De-identified Information Research Articles

A Protocol for the Pharmacokinetics of Enteric Coated Mycophenolate Sodium in Lupus Nephritis (POEMSLUN): an open-label, randomised controlled trial

IntroductionMycophenolate sodium, an enteric-coated tablet (EC-MPS), is as effective and safe as mycophenolate mofetil (MMF) in preventing transplant rejection. EC-MPS and MMF improve the outcome of severe lupus nephritis (LN)...

Patient-Level Medication Regimen Complexity Across Populations With Chronic Disease

BackgroundExpected treatment effectiveness from medications can be diminished due to suboptimal adherence. Medication nonadherence has been linked to pill burden from the quantity of medications; however, medication regimens with similar quantities of medications vary in complexity due to multiple dosage forms, frequency of dosing, and additional usage directions. Thus, a simple medication count ignores medication regimen complexity, especially as it pertains to a patient-level perspective that includes prescription and over-the-counter medications. A gap exists in the study of a patient-level medication regimen complexity metric across disease-specific populations. ObjectiveThe goal of this study was to implement the quantitative Medication Regimen Complexity Index (MRCI) at the patient level in defined populations with chronic disease (geriatric depression, HIV, diabetes mellitus, and hypertension). Patient-level medication regimen complexity included all prescribed medications and over-the-counter medications documented in the electronic medication list. MethodsUsing electronic medical records at the University of Colorado Hospital ambulatory clinics, we sampled 4 retrospective cohorts of adult patients in active care in 2011 with a qualifying medical diagnosis and prescribed disease-specific medication. Samples were randomly selected from all qualifying patients; de-identified information was coded using the MRCI. ResultsCohort-defining disease-specific prescription medications (eg, antidepressants for the depression-defined cohort) contributed <20% to the total patient-level complexity MRCI score; the MRCI score was dominated by complexity associated with all other prescription medications. Within disease-specific cohorts, MRCI scores differentiated patients with the highest and lowest medication counts, comorbidity counts, and the Charlson comorbidity index scores. For example, geriatric depression patients had a highest quartile mean MRCI score of 41 and a lowest quartile mean MRCI score of 13. Between disease-specific cohorts, high and low MRCI scores differed because each cohort had its own MRCI ranges. For example, highest quartile MRCI scores varied from a mean MRCI score of 41 (geriatric depression) to 30 (hypertension); lowest quartile scores ranged from a mean MRCI score of 7 (hypertension and HIV) to 13 (geriatric depression). ConclusionsMRCI components of dosing frequency and prescribed medications outside of the cohort-defining disease medications contributed the most to the patient-level scores. Thus, chronic disease management programs may want to consider all medications that patients are taking and examine ways to reduce complexity, such as reducing multiple dosing frequencies when possible. MRCI scores differentiated high and low patient-level complexity measures, representing possible utility as a prospective tool to identify target patients for intervention. Future work includes simplifying the MRCI and enhancing the scores with medication risk factors, as well as explicitly linking to adherence and health services.

Comparison of Disease Outcomes for Patients with Chronic Myelogenous Leukemia in Chronic Phase Switched to Nilotinib or Dasatinib As Second-Line Therapy.

AbstractAbstract 2796 Background:Nilotinib and dasatinib are two tyrosine kinase inhibitors (TKIs) commonly used for the treatment of patients with chronic myelogenous leukemia in chronic phase (CML-CP) who are resistant or intolerant to imatinib. Both TKIs have been shown to be more potent than imatinib. However, no head-to-head clinical trials have been conducted comparing the efficacy of nilotinib to dasatinib as 2nd-line therapy for CML-CP patients resistant or intolerant to imatinib. This study compared disease outcomes of patients treated in the community who were switched from imatinib to 2nd-line nilotinib or dasatinib. Methods:Through an online chart abstraction form, participating community physicians submitted de-identified information on CML-CP patients ≥ 18 years old who switched after 10/28/2007 from imatinib to 2nd-line nilotinib or dasatinib with at least 30 days of follow-up. When multiple patients met the selection criteria, up to 8 patients in each group were selected randomly by physicians. Patients enrolled in clinical trials or with concurrent malignancies were excluded. Information was collected on demographics, clinical characteristics, cytogenetic response, progression to accelerated phase or blast crisis, and death from any cause. Documented complete cytogenetic response (CCyR) at a particular time point was defined as 0% Philadelphia chromosome positive cells on cytogenetic testing; patients with missing tests at that time point were counted as non-responders. Disease progression to accelerated phase or blast crisis, progression-free survival, and overall survival were compared using multivariate Cox proportional hazards models, adjusting for potential confounding factors, including patient demographics and clinical characteristics at the time the patient switched to a 2nd-line TKI. Results:122 hematologists and oncologists provided information on 597 patients, including 301 patients on nilotinib and 296 patients on dasatinib. The median follow-up was 11 months for nilotinib patients and 10 months for dasatinib patients. Age, sex, race, comorbidities, and other clinical characteristics were similar for both groups, except that nilotinib patients were more likely than dasatinib patients to have switched due to secondary imatinib resistance (p=0.047) and were less likely to have switched due to imatinib intolerance (p=0.024). Nilotinib patients had similar rates of documented CCyR compared to dasatinib patients at 12 months (37% vs. 35%, p=0.54), 24 months (42% vs. 40%, p=0.62), and 36 months (44% vs. 44%, p=0.95) following the switch. However, nilotinib patients had lower risk of progression (p=0.004), higher progression free survival (p=0.023) and a trend towards prolonged overall survival (p=0.067), adjusting for potential confounders. The table below summarizes these results. Conclusions:Among patients with CML-CP switched to nilotinib or dasatinib for 2nd-line therapy, nilotinib patients had significantly lower rates of progression and longer progression-free survival compared to dasatinib patients.OutcomeNilotinib EventsDasatinib EventsUnadjusted Hazard RatioP-valueAdjusted Hazard RatioP-value(n=301)(n=296)Progression5 (1.7)13 (4.4)0.39 (0.14–1.09)0.0720.15 (0.04–0.55)0.004Progression-free Survival286 (95.0)269 (90.9)1.81 (0.96–3.40)0.0672.14 (1.11–4.12)0.023Overall Survival291 (96.7)279 (94.3)1.71 (0.78–3.75)0.1772.13 (0.95–4.78)0.067 Disclosures:Griffin:Novartis: Consultancy, Research Funding. Guerin:Analysis Group, Inc.: Consultancy, Employment, I am an employee of Analysis Group, Inc, which has received consulting fees from Novartis Pharmaceuticals Other, Research Funding. Chen:Novartis Oncology: Employment, Own stock in Novartis Other. Macalalad:Analysis Group, Inc.: Consultancy, Employment, I am an employee of Analysis Group, Inc, which has received consulting fees from Novartis Pharmaceuticals Other, Research Funding. Luo:Analysis Group, Inc.: Consultancy, Employment, I am an employee of Analysis Group, Inc, which has received consulting fees from Novartis Pharmaceuticals Other, Research Funding. Wu:Analysis Group, Inc.: Consultancy, Employment, I am an employee of Analysis Group, Inc, which has received consulting fees from Novartis Pharmaceuticals Other, Research Funding.

Comparison of Treatment Changes for Patients with Chronic Myelogenous Leukemia in Chronic Phase Switched From Imatinib to Nilotinib or Dasatinib As Second-Line Therapy

AbstractAbstract 4443 Background:Nilotinib and dasatinib are two therapies approved by the US Food and Drug Administration for pts with Philadelphia chromosome positive chronic myelogenous leukemia in chronic phase (Ph+ CML-CP) who are resistant or intolerant to 1st-line imatinib. Although these therapies were shown to be generally effective and tolerable, sometimes they are not, requiring treatment changes (e.g., discontinuation, dose modification, and drug holidays). To date, no head-to-head study has been conducted to compare treatment changes between 2nd-line nilotinib and dasatinibin clinical practice. Methods:Through an online chart abstraction form, participating community physicians retrospectively submitted de-identified information on Ph+ CML-CP pts ≥ 18 years old who switched after 10/28/2007 from imatinib to 2nd-line nilotinib or dasatinibwith at least 30 days of follow-up. When multiple pts met the selection criteria, pts were selected randomly by physicians. Pts enrolled in clinical trials or with concurrent malignancies were excluded. Information was collected on clinical characteristics and therapy changes in 2nd-line treatment, including dose modification (increase or decrease), drug holiday, and discontinuation of current therapy with or without switch to a 3rd-line therapy. Reasons for therapy changes were also collected, and treatment changes were classified as due to (1) lack of effectiveness if reasons included progression to accelerated phase or blast crisis, failure to achieve satisfactory response, or loss of satisfactory response; (2) intolerance if reasons included adverse events; (3) other reasons, including non-adherence, vacation, pregnancy, or economic reasons. Rates of treatment changes were compared between treatment groups using chi-square tests. Results:122 hematologists and oncologists provided information on 597 pts (301 nilotinib pts and 296 dasatinib pts). The median follow-up was 11 months (range 1–54 months) for pts on nilotinib and 10 months (range 1–56 months) for those on dasatinib. The two groups had similar age, sex, race, and comorbidities. Overall, treatment change was infrequent for both nilotinib and dasatinib patients (10% vs. 13%, p=0.40), but nilotinib pts had significantly fewer dose increases vs. dasatinib pts (0.0% vs. 1.4%, p=0.04), and they tended to have fewer drug holidays (1.7% vs. 4.4%, p=0.05). When treatment changes were classified by reason for change, nilotinib pts were less likely to change treatment due to lack of effectiveness vs. dasatinib pts (2.0% vs. 5.1%, p=0.04). Further, among pts who discontinued, fewer nilotinib pts discontinued due to lack of effectiveness (29% vs. 61%, p=0.03). Nilotinib and dasatinib pts had similar rates of treatment changes due to intolerance or other reasons, except for drug holiday, where nilotinib pts had fewer events than dasatinibpts (0% vs. 1.7%, p=0.02). The table below summarizes the changes in treatment by reason for treatment change. Conclusions:For Ph+ CML-CP pts on 2nd-line nilotinib or dasatinib, pts on nilotinib were less likely than those on dasatinibto change treatment due to lack of effectiveness.NilotinibDasatinibP-value(n=301)(n=296)Treatment change due to lack of effectiveness, n (%)6 (2.0)15 (5.1)0.04Discontinuation with or without switch to 3rd-line6 (2.0)14 (4.7)0.06Dose increase0 (0.0)4 (1.4)0.04Treatment change due to intolerance, n (%)11 (3.7)11 (3.7)0.97Discontinuation with or without switch to 3rd-line2 (0.7)3 (1.0)0.64Drug holiday0 (0.0)5 (1.7)0.02Dose decrease9 (3.0)3 (1.0)0.09Treatment change due to other reasons, n (%)18 (6.0)13 (4.4)0.38Discontinuation with or without switch to 3rd-line13 (4.3)6 (2.0)0.11Drug holiday5 (1.7)8 (2.7)0.38 Disclosures:Macalalad:Analysis Group, Inc.: Consultancy, Employment, I am an employee of Analysis Group, Inc, which has received consulting fees from Novartis Pharmaceuticals Other, Research Funding. Chen:Novartis Oncology: Employment, Own stock in Novartis Other. Guerin:Analysis Group, Inc.: Consultancy, Employment, I am an employee of Analysis Group, Inc, which has received consulting fees from Novartis Pharmaceuticals Other, Research Funding. Luo:Analysis Group, Inc.: Consultancy, Employment, I am an employee of Analysis Group, Inc, which has received consulting fees from Novartis Pharmaceuticals Other, Research Funding. Wu:Analysis Group, Inc.: Consultancy, Employment, I am an employee of Analysis Group, Inc, which has received consulting fees from Novartis Pharmaceuticals Other, Research Funding. Griffin:Novartis: Consultancy, Research Funding.

Characteristics of Patients with Chronic Myelogenous Leukemia in Chronic Phase Switched to Nilotinib or Dasatinib As Second-Line Therapy

AbstractAbstract 4447 Background:Since 2007, nilotinib and dasatinib have been available for 2nd-line therapy for patients with chronic myelogenous leukemia in chronic phase (CML-CP) who are resistant or intolerant to imatinib. In clinical trials, both drugs have been shown to be effective and safe, but with different side-effect profiles. Currently, little is known about the characteristics of patients who are switched to nilotinib or dasatinib in a real-world setting. Methods:Through an online chart abstraction form, participating community physicians retrospectively submitted de-identified information on CML-CP patients ≥ 18 years old who switched after 10/28/2007 from imatinib to either 2nd-line nilotinib or dasatinib and who had at least 30 days of follow-up. When multiple patients met the selection criteria, up to 8 patients from each group were selected randomly by physicians. Patients enrolled in clinical trials or with concurrent malignancies were excluded. Information on patient characteristics at the time of switching TKI therapy was collected, including age, sex, race, comorbidities, prior imatinib dosing, reasons for switching, and the dose regimen of nilotinib or dasatinib at initiation. Characteristics were compared between nilotinib and dasatinib patients using Wilcoxon and chi-square tests. Results:122 hematologists and oncologists provided information on 597 patients (301 on 2nd-line nilotinib and 296 on 2nd-line dasatinib). The table below summarizes the comparisons of the two groups. Both groups had similar age, sex, race, and comorbidity profile. Nilotinib patients were more likely than dasatinib patients to have had secondary imatinib resistance (p=0.047), more likely to have received a maximum imatinib dosing of 600 or 800 mg/day (p=0.006), and less likely to have switched due to imatinib intolerance (p=0.024). Conclusions:Patients switched to nilotinib vs. dasatinib had similar demographic and clinical characteristics at the time of switch, but nilotinib patients were more likely to have had an imatinib dose increase before the switch, and were more likely to have had secondary imatinib resistance. Patients switched to nilotinib vs. dasatinib were also less likely to have had imatinib intolerance. These findings suggest that resistance or intolerance to imatinib therapy have had more impact than patient demographics or clinical characteristics in deciding which drug to use for 2nd-line therapy.Patient characteristicsNilotinibDasatinibP-value(n=301)(n=296)Median age, years (range)60 (22, 83)60 (21, 83)0.431Male n (%)202 (67.1)189 (63.9)0.402Race, n (%)American Indian or Alaska Native7 (2.3)6 (2.0)0.803Asian16 (5.3)24 (8.1)0.172Black or African American42 (14.0)47 (15.9)0.509Hispanic or Latino26 (8.6)15 (5.1)0.085Native Hawaiian or Other Pacific Islander6 (2.0)4 (1.4)0.541White203 (67.4)201 (67.9)0.904Median CML duration, months (range)15 (1,101)13 (1,100)0.110Selected comorbidities, n (%)CML only166 (55.1)159 (53.7)0.725Cardiovascular disease including myocardial infarction, congestive heart failure and peripheral vascular disease42 (14.0)37 (12.5)0.600Dementia4 (1.3)8 (2.7)0.232Chronic pulmonary disease44 (14.6)35 (11.8)0.314Connective tissue disease5 (1.7)10 (3.4)0.180Peptic ulcer disease25 (8.3)30 (10.1)0.440Moderate or severe renal disease7 (2.3)5 (1.7)0.580Cerebrovascular disease with mild or no residual TIA3 (1.0)3 (1.0)0.984Liver disease12 (4.0)17 (5.7)0.318Diabetes36 (12.0)32 (10.8)0.659Other6 (2.0)13 (4.4)0.095Highest imatinib dose, n (%)<400 mg/day154 (51.2)183 (61.8)0.006401-600 mg/day81 (26.9)69 (23.3)601-800 mg/day66 (21.9)44 (14.9)Reason for the switch to a second-line TKI, n (%)Primary imatinib resistance122 (40.5)116 (39.2)0.738Secondary imatinib resistance105 (34.9)81 (27.4)0.047Adverse events or intolerance of imatinib67 (22.3)90 (30.4)0.024Patient not adherent to imatinib3 (1.0)6 (2.0)0.302Other[1]4 (1.3)3 (1.0)0.720[1]Notes: [1] Other reasons for switching from nilotinib included ‘patient's request’ (2), ‘recurrent disease', and ‘data suggest improved efficacy'; from dasatinib, ‘high Sokal score', ‘suboptimal cytogenetic response' and ‘patient compliance'. Disclosures:Macalalad:Analysis Group, Inc.: Consultancy, Employment, I am an employee of Analysis Group, Inc, which has received consulting fees from Novartis Pharmaceuticals Other, Research Funding. Chen:Novartis Oncology: Employment, Own stock in Novartis Other. Guerin:Analysis Group, Inc.: Consultancy, Employment, I am an employee of Analysis Group, Inc, which has received consulting fees from Novartis Pharmaceuticals Other, Research Funding. Luo:Analysis Group, Inc.: Consultancy, Employment, I am an employee of Analysis Group, Inc, which has received consulting fees from Novartis Pharmaceuticals Other, Research Funding. Wu:Analysis Group, Inc.: Consultancy, Employment, I am an employee of Analysis Group, Inc, which has received consulting fees from Novartis Pharmaceuticals Other, Research Funding. Griffin:Novartis: Consultancy, Research Funding.

Benefits of Early Switching From Imatinib to a Second-Generation Tyrosine Kinase Inhibitor Following 12 Month Complete Cytogenetic Response Failure: A Chart Review Analysis.

AbstractAbstract 2792 Background:The National Comprehensive Cancer Network (NCCN) guidelines (version 1.2013) recommend that patients with chronic myelogenous leukemia in chronic phase (CML-CP) should be tested for cytogenetic response 12 months following imatinib initiation. Failure to achieve complete cytogenetic response (CCyR) at 12 months should result in either an increased dose of imatinib (up to 800mg) or a change to a second-generation tyrosine kinase inhibitor (TKI). This study observed patients who failed to achieve CCyR at 12 months following the initiation of imatinib and compared treatment response rates and disease progression between patients who switched to a second-generation TKI early versus patients who did not. Methods:An online chart abstraction form was used to survey US oncologists and hematologists. Physicians submitted de-identified information on up to 10 adult patients with CML-CP who initiated imatinib as first line therapy (between 01/01/2007 and 26/07/2010) and failed to achieve CCyR at 12 months (between 10–14 months). Patients either switched to a second-generation TKI within 3 months following CCyR failure (early-switchers), or remained on imatinib for ≥3 months following CCyR failure (non-switchers). Non-switchers may have later switched to a second-generation TKI. The index date was defined as the date of the 12-month CCyR failure. Detailed patient information was collected, including demographics, comorbidities, imatinib dosage, and hematologic and cytogenetic response prior to the index date. Cytogenetic response and disease progression was also collected after the index date. CCyR was defined as 0% Philadelphia chromosome positive (Ph+) cells on cytogenetic testing. The proportion of patients achieving CCyR by 6, 12, and 24 months was reported among patients who had ≥1 cytogenetic test during these periods. Documented CCyR was defined as CCyR achievement analyzed among all patients, if patients were not tested for CCyR following the index date they were considered not to have achieved CCyR. Time to first documented CCyR achievement and time to disease progression were both estimated using multivariate Cox proportional hazard ratios (HR), where exposure was calculated from the index date to the first documented CCyR achievement, or to the date of progression, respectively. Multivariate regression analyses controlled for age, sex, race, index year, Charlson comorbidity index, imatinib dose and hematological response prior to index date, percentage of Ph+ cells and CML disease duration at index date, number of days between CML diagnosis and imatinib initiation, and rise in transcript level and chromosome abnormalities in Ph+ cells reported prior to the index date. Results:The majority of the 108 surveyed physicians were from a private practice (72.2%) and a small/intermediate practice size (61.1%). Physicians provided information on 593 patients who failed to achieve CCyR at 12 months; 306 were early-switchers and 287 were non-switchers. Among the non-switchers, 78 later switched to a second-generation TKI, and 104 increased imatinib dose after the index date. Patient demographics and comorbidities were similar among early-switchers and non-switchers, however, results of the 12-month cytogenetic test revealed that early-switchers had a greater number of Ph+ positive cells (51. 5 ± 16.6) compared to non-switchers (47.2 ± 13.1, p=.002). The median follow-up time was 612.5 days (range = 91–1625) and 591 days (range = 365–1623), respectively. Among patients tested for cytogenetic response during the follow-up period (274 early-switchers and 252 non-switchers), 35% of early-switchers subsequently achieved CCyR, compared to 24 % of non-switchers (p=.006). Within 6 months after the index date, 4.7% of the early-switchers achieved CCyR vs. 0.4% of non-switchers; by 12 months, 20.1% vs. 12.3% achieved CCyR; and by 24 months, 33.6% vs. 21.8% achieved CCyR, respectively (all p<.016). After adjusting for confounding factors, early-switchers had an 80% greater documented CCyR achievement rate compared to that of non-switchers (HR=1.80; p=.002) and a progression rate that was 81% lower (3.8% vs.1.5%, HR=0.19, p=.034). Conclusion:Early switching from imatinib to a second-generation TKI following 12-month CCyR failure was associated with better cytogenetic response and a lower risk of progression. Disclosures:DeAngelo:Novartis: Consultancy. Off Label Use: Everolimus in AML. Chen:Novartis Oncology: Employment, Own stock in Novartis Other. Guerin:Analysis Group, Inc.: Consultancy, Employment, I am an employee of Analysis Group, Inc, which has received consulting fees from Novartis Pharmaceuticals Other, Research Funding. Styles:Analysis Group, Inc.: Consultancy, Employment, Research Funding. Aberki:Analysis Group, Inc.: Consultancy, Employment, Research Funding. Giguere-Duval:Analysis Group, Inc.: Consultancy, Employment, Research Funding. Wu:Analysis Group, Inc.: Consultancy, Employment, I am an employee of Analysis Group, Inc, which has received consulting fees from Novartis Pharmaceuticals Other, Research Funding.

Advanced modality imaging evaluation in acute ischemic stroke may lead to delayed endovascular reperfusion therapy without improvement in clinical outcomes

PurposeAdvanced neuroimaging techniques may improve patient selection for endovascular stroke treatment but may also delay time to reperfusion. We studied the effect of advanced modality imaging with CT perfusion (CTP)...

Elevated Risk of Colorectal Neoplasia in Relatives of Patients with Colorectal Cancer: A Population-based Study in Utah

Purpose: Colorectal cancer (CRC) is the third most common cancer in the U.S. Prior studies have established that the risk of CRC is increased in first-degree relatives (FDR) of patients with CRC. Current guidelines recommend individuals with a FDR diagnosed with CRC or advanced adenoma before age 60 should undergo screening colonoscopy starting at age 40. Many of these studies rely on patient recall regarding family history and therefore lack verification of reported diagnoses. In this retrospective, population-based, case-control study we quantified the prevalence of adenomas in the relatives (FDR, second-degree-SDR or third-degree -TDR) of patients with CRC. Our study is the first population based assessment of the risk of adenomas in FDR, SDR or TDR of individuals with CRC. This study will provide evidence for or against the current screening guidelines. Methods: We performed a population-based retrospective case-control study of residents of the state of Utah, between 50 and 80 years of age, who underwent colonoscopy between February 15, 1995 and January 31, 2009 at Intermountain Healthcare or University of Utah Health System. De-identified medical information on patients undergoing colonoscopy was merged with cancer histories from the Utah Cancer Registry and overlaid on pedigrees from the Utah Population Database to investigate the familial aggregation of adenomas. Cox regression analysis was used to assess the relative risk of adenoma development in relatives. Results: There were 126,936 unique patients who underwent colonoscopy. 3,804 patients in this cohort were diagnosed with CRC and they defined the case population. For each case, one randomly selected, age- and sex-matched control was selected from the population who had CRC-free colonoscopy. The prevalence of adenomas was increased in FDRs (OR 1.82, 95% CI, 1.66-2.00), SDRs (OR 1.19, 95% CI, 1.08-1.31) and TDRs (OR 1.10, 95% CI, 1.04-1.17) of cases compared to controls. This risk was similar for FDRs whether index patients developed CRC below (OR 2.04, 95% CI: 1.74-2.39) or above 60 years old (OR 1.58, 95% CI: 1.37-1.83). Conclusion: In this study we report that FDRs, SDRs and TDRs of individuals with CRC had an increased risk of developing colorectal neoplasia themselves. The strength of the association showed a relationship based on the degree of kinship. Our data supports the current CRC screening guidelines and supports a genetic basis of inheritance for colorectal neoplasia.

Identifying and collecting pertinent medical records for centralized abstraction in a multi-center randomized clinical trial: The model used by the American College of Radiology arm of the National Lung Screening Trial

BackgroundIn clinical trials and epidemiologic studies, information on medical care utilization and health outcomes is often obtained from medical records. For multi-center studies, this information may be gathered by personnel at individual sites or by staff at a central coordinating center. We describe the process used to develop a HIPAA-compliant centralized process to collect medical record information for a large multi-center cancer screening trial. MethodsThe framework used to select, request, and track medical records incorporated a participant questionnaire with unique identifiers for each medical provider. De-identified information from the questionnaires was sent to the coordinating center indexed by these identifiers. The central coordinating center selected specific medical providers for abstraction and notified sites using these identifiers. The site personnel then linked the identifiers with medical provider information. Staff at the sites collected medical records and provided them for central abstraction. ResultsMedical records were successfully obtained and abstracted to ascertain information on outcomes and health care utilization in a study with over 18,000 study participants. Collection of records required for outcomes related to positive screening examinations and lung cancer diagnosis exceeded 90%. Collection of records for all aims was 87.32%. ConclusionsWe designed a successful centralized medical record abstraction process that may be generalized to other research settings, including observational studies. The coordinating center received no identifying data. The process satisfied requirements imposed by the Health Insurance Portability and Accountability Act and concerns of site institutional review boards with respect to protected health information.

Conversion of Chronic Pain Patients from FullOpioid Agonists to Sublingual Buprenorphine

Background: Sublingual buprenorphine-naloxone (buprenorphine SL) is a preparation that is used to treat opioid dependence. In addition, the Drug Enforcement Administration (DEA) has acknowledged the legality of an off-label use to treat pain with a sublingual buprenorphine preparation. Buprenorphine SL is unique among the opioid class of analgesics; this compound has a high affinity for the mu-receptor, yet only partially activates it. Thus, buprenorphine SL can provide analgesia, yet minimize opioid side effects. Many patients on high doses of traditional opioid medication develop tolerance. Despite escalating medication dosage, a subset of patients had a paradoxical increase in pain, which has been characterized as opioid-induced hyperalgesia (OIH). Buprenorphine SL, on the other hand, may even be anti-hyperalgesic and may have utility in treating these challenging patients. Objective: To determine the effectiveness of converting patients from traditional full agonist opioid medication to sublingual buprenorphine, as well as to identify patient groups that are most likely to benefit from this therapy. Patients who underwent conversion either had developed tolerance with diminished analgesia or were experiencing side effects on their opioid medications. Study Design: An observational report of outcomes assessment. Setting: An interventional pain management practice setting in the United States. Methods: Retrospective data from clinical records was compiled on 104 de-identified chronic pain patients whose personal information had been redacted (60 men and 44 women, aged 21-78) and who had previously been treated with opioid-agonist drugs; they were converted to buprenorphine SL in tablet form during the study. Chronic pain was defined as persistent pain for at least 6 months. Data collected from patient profiles included age, sex, diagnosis, medication history, pre-induction opioid intake, reason for detoxification, preinduction Clinical Opiate Withdrawal Score (COWS), and if applicable, cause of buprenorphine SL cessation. Pain levels and Quality of Life scores were recorded before and after conversion to buprenorphine SL. Outcome Measures: Level of analgesia for patients who continued conversion to sublingual buprenorphine for more than 2 months. Results: After initiation of buprenorphine SL therapy for more than 2 months, the mean pain scores on a scale from 0-10 decreased by 2.3 points (P &lt; 0.001). Patient Quality of Life (QoL scale) was not significantly affected by buprenorphine SL therapy (P = 0.14). The success rate was highest for patients using morphine, oxycodone, and fentanyl before buprenorphine SL induction. These patient groups had a 3.7 point decrease in pain for those taking morphine, a 2.5 point decrease in pain for those taking oxycodone, and a 2.2 point decrease for those taking fentanyl. The smallest pain reduction was seen in the patient group using oxymorphone before conversion with a 1.1 point decrease in pain. Patients taking between 100-199 mg morphine equivalent per day experienced the greatest reduction (2.7 points) in pain scores. Patients taking between 200 and 299 mg morphine equivalent before buprenorphine SL induction exhibited a decrease of over 2 points on average. Patients taking &gt; 400mg morphine equivalent reported the smallest reduction in pain scores, on average a 1.1 point decrease. Limitations: This study is limited by its observational nature. Conclusions: Patients continuing buprenorphine SL therapy for more than 60 days reported significant decreases in pain (2.3 points). Patients on doses of opioid medication between 100-199 mg morphine equivalents seemed to fare better with conversion to buprenorphine SL than patients on the highest doses (&gt; 400 mg morphine equivalents). The opioid drug used by the patient before buprenorphine SL induction appears to have some effect on buprenorphine SL conversion success. Patients previously taking morphine, oxycodone, and fentanyl had the greatest decrease in pain after conversion to buprenorphine SL. Key Words: Sublingual buprenorphine-naloxone, buprenorphine, buprenorphine SL, opioid dependence, opioid conversion, opioid-induced hyperalgesia, analgesia, full agonist opioids, opioid tolerance.

Australian triage tags: A prospective, randomised cross‐over trial and evaluation of user preference

The aim of this study was to determine if any disaster triage tag is superior to others, based on objective parameters (time, accuracy) and subjective parameters (user preference). A secondary aim was to determine the average time to perform triage assessment using 'sieve and sort'. This was a prospective, randomised cross-over trial comparing triage cards currently used, or being implemented, across Australia. De-identified patient information from a trauma database was used to create 125 cases. Volunteer participants were selected from Major Incident Medical Management and Support certified doctors, nurses, paramedics and defence medics and randomised into five groups. Participants completed timed 'sieve and sort' triage exercises on 25 different cases with each of the five triage tags and were then asked to rank the tags in order of preference. Participants also performed timed practical triage assessments (sieve and sort) on two healthy volunteers. Based on the objective measures we did not find that one card was superior to others; however, the Northern Territory card was significantly slower and less accurate (P < 0.001). Doctors were the fastest and most accurate 'sorters' (P < 0.001); however, inaccuracy was the same for all professional groups for the 'sieve'. Participants preferred the SMART card to any other tag. Participants' time to carry out a sieve was approximately 30 s, and 60 s for a sort. The SMART card was preferred by participants based on design issues, which supports its implementation. We suggest that doctors are best used in the casualty clearing post.

Erratum: Personal medicine—the new banking crisis

Nat. Biotechnol. 30, 141–147 (2012); published online 8 February 2012; corrected after print 24 February 2012 In the version of the article originally published, the citation in Figure 1 was given as ref. 14; it should be ref. 2. In Table 1, CARTaGENE was misspelled, and the descriptions in column 3of this repository, BioVu's and the International HapMap were incorrect: CARTaGENE should be described as “A repository of socio-demographic, health data and biological samples from 20,000 citizens of the province of Quebec in Canada”; BioVu's description should read “Repository of DNA samples and de-identified health information from the Vanderbilt University Medical Center's electronic system”; and the International HapMap description should read “International collaboration with the ultimate goal of developing a haplotype map of the human genome.

352 Elevated Risk of Advanced Adenomas and Colorectal Cancer in Relatives of Patients With Advanced Adenomas: A Population-Based Study in Utah

INTRODUCTION: Colorectal cancer (CRC) is the third most common cancer in the USA. Prior studies have established that the risk of CRC is increased in first-degree relatives (FDR) of patients with CRC. Current guidelines recommend individuals with a FDR diagnosed with CRC or advanced adenoma (AA) before age 60 should undergo screening colonoscopy starting at age 40. Many of these studies rely on patient recall regarding family history and therefore lack verification of reported diagnoses. In this retrospective, population-based, case-control study we quantified the prevalence of AA and CRC in the relatives (FDR, second degree-SDR or third degree-TDR) of patients with an AA. Our study is the first population based assessment of the risk of CRC and AA in FDR, SDR or TDR of individuals with an AA. This study will provide evidence for or against the current screening guidelines. METHODS: We performed a population-based retrospective case-control study of residents of the state of Utah, between 50 and 80 years of age, who underwent colonoscopy between February 15, 1995 and January 31, 2009 at Intermountain Healthcare or University of Utah Health System. De-identified medical information on patients undergoing colonoscopy was merged with cancer histories from the Utah Cancer Registry and overlaid on pedigrees from the Utah Population Database to investigate the familial aggregation of AA andCRC. Advanced adenomas were defined, for query purposes, as cases with villous histology, a snare procedure was used or the words “multiple” or “many” were used in the colonoscopy report. Cox regression analysis was used to assess the relative risk of AA and CRC development in relatives. RESULTS: There were 126,936 unique patients who underwent colonoscopy. 22,364 patients had an AA removed at colonoscopy and they defined the case population. For each case, 1 randomly selected, ageand sex-matched control was selected from the population who had AA-free colonoscopy. The prevalence of an AA was increased in FDRs (OR 1.31, 95% CI, 1.18-1.45), SDRs (OR 1.21, 95% CI, 1.1-1.33) and TDRs (OR 1.07, 95% CI, 1.01-1.13) of cases compared to controls. An elevated risk of CRC was found in probands (OR 7.64, 95% CI, 6.14-9.51) and in FDRs (RR 1.7, 95% CI: 1.46-1.98) compared to controls. However, more distant relatives (SDR/TDR) did not have a statistically elevated risk of CRC. DISCUSSION: In this study we report that FDRs, SDRs and TDRs of individuals with AA had an increased risk of developing AA themselves. The strength of the association showed a relationship based on the degree of kinship. Similarly, the risk of colorectal cancer was increased in the cases as well as in their FDRs. Our data supports the current CRC screening guidelines and raises the question of whether such screening should be extended to more distant members of the patient's family.

Third-year medical students’ knowledge of privacy and security issues concerning mobile devices

Background: The use of mobile devices are ubiquitous in medical-care professional settings, but information on privacy and security concerns of mobile devices for medical students is scarce.Aims: To gain baseline information about third-year medical students’ mobile device use and knowledge of privacy and security issues concerning mobile devices.Methods: We surveyed 67 third-year medical students at a Midwestern university on their use of mobile devices and knowledge of how to protect information available through mobile devices. Students were also presented with clinical scenarios to rate their level of concern in regards to privacy and security of information.Results: The most used features of mobile devices were: voice-to-voice (100%), text messaging (SMS) (94%), Internet (76.9%), and email (69.3%). For locking of one's personal mobile phone, 54.1% never physically lock their phone, and 58% never electronically lock their personal PDA. Scenarios considering definitely privacy concerns include emailing patient information intact (66.7%), and posting de-identified information on YouTube (45.2%) or Facebook (42.2%).Conclusions: As the ease of sharing data increases with the use of mobile devices, students need more education and training on possible privacy and security risks posed with mobile devices.

606 GENDER AND CHRONIC KIDNEY DISEASE IN PATIENTS WITH SPINA BIFIDA

INTRODUCTION AND OBJECTIVES: Children born with spina bifida are at risk for chronic kidney disease (CKD). One of the goals of urologic intervention is to prevent the compromise of kidney function. Urologic intervention can include intermittent catheterization, medications, and/or lower urinary tract reconstruction. Much debate still exists regarding risk factors for developing CKD. We evaluated the role of gender on CKD in spina bifida patients. METHODS: We retrospectively evaluated spina bifida patients using the Vanderbilt Synthetic Derivative resource. The Synthetic Derivative is a collection of de-identified information extracted from the Vanderbilt University Medical Center clinical information systems. Content is changed by deletion or permutation of all identifiers contained within each record. Study inclusion criteria were: age 10 years and ICD-9 code 741 for spina bifida confirmed with specific mention of “spina bifida” or “myelomeningocele” in the patient record. Each record was then reviewed for age, sex, race, history of dialysis, history of renal transplant, serum creatinine, history of urodynamics, and history of urological operative procedures. Glomerular filtration rate (GFR) was calculated by the Modification of Diet in Renal Disease (MDRD) study equation at 18 years of age and the Bedside Schwartz equation at 18 years of age. CKD onset was defined as GFR 60, need for dialysis, or need for renal transplant. For our analysis, we assumed that patients without serum creatinine levels and without mention of CKD in the clinical record did not have CKD. Log-rank test for equality of survivor functions was used to compare the effect of gender on CKD onset. RESULTS: We identified 1196 spina bifida patients. To decrease confounding by race, we limited our analysis to the 901 patients identified as Caucasian. Of the 901 patients, 520 had documented serum creatinine values. CKD onset occurred in 54 patients (6.0%) at an average age of 34.7 years. Male spina bifida patients were more likely to develop CKD than female spina bifida patients (p 0.03). CONCLUSIONS: In our cohort of spina bifida patients, female gender was associated with less CKD onset. Whether this gender difference is due to lifestyle factors, sex hormone effects on the kidney and or lower urinary tract or a disparity in urologic and medical care remains to be elucidated.

Cohort Profile: The Ontario HIV Treatment Network Cohort Study (OCS)

The Ontario HIV Treatment Network Cohort Study (OCS) is an observational, open dynamic cohort of people who are receiving medical care for human immunodeficiency virus (HIV) infection in Ontario, Canada. Established in the mid-1990s, the OCS has its roots in AIDS activists' demands for research that would improve the quality of life of people living with HIV while respecting their privacy. It is a collaborative and community-driven study, including a Governance Committee made up of people with HIV and other stakeholders that evaluates analysis project proposals for community relevance and ethics. From 1995 to 2010, a total of 5644 participants were enrolled and 27,720 person-years of observation were accumulated; follow-up will continue until at least 2015. In the initial years of study, the focus was on clinical data from medical chart reviews. It has since evolved into a comprehensive study that collects extensive de-identified information on clinical, laboratory and psychosocial and behavioural measures based on medical chart abstractions, interviews using a standardized questionnaire and linkage with external administrative health databases in Ontario. Interested collaborators are encouraged to submit analysis project proposals as instructed on the study website (www.ohtncohortstudy.ca).

NSW Annual Report Describing Adverse Events Following Immunisation, 2011

This report summarises Australian passive surveillance data for adverse events following immunisation in NSW for 2011. Analysis of de-identified information on all adverse events following immunisation reported to the Therapeutic Goods Administration. 449 adverse events following immunisation were reported for vaccines administered in 2011; this is slightly higher than in 2010 (n=439) and the second highest number since 2003. The most commonly reported reactions were injection site reaction, fever, allergic reaction and malaise. A large number of injection site reactions were reported following administration of the 23-valent pneumococcal polysaccharide vaccine in adults aged 65 years and over (97.4/100000 doses) and in children aged less than 7 years following administration of the 13-valent pneumococcal conjugate vaccine (29.4/100000 doses) and combined diphtheria, tetanus, pertussis (acellular) and inactivated poliovirus (quadrivalent)-containing vaccines (47.1/100000 doses). Only 10% of the reported adverse events were categorised as serious. There were two reports of death however both were attributed to causes other than vaccination. The increased number of reports in 2011 is attributable to the high rates of injection site reactions in children associated with the administration of combined diphtheria, tetanus, pertussis (acellular) and inactivated poliovirus (quadrivalent)-containing vaccines and the 13-valent pneumococcal conjugate vaccine, as well as in adults following receipt of the 23-valent pneumococcal polysaccharide vaccine.

Clinical Predictors and Institutional Variation in Home Oxygen Use in Preterm Infants

To assess home oxygen use in preterm infants, identify risk factors predicting home oxygen use, and quantify the extent of institutional variation in home oxygen use across neonatal intensive care units. We conducted a retrospective cohort analysis of surviving infants of 23- to 31-week gestational age discharged home in 2009, with de-identified electronic medical record information from the Pediatrix Clinical Data Warehouse. Mixed-effects logistic regression quantified clinical risk factors and institutional variation affecting home oxygen use. A total of 8167 infants were identified. Home oxygen use varied by gestational age, from 59% of infants 23 to 24 weeks gestational age to 7% of infants 29 to 31 weeks gestational age. Other risk factors included small for gestational age, congenital anomalies, mechanical ventilation in the first 72 hours, fraction of inhaled oxygen >0.4 in the first 72 hours, and patent ductus arteriosus. After adjusting for clinical risk factors, there was still a 4- to 5-fold difference in institutions' odds of home oxygen use. Home oxygen use was common in infants of earlier gestational ages and infants with more severe respiratory illness. Institutional variation accounted for 4- to 5-fold variation in home oxygen use. Families should be counseled about the likelihood of home oxygen use, and prospective research must identify optimal treatment strategies for high-risk infants.

Effectiveness of a Federal Healthy Start Program in Reducing the Impact of Particulate Air Pollutants on Feto-Infant Morbidity Outcomes

We sought to assess (1) the relationship between air particulate pollutants and feto-infant morbidity outcomes and (2) the impact of a Federal Healthy Start program on this relationship. This is a retrospective cohort study using de-identified hospital discharge information linked to vital records, and air pollution data from 2000 through 2007 for the zip codes served by the Central Hillsborough Federal Healthy Start Project in Tampa, Florida. Mathematical modeling was employed to compute minimal Euclidean distances to capture exposure to ambient air particulate matter. The outcomes of interest were low birth weight (LBW), very low birth weight (VLBW), small for gestational age, preterm (PTB), and very preterm birth. We used odds ratios to approximate relative risks. A total of 12,356 live births were analyzed. Overall, women exposed to air particulate pollutants were at elevated risk for LBW (AOR=1.24; 95% CI=1.07-1.43), VLBW (AOR=1.58; 95% CI=1.09-2.29) and PTB (AOR=1.18; 95% CI=1.03-1.34). Analysis by race/ethnicity revealed that the adverse effects of air particulate pollutants were most profound among black infants. Infants of women who received services provided by the Central Hillsborough Federal Healthy Start Project experienced improved feto-infant morbidity outcomes despite exposure to air particulate pollutants. Environmental air pollutants represent important risk factors for adverse birth outcomes, particularly among black women. Multi-level interventional approaches implemented by the Central Hillsborough Federal Healthy Start were found to be associated with reduced likelihood for feto-infant morbidities triggered by exposure to ambient air particulate pollutants.

Adverse Events Due to Suspected Nickel Hypersensitivity in Patients with Essure Micro-Inserts

Study Objective To review reported adverse events associated with suspected nickel hypersensitivity and subsequent clinical outcomes in patients with Essure implants and to evaluate the correlation of nickel allergy–related adverse events with positive results of nickel patch testing. Design Case series (Canadian Task Force classification II-3). Measurements and Main Results Reports of suspected nickel hypersensitivity reported from 2001 through July 21, 2010, were collected from de-identified data obtained from the MAUDE (Manufacturer and User Facility Device Experience) database and reports to the manufacturer directly from treating physicians, and published results for the 650 patients in the Phase II and Pivotal trials. Clinical outcomes and symptom resolution, when available, were obtained from de-identified information provided by the treating physicians to the manufacturer. Patients were not directly contacted for the study, and patient files were not reviewed. Patch testing was performed at the discretion of the treating physicians. Results were reported as positive or negative, without mention of the method or brand of patch testing used. Conclusion Even considering the possibility of underreporting by several orders of magnitude, the reported incidence of adverse events suspected to be related to nickel hypersensitivity in patients with Essure micro-inserts is extremely small (0.01%). The incidence of confirmed nickel reactions is even smaller. This very low incidence of clinical reactions is consistent with data from other nickel-containing implantable devices and is reassuring, raising the question of whether nickel reactions are clinically relevant in the use of nitinol-containing micro-inserts for hysteroscopic sterilization.