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Obesity results from expansion of white adipose tissue. The inability of white adipose tissue to adequately store lipids leads to ectopic deposition of lipids in non-adipose tissue that can lead to systemic insulin resistance. It is well known that insulin resistance correlates with inflammation of adipose tissue in obese animals and humans. Decreasing inflammation in the adipose tissue has been proven as a therapeutic strategy for improvement of insulin sensitivity in vivo. Numerous factors secreted by immune cells, including macrophages, have been suggested as regulating adipose tissue insulin sensitivity.

In the first part of my thesis, I describe the role of one such factor, CD40 in adipose tissue inflammation. The CD40-CD40L dyad acts as co-stimulation in the interaction of antigen-presenting cells, such as macrophages and dendritic cells, with effector cells, such as T cells, in adaptive immunity. We found that CD40 knockout mice were smaller but surprisingly more insulin resistant and glucose intolerant compared to wild-type mice when fed a high fat diet. Consistent with their metabolic phenotype, knockout mice displayed increased adipose tissue inflammation with infiltration of immune cells including macrophages and T cells. Consistent with increased inflammation, CD40 knockout adipose tissue displayed decreased lipid storage. Deficiency of CD40 also led to increased lipid deposition in liver, which may be due to increased lipid release into circulation from the adipose tissue as well as increased lipid synthesis in the liver. CD40 knockout mice had increased hepatic insulin resistance and increased gluconeogensis despite decreased hepatic inflammation. These findings suggest that CD40 is a novel regulator of adipose tissue inflammation in diet-induced obesity.

In the second part of this thesis we examined perivascular adipose tissue and brown adipose tissue for the presence of inflammation. In contrast to visceral adipose tissue, macrophage infiltration was absent in perivascular and brown adipose tissue as defined by reduced F480+ cells by flow cytometry and immunohistochemistry. We also found that perivascular adipose tissue was similar to brown adipose tissue as shown by gross morphology and gene expression pattern. Inflammatory gene expression was not increased in brown or perivascular adipose tissue in obese mice as determined by microarray gene expression analysis. These findings suggest that perivascular adipose tissue is more similar to brown adipose tissue than white adipose tissue and that both perivascular and brown adipose tissue are resistant to inflammation.

We conclude that, (1) CD40 protects against adipose tissue inflammation in diet-induced obesity, (2) the CD40 knockout mouse is an interesting model of hepatic steatosis with decreased inflammation and (3) perivascular adipose tissue is almost identical to brown adipose tissue in obese mice and that both are resistant to inflammation.

Heparin-induced thrombocytopenia is a rare and serious reaction to unfractionated heparin and low-molecular-weight heparins in children. Quick recognition, discontinuation of heparin, and subsequent treatment with an alternative anticoagulant are essential steps to prevent serious complications such as thrombus and limb amputation. The purpose of this review is to describe the clinical features of heparin-induced thrombocytopenia in children and to summarize the data available for its management. This paper summarizes data and relates the use of direct thrombin inhibitors with clinical outcomes. A literature search was conducted with Ovid, using the key terms argatroban, bivalirudin, hirulog, danaparoid, lepirudin, direct thrombin inhibitor, heparin-induced thrombocytopenia, thrombosis, warfarin, and fondaparinux. Articles were excluded if they were classified as editorials, review articles, or conference abstracts or if they involved patients 18 years of age or older or described disease states not related to thrombosis. Nineteen articles containing 33 case reports were identified and evaluated for this review. Of the 33 cases, 14, 10, 4, and 2 cases described the use of lepirudin, danaparoid, argatroban, and bivalirudin, respectively. Two cases did not report the type of anticoagulant used, and 1 case used aspirin. The most commonly reported complication was bleeding.

OBJECTIVES: To understand how drug therapy differently affects older women and men.

DESIGN: Population-based, retrospective cohort study.

SETTING: Ontario, Canada.

PARTICIPANTS: Twenty-one thousand five hundred twenty-six older adults (13,760 women, 7,766 men) with dementia newly started on oral atypical antipsychotic therapy between April 1, 2007, and March 1, 2010.

MEASUREMENTS: Numbers and rates of serious events. Serious events were defined as a hospital admission or death within 30 days of treatment initiation. Unadjusted and adjusted odds ratios of women and men were compared in the full cohort and in strata based on setting of care, age, Charlson Comorbidity Index (CCI), and antipsychotic dose.

RESULTS: Of 21,526 older adults with a median age of 84, 1,889 (8.8%) had a serious event (1,044 women, 7.6%; 845 men, 10.9%). Of these, 363 women (2.6%) and 355 men (4.6%) died. Men were more likely than women to be hospitalized or die during the 30-day follow-up period (adjusted odds ratio = 1.47, 95% confidence interval = 1.33-1.62) and consistently more likely to experience a serious event in each stratum. A gradient of risk according to drug dose was found for the development of a serious event in women and men.

CONCLUSION: The risk of developing a serious event shortly after the initiation of antipsychotic therapy was high in women and men with dementia but was consistently higher in older men. This pattern remained the same in strata based on setting of care, age, CCI, and antipsychotic dose. Geriatrics Society.

PURPOSE: To validate an algorithm that uses delivery date and diagnosis codes to define gestational age at birth in electronic health plan databases.

METHODS: Using data from 225 384 live born deliveries to women aged 15-45 years in 2001-2007 within eight of the 11 health plans participating in the Medication Exposure in Pregnancy Risk Evaluation Program, we compared (1) the algorithm-derived gestational age versus the "gold-standard" gestational age obtained from the infant birth certificate file and (2) the prenatal exposure status of two antidepressants (fluoxetine and sertraline) and two antibiotics (amoxicillin and azithromycin) as determined by the algorithm-derived versus the gold-standard gestational age.

RESULTS: The mean algorithm-derived gestational age at birth was lower than the mean obtained from the birth certificate file among singleton deliveries (267.9 vs 273.5 days) but not among multiple-gestation deliveries (253.9 vs 252.6 days). The algorithm-derived prenatal exposure to the antidepressants had a sensitivity and a positive predictive value of >/=95%, and a specificity and a negative predictive value of almost 100%. Sensitivity and positive predictive value were both >/=90%, and specificity and negative predictive value were both >99% for the antibiotics.

CONCLUSIONS: A gestational age algorithm based upon electronic health plan data correctly classified medication exposure status in most live born deliveries, but trimester-specific misclassification may be higher for drugs typically used for short durations. Copyright (c) 2013 John Wiley and Sons, Ltd.

BACKGROUND: It is unclear whether the higher burden from colorectal cancer among blacks is due to an increased biological susceptibility.

OBJECTIVE: To determine whether non-Hispanic blacks (blacks) have a higher risk of adenoma recurrence than non-Hispanic whites (whites) after removal of colorectal adenoma.

DESIGN: Secondary analysis of the Polyp Prevention Trial (PPT) data.

SETTING: United States.

PATIENTS: Patients were 1668 self-identified whites and 153 blacks who completed the 4-year trial. Of these, 688 whites and 55 blacks enrolled in a posttrial, passive Polyp Prevention Trial Continued Follow-up Study (PPT-CFS) and underwent another colonoscopy.

MAIN OUTCOME MEASUREMENTS: Recurrence and location of the adenoma and advanced adenoma by race-ethnicity during PPT and cumulative recurrence over a mean follow-up of 8.3 years (range, 4.9-12.4 years) among PPT-CFS enrollees.

RESULTS: Blacks had similar risk of recurrence of adenoma (39.2% vs 39.4%; incidence risk ratio [RR] = .98; 95% CI, .80-1.20) and advanced adenoma (8.5% vs 6.4%; RR = 1.18; 95% CI, .68-2.05) as whites at the end of PPT. Recurrence risk did not differ by colon subsite. Among PPT-CFS enrollees, the cumulative recurrence rate over a maximal follow-up period of 12 years was similar for blacks and whites for adenoma (67.3% vs 67.0%; RR = 1.01; 95% CI, .84-1.21) and advanced adenoma (14.5% vs 16.9%; RR = 1.03; 95% CI, .60-1.79). LIMITATION: There were few blacks in the long-term follow-up study.

CONCLUSIONS: Adenoma and advanced adenoma recurrence did not differ by race. Our study does not support more frequent surveillance colonoscopies for blacks with a personal history of adenoma as an intervention to reduce colorectal cancer disparity. Mosby, Inc. All rights reserved.

OBJECTIVE: To describe factors that influence parent-clinician partnerships in information exchange and shared decision making (SDM) when children with special health care needs are referred to subspecialists.

METHODS: We conducted focus groups with parents of children with special health care needs and pediatric primary care and subspecialty clinicians about how to include parents as partners in information exchange and SDM. Five parent and 5 clinician groups were held to identify themes to inform the development of interventions to promote parent partnerships; evaluate a prototype referral care plan and related parent supports as one example of a partnership tool; and compare the views of parents and clinicians. We used investigator triangulation and member checking to improve validity.

RESULTS: Nineteen parents and 23 clinicians participated. Parents discussed partnerships more easily than clinicians did, though clinicians offered more ideas as sessions progressed. Parents and clinicians agreed on the importance of 3-way communication and valued primary care involvement in all stages of referral and consultation. SDM was seen by all as important; clinicians cited difficulties inherent in discussing unclear options, while parents cited insufficient information as a barrier to understanding. Use of a brief referral care plan, with parent coaching, was embraced by all parents and most clinicians. Clinicians cited time pressures and interference with work flow as potential barriers to its use.

CONCLUSIONS: Parents and clinicians endorse partnership in referrals, though relatively greater enthusiasm from parents may signal the need for work in implementing this partnership. Use of a care plan to support parent engagement appears promising as a partnership tool.

Copyright © 2013 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.

Comment on: The essential and potentially inappropriate use of antipsychotics across income groups: an analysis of linked administrative data. [Can J Psychiatry. 2012]

To evaluate the prevalence, trends, timing and duration of exposure to antiviral medications during pregnancy within a US cohort of pregnant women and to evaluate the proportion of deliveries with a viral infection diagnosis among women given antiviral medication during pregnancy. Live-born deliveries between 2001 and 2007, to women aged 15-45 years, were included from the Medication Exposure in Pregnancy Risk Evaluation Program, a collaborative research program between the U.S. Food and Drug Administration and eleven health plans. They were evaluated for prevalence, timing, duration, and temporal trends of exposure to antiviral medications during pregnancy. We also calculated the proportion of deliveries with a viral infection diagnosis among those exposed to antiviral medications. Among 664,297 live births, the overall prevalence of antiviral exposure during pregnancy was 4 % (n = 25,155). Between 2001 and 2007, antiviral medication exposure during pregnancy doubled from 2.5 to 5 %. The most commonly used antiviral medication was acyclovir, with 3 % of the deliveries being exposed and most of the exposure occurring after the 1st trimester. Most deliveries exposed to antiviral medications were exposed for less than 30 days (2 % of all live births). Forty percent of the women delivering an infant exposed to antiviral medications had a herpes diagnosis. Our findings highlight the increased prevalence of women delivering an infant exposed to antiviral medications over time. These findings support the need for large, well-designed studies to assess the safety and effectiveness of these medications during pregnancy.

OBJECTIVE: To explore young people's understanding of the differences between Chlamydia, HIV, and AIDS.

METHODS. Participants from a hospital-based adolescent clinic completed a self-administered written survey. Three questions assessed participants' understanding of the differences between Chlamydia, HIV, and AIDS.

RESULTS: Nearly half of the 119 participants selected "No" or "Don't know" when asked if there are differences between Chlamydia and HIV and between HIV and AIDS. Increasing age was associated with correct response.

CONCLUSIONS: A large proportion of youth in this sample did not know that there are differences between Chlamydia, HIV, and AIDS. Previous research suggests that some young people are afraid to be screened for Chlamydia because they fear that a Chlamydia diagnosis has the same ramifications as an AIDS diagnosis. Findings from this study indicate that more education about the differences between Chlamydia, HIV, and AIDS is needed.

Little is known about dental case managers as few programs have been scientifically evaluated. The goal of this study was to explore the impact of dental case manager on retention in dental care and completion of treatment plans, while specifically exploring the number of dental case manager encounters. Fourteen programs enrolled people with HIV/AIDS (PLWHA) in dental care and a longitudinal study between 2007 and 2009. The 758 participants had a total of 2715 encounters with a dental case manager over twelve months: 29% had a single encounter; 21% had two; 27% had 3-4 and; 23% had 5-29 encounters. Adjusting for baseline characteristics, participants receiving more encounters were significantly more likely to complete their Phase 1 treatment plan, be retained in dental care, and experience improvements in overall oral health status. Organizations considering efforts to improve the oral health of vulnerable, hard-to-engage populations should consider these findings when planning interventions.

BACKGROUND: Overuse of unnecessary medications in frail older adults with limited life expectancy remains an understudied challenge.

OBJECTIVE: To identify intervention studies that reduced use of unnecessary medications in frail older adults. A secondary goal was to identify and review studies focusing on patients approaching end of life. We examined criteria for identifying unnecessary medications, intervention processes for medication reduction, and intervention effectiveness.

METHODS: A systematic review of English articles using MEDLINE, EMBASE, and International Pharmaceutical Abstracts from January 1966 to September 2012. Additional studies were identified by searching bibliographies. Search terms included prescription drugs, drug utilization, hospice or palliative care, and appropriate or inappropriate. A manual review of 971 identified abstracts for the inclusion criteria (study included an intervention to reduce chronic medication use; at least 5 participants; population included patients aged at least 65 years, hospice enrollment, or indication of frailty or risk of functional decline-including assisted living or nursing home residence, inpatient hospitalization) yielded 60 articles for full review by 3 investigators. After exclusion of review articles, interventions targeting acute medications, or studies exclusively in the intensive care unit, 36 articles were retained (including 13 identified by bibliography review). Articles were extracted for study design, study setting, intervention description, criteria for identifying unnecessary medication use, and intervention outcomes.

RESULTS: The studies included 15 randomized controlled trials, 4 non-randomized trials, 6 pre-post studies, and 11 case series. Control groups were used in over half of the studies (n = 20). Study populations varied and included residents of nursing homes and assisted living facilities (n = 16), hospitalized patients (n = 14), hospice/palliative care patients (n = 3), home care patients (n = 2), and frail or disabled community-dwelling patients (n = 1). The majority of studies (n = 21) used implicit criteria to identify unnecessary medications (including drugs without indication, unnecessary duplication, and lack of effectiveness); only one study incorporated patient preference into prescribing criteria. Most (25) interventions were led by or involved pharmacists, 4 used academic detailing, 2 used audit and feedback reports targeting prescribers, and 5 involved physician-led medication reviews. Overall intervention effect sizes could not be determined due to heterogeneity of study designs, samples, and measures.

CONCLUSIONS: Very little rigorous research has been conducted on reducing unnecessary medications in frail older adults or patients approaching end of life.

PURPOSE: In post-marketing drug safety surveillance, data mining can potentially detect rare but serious adverse events. Assessing an entire collection of drug-event pairs is traditionally performed on a predefined level of granularity. It is unknown a priori whether a drug causes a very specific or a set of related adverse events, such as mitral valve disorders, all valve disorders, or different types of heart disease. This methodological paper evaluates the tree-based scan statistic data mining method to enhance drug safety surveillance.

METHODS: We use a three-million-member electronic health records database from the HMO Research Network. Using the tree-based scan statistic, we assess the safety of selected antifungal and diabetes drugs, simultaneously evaluating overlapping diagnosis groups at different granularity levels, adjusting for multiple testing. Expected and observed adverse event counts were adjusted for age, sex, and health plan, producing a log likelihood ratio test statistic.

RESULTS: Out of 732 evaluated disease groupings, 24 were statistically significant, divided among 10 non-overlapping disease categories. Five of the 10 signals are known adverse effects, four are likely due to confounding by indication, while one may warrant further investigation.

CONCLUSION: The tree-based scan statistic can be successfully applied as a data mining tool in drug safety surveillance using observational data. The total number of statistical signals was modest and does not imply a causal relationship. Rather, data mining results should be used to generate candidate drug-event pairs for rigorous epidemiological studies to evaluate the individual and comparative safety profiles of drugs.

Copyright (c) 2013 John Wiley and Sons, Ltd.

BACKGROUND: Tools for the prediction of atrial fibrillation (AF) may identify high-risk individuals more likely to benefit from preventive interventions and serve as a benchmark to test novel putative risk factors.

METHODS AND RESULTS: Individual-level data from 3 large cohorts in the United States (Atherosclerosis Risk in Communities [ARIC] study, the Cardiovascular Health Study [CHS], and the Framingham Heart Study [FHS]), including 18 556 men and women aged 46 to 94 years (19% African Americans, 81% whites) were pooled to derive predictive models for AF using clinical variables. Validation of the derived models was performed in 7672 participants from the Age, Gene and Environment-Reykjavik study (AGES) and the Rotterdam Study (RS). The analysis included 1186 incident AF cases in the derivation cohorts and 585 in the validation cohorts. A simple 5-year predictive model including the variables age, race, height, weight, systolic and diastolic blood pressure, current smoking, use of antihypertensive medication, diabetes, and history of myocardial infarction and heart failure had good discrimination (C-statistic, 0.765; 95% CI, 0.748 to 0.781). Addition of variables from the electrocardiogram did not improve the overall model discrimination (C-statistic, 0.767; 95% CI, 0.750 to 0.783; categorical net reclassification improvement, -0.0032; 95% CI, -0.0178 to 0.0113). In the validation cohorts, discrimination was acceptable (AGES C-statistic, 0.664; 95% CI, 0.632 to 0.697 and RS C-statistic, 0.705; 95% CI, 0.664 to 0.747) and calibration was adequate.

CONCLUSION: A risk model including variables readily available in primary care settings adequately predicted AF in diverse populations from the United States and Europe.

BACKGROUND: Ambulatory care sensitive hospitalizations (ACSHs) are commonly used as measures of access to and quality of care. They are defined as hospitalizations for certain acute and chronic conditions; yet, they are most commonly used in analyses comparing different groups without adjustment for individual-level comorbidity. We present an exploration of their roles in predicting ACSHs for acute and chronic conditions.

METHODS: Using 1998-99 US Medicare claims for 1 06 930 SEER-Medicare control subjects and 1999 Area Resource File data, we modelled occurrence of acute and chronic ACSHs with logistic regression, examining effects of different predictors on model discriminatory power.

RESULTS: Flags for the presence of a few comorbid conditions-congestive heart failure, chronic obstructive pulmonary disease, diabetes, hypertension and, for acute ACSHs, dementia-contributed virtually all of the discriminative ability for predicting ACSHs. C-statistics were up to 0.96 for models predicting chronic ACSHs and up to 0.87 for predicting acute ACSHs. C-statistics for models lacking comorbidity flags were lower, at best 0.73, for both acute and chronic ACSHs.

CONCLUSION: Comorbidity is far more important in predicting ACSH risk than any other factor, both for acute and chronic ACSHs. Imputations about quality and access should not be made from analyses that do not control for presence of important comorbid conditions. Acute and chronic ACSHs differ enough that they should be modelled separately. Unaggregated models restricted to persons with the relevant diagnoses are most appropriate for chronic ACSHs.

Background/Aims: Colonoscopy may be less effective in preventing cancer in the proximal colon. We evaluated whether risk factors for adenoma recurrence exhibit differential effect on adenoma recurrence by colon subsite.

Methods: We examined the association of age, sex, body mass index, smoking status and use of nonsteroidal anti-inflammatory drugs (NSAIDs) on proximal and distal adenoma recurrence among 1,864 participants in the Polyp Prevention Trial. We used multinomial logistic regression models to calculate the relative risk ratios (RRR) and 95% CI.

Results: 733 (39.3%) participants had adenoma recurrence (228 distal only, 369 proximal only and 136 synchronous proximal and distal adenoma). When compared to participants without adenoma recurrence, no factor was associated with an increased risk of distal only adenoma recurrence. Age 65-69 years (RRR = 1.47, 95% CI 1.00-2.16), age >/=70 years (RRR = 2.24, 95% CI 1.57-3.20), and male sex (RRR = 1.73, 95% CI 1.32-2.27) were positively associated with proximal only adenoma recurrence. NSAIDs use was associated with a reduced risk of adenoma recurrence by similar magnitude in distal (RRR = 0.78, 95% CI 0.58-1.07) and proximal colon (RRR = 0.77, 95% CI 0.60-1.00).

Conclusions: We did not find any modifiable risk factor that differentially increases proximal as compared to distal adenoma recurrence to be clinically useful for targeted intervention.

OBJECTIVE: Few studies based in well-defined North American populations have examined the occurrence of juvenile idiopathic arthritis (JIA), and none has been based in an ethnically diverse population. We used computerized healthcare information from the Kaiser Permanente Northern California membership to validate JIA diagnoses and estimate the incidence and prevalence of the disease in this well-characterized population.

METHODS: We identified children aged /= 1 relevant International Classification of Diseases, 9th edition, diagnosis code of 696.0, 714, or 720 in computerized clinical encounter data during 1996-2009. In a random sample, we then reviewed the medical records to confirm the diagnosis and diagnosis date and to identify the best-performing case-finding algorithms. Finally, we used the case-finding algorithms to estimate the incidence rate and point prevalence of JIA.

RESULTS: A diagnosis of JIA was confirmed in 69% of individuals with at least 1 relevant code. Forty-five percent were newly diagnosed during the study period. The age- and sex-standardized incidence rate of JIA per 100,000 person-years was 11.9 (95% CI 10.9-12.9). It was 16.4 (95% CI 14.6-18.1) in girls and 7.7 (95% CI 6.5-8.9) in boys. The peak incidence rate occurred in children aged 11-15 years. The prevalence of JIA per 100,000 persons was 44.7 (95% CI 39.1-50.2) on December 31, 2009.

CONCLUSION: The incidence rate of JIA observed in the Kaiser Permanente population, 1996-2009, was similar to that reported in Rochester, Minnesota, USA, but 2 to 3 times higher than Canadian estimates.

BACKGROUND: Atrial fibrillation (AF) is a strong risk factor for heart failure (HF); HF onset in patients with AF is associated with increased morbidity and mortality. Risk factors that predict HF in individuals with AF in the community are not well established.

METHODS AND RESULTS: We examined clinical variables related to the 10-year incidence of HF in 725 individuals (mean 73.3 years, 45% women) with documented AF in the Framingham Heart Study. Event rates for incident HF (n = 161, 48% in women) were comparable in women (4.30 per 100 person-years) and men (3.34 per 100 person-years). Age, body mass index, ECG LV hypertrophy, diabetes, significant murmur, and history of myocardial infarction were positively associated with incident HF in multivariable models (C-statistic 0.71; 95% confidence interval 0.67-0.75). We developed a risk algorithm for estimating absolute risk of HF in AF patients with good model fit and calibration (adjusted calibration chi2 statistic 7.29; Pchi2 = 0.61). Applying the algorithm, 47.6% of HF events occurred in the top tertile in men compared with 13.1% in the bottom tertile, and 58.4% in women in the upper tertile compared with 18.2% in the lowest category. For HF type, women had a non-significantly higher incidence of HF with preserved EF compared with men.

CONCLUSIONS: We describe advancing age, LV hypertrophy, body mass index, diabetes, significant heart murmur, and history of myocardial infarction as clinical predictors of incident HF in individuals with AF. A risk algorithm may help identify individuals with AF at high risk of developing HF.

PURPOSE: Research on medication safety in pregnancy often utilizes health plan and birth certificate records. This study discusses methods used to link mothers with infants, a crucial step in such research.

METHODS: We describe how eight sites participating in the Medication Exposure in Pregnancy Risk Evaluation Program created linkages between deliveries, infants and birth certificates for the 2001-2007 birth cohorts. We describe linkage rates across sites, and for two sites, we compare the characteristics of populations linked using different methods.

RESULTS: Of 299 260 deliveries, 256 563 (86%; range by site, 74-99%) could be linked to infants using a deterministic algorithm. At two sites, using birth certificate data to augment mother-infant linkage increased the representation of mothers who were Hispanic or non-White, younger, Medicaid recipients, or had low educational level. A total of 236 460 (92%; range by site, 82-100%) deliveries could be linked to a birth certificate.

CONCLUSIONS: Tailored approaches enabled linking most deliveries to infants and to birth certificates, even when data systems differed. The methods used may affect the composition of the population identified. Linkages established with such methods can support sound pharmacoepidemiology studies of maternal drug exposure outside the context of a formal registry. Copyright (c) 2013 John Wiley and Sons, Ltd.

Objective. We sought to examine primary care providers' gout knowledge and reported treatment patterns in comparison with current treatment recommendations.

Methods. We conducted a national survey of a random sample of US primary care physicians to assess their treatment of acute, intercritical and tophaceous gout using published European and American gout treatment recommendations and guidelines as a gold standard.

Results. There were 838 respondents (response rate of 41%), most of whom worked in private practice (63%) with >16 years experience (52%). Inappropriate dosing of medications in the setting of renal disease and lack of prophylaxis when initiating urate-lowering therapy (ULT) accounted for much of the lack of compliance with treatment recommendations. Specifically for acute podagra, 53% reported avoidance of anti-inflammatory drugs in the setting of renal insufficiency, use of colchicine at a dose of ≤2.4 mg/day and no initiation of a ULT during an acute attack. For intercritical gout in the setting of renal disease, 3% would provide care consistent with the recommendations, including initiating a ULT at the appropriate dose with dosing titration to a serum urate level of ≤6 mg/dl and providing prophylaxis. For tophaceous gout, 17% reported care consistent with the recommendations, including ULT use with dosing titration to a serum urate level of ≤6 mg/dl and prophylaxis.

Conclusion. Only half of primary care providers reported optimal treatment practices for the management of acute gout and <20% for intercritical or tophaceous gout, suggesting that care deficiencies are common.

OBJECTIVE: As home medication use increases, medications previously managed by nurses are now managed by patients and their families. Our objective was to describe the types of errors occurring in the home medication management of children with cancer.

METHODS: In a prospective observational study at 3 pediatric oncology clinics in the northeastern and southeastern United States, patients undergoing chemotherapy and their parents were recruited from November 2007 through April 2011. We reviewed medical records and checked prescription doses. A trained nurse visited the home, reviewed medication bottles, and observed administration. Two physicians independently made judgments regarding whether an error occurred and its severity. Overall rates of errors were weighted to account for clustering within sites.

RESULTS: We reviewed 963 medications and observed 242 medication administrations in the homes of 92 patients. We found 72 medication errors. Four errors led to significant patient injury. An additional 40 errors had potential for injury: 2 were life-threatening, 13 were serious, and 25 were significant. Error rates varied between study sites (40-121 errors per 100 patients); the weighted overall rate was 70.2 errors per 100 patients (95% confidence interval [CI]: 58.9-81.6). The weighted rate of errors with injury was 3.6 (95% CI: 1.7-5.5) per 100 patients and with potential to injure the patient was 36.3 (95% CI: 29.3-43.3) per 100 patients. Nonchemotherapy medications were more often involved in an error than chemotherapy.

CONCLUSIONS: Medication errors were common in this multisite study of outpatient pediatric cancer care. Rates of preventable medication-related injuries in this outpatient population were comparable or higher than those found in studies of hospitalized patients.