health records (EHR) to iteratively develop triggers. Data mining algorithms identified all patient records with specific demographics and a lack of appropriate and timely follow-up actions on four diagnostic clues that were newly documented in the EHR: abnormal prostate-specific antigen (PSA), positive faecal occult blood test (FOBT), iron-deficiency anaemia (IDA), and haematochezia. Triggers subsequently excluded patients not needing follow-up (eg, terminal illness) or who had already received appropriate and timely care. Each of the four final triggers was applied to a test cohort, and chart reviews of randomly selected records identified by the triggers were used to calculate positive predictive values (PPV). Results The PSA trigger was applied to records of 292 587 patients seen between 1 January 2009 and 31 December 2009, and the CRC triggers were applied to 291 773 patients seen between 1 March 2009 and 28 February 2010. Overall, 1564 trigger positive patients were identified (426 PSA, 355 FOBT, 610 IDA and 173 haematochezia). Record reviews revealed PPVs of 70.2%, 66.7%, 67.5%, and 58.3% for the PSA, FOBT, IDA and haematochezia triggers, respectively. Use of all four triggers at the study sites could detect an estimated 1048 instances of delayed or missed follow-up of abnormal findings annually and 47 high-grade cancers. Conclusions EHR-based triggers can be used successfully to flag patient records lacking follow-up of abnormal clinical findings suspicious for cancer.

Characteristics and Predictors of Missed Opportunities in Lung Cancer Diagnosis: An Electronic Health Record–Based Study

PURPOSE Understanding delays in cancer diagnosis requires detailed information about timely recognition and follow-up of signs and symptoms. This information has been difficult to ascertain from paper-based records. We used an integrated electronic health record (EHR) to identify characteristics and predictors of missed opportunities for earlier diagnosis of lung cancer. METHODS Using a retrospective cohort design, we evaluated 587 patients of primary lung cancer at two tertiary care facilities. Two physicians independently reviewed each case, and disagreements were resolved by consensus. Type I missed opportunities were defined as failure to recognize predefined clinical clues (ie, no documented follow-up) within 7 days. Type II missed opportunities were defined as failure to complete a requested follow-up action within 30 days. RESULTS Reviewers identified missed opportunities in 222 (37.8%) of 587 patients. Median time to diagnosis in cases with and without missed opportunities was 132 days and 19 days, respectively (P < .001). Abnormal chest x-ray was the clue most frequently associated with type I missed opportunities (62%). Follow-up on abnormal chest x-ray (odds ratio [OR], 2.07; 95% CI, 1.04 to 4.13) and completion of first needle biopsy (OR, 3.02; 95% CI, 1.76 to 5.18) were associated with type II missed opportunities. Patient adherence contributed to 44% of patients with missed opportunities. CONCLUSION Preventable delays in lung cancer diagnosis arose mostly from failure to recognize documented abnormal imaging results and failure to complete key diagnostic procedures in a timely manner. Potential solutions include EHR-based strategies to improve recognition of abnormal imaging and track patients with suspected cancers.

Electronic health record-based surveillance of diagnostic errors in primary care

Background Diagnostic errors in primary care are harmful but difficult to detect. The authors tested an electronic health record (EHR)-based method to detect diagnostic errors in routine primary care practice. Methods The authors conducted a retrospective study of primary care visit records ‘triggered’ through electronic queries for possible evidence of diagnostic errors: Trigger 1: A primary care index visit followed by unplanned hospitalisation within 14 days and Trigger 2: A primary care index visit followed by ≥1 unscheduled visit(s) within 14 days. Control visits met neither criterion. Electronic trigger queries were applied to EHR repositories at two large healthcare systems between 1 October 2006 and 30 September 2007. Blinded physician–reviewers independently determined presence or absence of diagnostic errors in selected triggered and control visits. An error was defined as a missed opportunity to make or pursue the correct diagnosis when adequate data were available at the index visit. Disagreements were resolved by an independent third reviewer. Results Queries were applied to 212 165 visits. On record review, the authors found diagnostic errors in 141 of 674 Trigger 1-positive records (positive predictive value (PPV)=20.9%, 95% CI 17.9% to 24.0%) and 36 of 669 Trigger 2-positive records (PPV=5.4%, 95% CI 3.7% to 7.1%). The control PPV of 2.1% (95% CI 0.1% to 3.3%) was significantly lower than that of both triggers (p≤0.002). Inter-reviewer reliability was modest, though higher than in comparable previous studies (к=0.37 (95% CI 0.31 to 0.44)). Conclusions While physician agreement on diagnostic error remains low, an EHR-facilitated surveillance methodology could be useful for gaining insight into the origin of these errors.

Disease-Free Survival at 2 or 3 Years Correlates With 5-Year Overall Survival of Patients Undergoing Radical Cystectomy for Muscle Invasive Bladder Cancer

PURPOSE The conventional primary end point in trials of perioperative systemic therapy for muscle invasive bladder cancer is 5-year overall survival. We identified an association between disease-free survival at 2 to 3 years and 5-year overall survival. MATERIALS AND METHODS We retrospectively analyzed a multicenter database containing records of 2,724 patients treated with radical cystectomy for muscle invasive bladder cancer with negative margins. Of these patients 844 had received adjuvant chemotherapy. We evaluated the association of disease-free survival at 2 and 3 years with overall survival at 5 years using Cox proportional hazards modeling and the kappa statistic. RESULTS Overall 2-year/3-year disease-free survival was 0.63/0.57 and 5-year overall survival was 0.47. The overall agreement between 2-year disease-free survival and 5-year overall survival was 79%, and between 3-year disease-free survival and 5-year overall survival was 81%. Agreements were similar when analyzed within pathological substages, radical cystectomy decades and adjuvant chemotherapy subgroups. The kappa statistic was 0.57 (95% CI 0.53-0.60) for 2-year disease-free survival/5-year overall survival and 0.61 (95% CI 0.58-0.64) for 3-year disease-free survival/5-year overall survival, indicating moderate agreement. The hazard ratio for disease-free survival as a time dependent variable was 12.7 (95% CI 11.60-13.90), indicating a strong relationship between disease-free and overall survival. CONCLUSIONS Disease-free survival rates at 2 and 3 years correlate with and are potential intermediate surrogates for 5-year overall survival in patients treated with radical cystectomy for muscle invasive bladder cancer regardless of adjuvant chemotherapy. These data warrant external validation and may expedite the development of adjuvant systemic therapy. In addition, they may be applicable to the neoadjuvant setting.