METHODS:   We analysed data from the Medication Exposure in Pregnancy Risk Evaluation Program (MEPREP) database, 1 January 2001 to 31 December 2007. We identified liveborn deliveries among women, aged 15-45 years on delivery date, who were members of MEPREP health plans (n=585615 deliveries). Pregnancy exposure to AEDs, determined through outpatient pharmacy dispensing files. Older AEDs were available for clinical use before 1993; other agents were considered newer AEDs. Information on sociodemographic and medical/reproductive factors was obtained from linked birth certificate files. Maternal diagnoses were identified based on ICD-9 codes.

RESULTS:   Prevalence of AED use during pregnancy increased between 2001 (15.7 per 1000 deliveries) and 2007 (21.9 per 1000 deliveries), driven primarily by a fivefold increase in the use of newer AEDs. Thirteen per cent of AED-exposed deliveries involved a combination of two or more AEDs. Psychiatric disorders were the most prevalent diagnoses, followed by epileptic and pain disorders, among AED users regardless of AED type, year of conception or gestational period.

CONCLUSIONS:   AED use during pregnancy increased between 2001 and 2007, driven by a fivefold increase in the use of newer AEDs. Nearly one in eight AED-exposed deliveries involved the concomitant use of more than one AED. Additional investigations of the reproductive safety of newer AEDs may be needed.

METHODS: Pregnancies resulting in live births were identified (N=437,950) from 2001 to 2007 among 372,543 females 12-50 years of age at delivery from 10 health maintenance organizations participating in the Medication Exposure in Pregnancy Risk Evaluation Program. Information for these descriptive analyses, including all antidiabetic medications dispensed during this period, was extracted from electronic health records and newborn birth certificates.

RESULTS: A little more than 1% (1.21%) of deliveries were to women dispensed antidiabetic medication in the 120 days before pregnancy. Use of antidiabetic medications before pregnancy increased from 0.66% of deliveries in 2001 to 1.66% of deliveries in 2007 (P<.001) because of an increase in metformin use. Most women using metformin before pregnancy had a diagnosis code for polycystic ovaries or female infertility (67.2%), whereas only 13.6% had a diagnosis code for diabetes. The use of antidiabetic medications during the second or third trimester of pregnancy increased from 2.8% of deliveries in 2001 to 3.6% in 2007 (P<.001). Approximately two thirds (68%) of women using metformin before pregnancy did not use any antidiabetic medications during pregnancy.

CONCLUSIONS: Antidiabetic medication use before and during pregnancy increased from 2001 to 2007, possibly because of increasing prevalence of gestational diabetes mellitus, type 1 and type 2 diabetes, and other conditions associated with insulin resistance.

LEVEL OF EVIDENCE: III.

METHODS: This open-label extension (OLE) study was conducted at 46 sites in the USA, Canada and Mexico. Patients completing either of two replicate randomised placebo-controlled 6-month trials received pegloticase 8 mg every 2 weeks (biweekly) or every 4 weeks (monthly). Safety was evaluated as the primary outcome, with special interest in gout flares and infusion-related reactions (IRs). Secondary outcomes included urate-lowering and clinical efficacy.

RESULTS: Patients (n=149) received a mean+/-SD of 28+/-18 pegloticase infusions and were followed for a mean of 25+/-11 months. Gout flares and IRs were the most frequently reported adverse events; these were least common in patients with a sustained urate-lowering response to treatment and those receiving biweekly treatment. In 10 of the 11 patients with a serious IR, the event occurred when uric acid exceeded 6 mg/dl. Plasma and serum uric acid levels remained /dl in most randomised controlled trial (RCT)-defined pegloticase responders throughout the OLE study and were accompanied by sustained and progressive improvements in tophus resolution and flare incidence.

CONCLUSIONS: The safety profile of long-term pegloticase treatment was consistent with that observed during 6 months of RCT treatment; no new safety signals were identified. Improvements in clinical status, in the form of flare and tophus reduction initiated during RCT pegloticase treatment in patients maintaining goal range urate-lowering responses were sustained or advanced during up to 2.5 years of additional treatment.

Methods and Results- The study cohort includes consecutive patients undergoing primary prevention ICD placement between January 1, 2006 and December 31, 2009 in 7 health plans. Baseline clinical characteristics were acquired from the National Cardiovascular Data Registry ICD Registry. Longitudinal data collection is underway, and will include hospitalization, mortality, and resource use from standardized health plan data archives. Data regarding ICD therapies will be obtained through chart abstraction and adjudicated by a panel of experts in device therapy. Compared with the populations of primary prevention ICD therapy randomized, controlled trials, the cohort (n=2621) is on average significantly older (by 2.5-6.5 years), more often female, more often from racial and ethnic minority groups, and has a higher burden of coexisting conditions. The cohort is similar, however, to a national population undergoing primary prevention ICD placement.

Conclusions- Patients undergoing primary prevention ICD implantation in this study differ from those enrolled in the randomized, controlled trials that established the efficacy of ICDs. Understanding a broad range of health outcomes, including ICD therapies, will provide patients, clinicians, and policy makers with contemporary data to inform decision-making.

METHODS: The authors previously reported a template designed to standardize urothelial diagnostic categories to enable clinicians to uniformly manage their patients. In this study, they examined the common cytomorphologic features observed in specimens diagnosed with atypical urothelial cells, cannot exclude high-grade urothelial carcinoma (AUC-H), which prove most predictive of high-grade urothelial carcinoma (HGUC).

RESULTS: The most common morphologic features observed in the AUC-H specimens were hyperchromasia, irregular nuclear borders, increased nucleus-to-cytoplasm ratio, and anisonucleosis. Of the 58 patients who had specimens diagnosed with AUC-H, 95% ultimately were diagnosed with HGUC on follow-up biopsy over the study period. The small number of patients who had AUC-H with non-HGUC follow-up did not allow for a statistical comparison to determine the predictive ability of the selected criteria for HGUC. Next, the authors used the same features to examine a subset of urine samples that were diagnosed with atypical urothelial cells of unknown significance (AUC-US) in an attempt to improve the predictive value of this clinically frustrating category. A blind review was performed of 290 urine specimens from 217 patients. In contrast to the AUC-H specimen cohort, the majority of specimens with AUC-US did not contain atypical cells with the 4 common morphologic features. All 4 features significantly predicted HGUC in surveillance patients, but not in patients with hematuria.

CONCLUSIONS: Hyperchromasia was the strongest predictor of HGUC by far in patients who were undergoing surveillance (odds ratio, 9.81). Hyperchromasia remained statistically significant in multivariate analysis, indicating its predictive strength even in the absence of other features. Cancer (Cancer Cytopathol) 2012. (c) 2012 American Cancer Society.

METHODS: According to the template, reactive/inflammatory changes were included in the negative group (no urothelial atypia or malignancy identified). The category atypical urothelial cells of undetermined significance (AUC-US) was akin to atypical squamous cells of undetermined significance (ASC-US), as was the category of atypical urothelial cells, favor high-grade carcinoma (AUC-H). The categories high-grade urothelial carcinoma (HGUC) and low-grade urothelial carcinoma also were added.

RESULTS: The Pathology Data System at the Johns Hopkins Hospital was searched for cases that met the following criteria over a period from July 1, 2007 to June 30, 2009: all cytologic specimens from the urinary tract and all surgical specimens with a diagnosis of HGUC, regardless of invasion status. All cytologic specimens were then matched with biopsies during the same period, and all surgical specimens from patients who had a cytologic diagnosis of AUC-US or AUC-H were retrieved for 18 months after the end of the 2-year study period. Greater than 50% of patients who had biopsy-confirmed HGUC had a preceding cytologic diagnosis of AUC-H or HGUC. When patients with AUC-US were added to the analysis, 80% of patients with HGUC had at least 1 abnormal urinary cytology result. Of those patients who had a diagnosis of AUC-H, 38% had urothelial cancer discovered at biopsy compared with only 10% of those with an AUC-US diagnosis.

CONCLUSIONS: The authors concluded that their template is effective in targeting those patients who need to undergo cystoscopy.

OBJECTIVE: The aim of this study was to investigate the correlates of these three adiposity biomarkers in a large community-based sample.

DESIGN, SETTING, PARTICIPANTS, AND OUTCOMES: Serum concentrations of fetuin-A, RBP4, and FABP4 were assayed in 3658 participants of the Third Generation Framingham Heart Study cohort (mean age 40 yr, 54% women). We used multivariable regression to cross-sectionally relate biomarkers to insulin resistance, cardiovascular risk factors, and the MetSyn. The genetic contribution to inter-individual variation in biomarker levels was assessed using variance-components analysis.

RESULTS: All three biomarkers exhibited sexual dimorphisms (levels higher in women for fetuin-A and FABP4 but greater in men for RBP4) and were associated positively with insulin resistance assessed using the homeostasis model, with high-sensitivity C-reactive protein, and with prevalent MetSyn (P<0.01 for all). The biomarkers showed distinct patterns of association with metabolic risk factors. RBP4 levels were correlated with body mass index only in unadjusted but not in adjusted models. None of the biomarkers were associated with prevalent diabetes in multivariable models. Circulating fetuin-A, RBP4, and FABP4 levels showed modest heritability, ranging from 15-44% (all P<0.0001).

CONCLUSIONS: In our large young- to middle-aged community-based sample, we observed that circulating levels of fetuin-A, RBP4, and FABP4 are associated with insulin resistance and with distinct components of MetSyn consistent with the multifactorial pathogenesis of metabolic dysregulation.

STUDY DESIGN AND SETTING: The nonconcurrent prospective study population consisted of 4182 patients hospitalized with AMI in central Massachusetts in four annual periods between 2001 and 2007.

RESULTS: One-quarter (25%) of patients had a DNR order written either prior to or during hospitalization. The frequency of DNR orders remained constant (24% in 2001; 26% in 2007). Among patients with DNR orders, there was a significant increase in orders written prior to hospitalization (2001: 9%; 2007: 55%). Older patients and those with a medical history of heart failure or myocardial infarction were more likely to have prior DNR orders than respective comparison groups. Patients with prior DNR orders were less likely to die 1 month after hospitalization than patients whose DNRs were written during hospitalization.

CONCLUSION: Although the use of DNR orders in patients hospitalized with AMI was stable during the period under study, in more recent years, patients are increasingly being hospitalized with DNR orders already in place.

OBJECTIVE: To test the hypothesis that a smartphone-based application could detect an irregular pulse from AF.

METHODS: Seventy-six adults with persistent AF were consented for participation in our study. We obtained pulsatile time series recordings before and after cardioversion using an iPhone 4S camera. A novel smartphone application conducted real-time pulse analysis using 2 statistical methods: root mean square of successive RR difference (RMSSD/mean) and Shannon entropy (ShE). We examined the sensitivity, specificity, and predictive accuracy of both algorithms using the 12-lead electrocardiogram as the gold standard.

RESULTS: RMSDD/mean and ShE were higher in participants in AF than in those with sinus rhythm. The 2 methods were inversely related to AF in regression models adjusting for key factors including heart rate and blood pressure (beta coefficients per SD increment in RMSDD/mean and ShE were-0.20 and-0.35; P

CONCLUSIONS: In a prospectively recruited cohort of 76 participants undergoing cardioversion for AF, we found that a novel algorithm analyzing signals recorded using an iPhone 4S accurately distinguished pulse recordings during AF from sinus rhythm. Data are needed to explore the performance and acceptability of smartphone-based applications for AF detection.

METHODS AND RESULTS: 46 participants with persistent AF and 41 age-matched participants with no AF were recruited. LAS and LASt were measured before and immediately after CV using 2D speckle tracking imaging (2DSI). Maintenance of sinus rhythm was assessed over a 6-month follow up. Mean LAS was lower, and mean LASt higher, in participants with AF before CV as compared to control group (11.9 +/- 1.0 vs 35.7 +/- 1.7, p

CONCLUSIONS: LAS and LASt differed between participants with and without AF, irrespective of the rhythm at the time of echocardiographic assessment. Baseline LAS and LASt were not associated with AF recurrence. However, change in LAS after CV may be a useful predictor of recurrent arrhythmia.

RESULTS: Score reliabilities were good (CMLT-Listening: alpha=.84) to adequate (CMLT-Reading: alpha=.75). Scores on both CMLT tests were positively and significantly correlated with scores on the REALM, numeracy, cancer knowledge and the cognitive tests. Mean CMLT scores varied as predicted according to educational level, language spoken at home, self-rated health, self-reported reading, and self-rated ability to comprehend spoken information.

CONCLUSION: The psychometric findings for both tests are promising. Scores appear to be valid indicators of comprehension of spoken and written health messages about cancer prevention and screening.

PRACTICE IMPLICATIONS: The CMLT-Listening will facilitate research into comprehension of spoken health messages, and together with the CMLT-Reading will allow researchers to examine the unique contributions of listening and reading comprehension to health-related decisions and behaviors.

METHODS: We identified patients (>/=18 years of age) cared for in the setting of a multispecialty group practice with documentation of at least one health care encounter associated with a gout diagnosis during the period 2008-2009 (n = 1346). Patients were sent a questionnaire assessing knowledge with regard to gout, beliefs about prescription medications used to treat gout, and trust in the physician. Administrative electronic health records were used to identify prescription drug use and health care utilization.

RESULTS: Two hundred and forty patients returned surveys out of the 500 contacted for participation. Most were male (80%), white (94%), and aged 65 and older (66%). Only 14 (6%) patients were treated by a rheumatologist. Only a minority of patients were aware of common foods known to trigger gout (e.g., seafood [23%], beef [22%], pork [7%], and beer [43%]). Of those receiving a urate-lowering medication, only 12% were aware of the short-term risks of worsening gout with initiation. These deficits were more common in those with active as compared to inactive gout.

CONCLUSION: Knowledge deficits about dietary triggers and chronic medications were common, but worse in those with active gout. More attention is needed on patient education on gout and self-management training.

OBJECTIVES: To test the hypotheses that in nursing home residents with dementia prescribed warfarin have less time in therapeutic range and a higher incidence of nonpreventable and preventable adverse warfarin events compared to nursing home residents without dementia after controlling for facility and patient characteristics.

METHODS: A prospective cohort embedded in a clinical trial of nursing home residents prescribed warfarin in 26 nursing homes in Connecticut was observed for up to 12 months. The primary outcome measures included adverse warfarin events (AWEs) (injuries resulting from warfarin use), potential AWEs (INR [international normalized ratio] >4.5 and management error), and AWE preventability based on physician reviews of medical record abstractions. Potential confounders included nursing home structural characteristics (eg, number of beds and for-profit status), nursing staff time, and nursing home regulatory deficiencies (pharmacy, administrative, quality of care, and all other deficiencies). Multivariable Poisson regression analysis was used to determine the independent association of dementia with potential and preventable AWEs using generalized estimating equations to account for clustering within nursing homes.

RESULTS: Residents with dementia had no difference in the number of INR monitoring tests or percentage of days in the therapeutic range, but did have an increased risk of AWEs (adjusted incidence rate ratio [IRR], 1.47; 95% confidence interval [CI], 1.20-1.82), and preventable or potential AWEs (adjusted IRR, 1.36; 95% CI, 1.06-1.76) after adjustment for patient characteristics, nursing home quality, and case mix. Greater nursing staff time was protective for preventable and potential AWEs (adjusted IRR, 0.66; 95% CI, 0.48-0.90) but not for nonpreventable AWEs.

CONCLUSION: A diagnosis of dementia was associated with increased risk of nonpreventable and preventable or potential AWEs. Greater nursing staff time was associated with lower risk of preventable AWEs. These findings have implications for quality-of-care reporting and patient safety.

Methods: Exploratory analyses were performed in a randomized controlled trial that tested whether a patient-centered counseling intervention reduced low-density lipoprotein cholesterol levels in 355 participants with peripheral arterial disease, compared with AC and usual care (UC) conditions. The patient-centered counseling intervention was designed to activate participants to ask their physician for lipid-lowering medication and/or increase dose intensity, increase medication adherence, and reduce fat intake. The AC condition involved attention-matched telephone-delivered health education, and the UC condition consisted of an educational pamphlet.

Results: At 12-month follow-up, the mean low-density lipoprotein cholesterol changes were -11.1 and -6.8 mg/dL in the UC and AC conditions, respectively (p = .17). The proportion of participants who increased the use or dose intensity of medication was significantly lower in AC than in UC: 17.5% versus 30.5% (p = .03). No significant difference in other outcomes was observed between AC and UC.

Conclusions: AC has significantly worse medication outcomes, and there is no indication of a therapeutic effect on other end points. Implications for the use of AC in behavioral randomized trials are discussed.

Trial Registration:clinicaltrials.gov Identifier: NCT00217919.

OBJECTIVE: To describe factors, including patient-reported reasons, associated with non-completion of ordered laboratory tests.

DESIGN: Mixed-Methods study including a quantitative assessment of the frequency of patient completion of ordered monitoring tests combined with qualitative, semi-structured, patient interviews.

PARTICIPANTS: Quantitative assessment included patients 18 years or older from a large multispecialty group practice, who were prescribed a medication requiring monitoring. Qualitative interviews included a subset of show and no-show patients prescribed a cardiovascular, anticonvulsant, or thyroid replacement medication.

MAIN MEASURES: Proportion of recommended monitoring tests for each medication not completed, factors associated with patient non-completion, and patient-reported reasons for non-completion.

KEY RESULTS: Of 27,802 patients who were prescribed one of 34 medications, patient non-completion of ordered tests varied (range: 0-24 %, by drug-test pair). Factors associated with higher odds of test non-completion included: younger patient age (< 40 years vs. >/= 80 years, adjusted odds ratio [AOR] 1.52, 95 % confidence interval [95 % CI] 1.27-1.83); lower medication burden (one medication vs. more than one drug, AOR for non-completion 1.26, 95 % CI 1.15-1.37), and lower visit frequency (0-5 visits/year vs. >/= 19 visits/year, AOR 1.41, 95 % CI 1.25 to 1.59). Drug-test pairs with black box warning status were associated with greater odds of non-completion, compared to drugs without a black box warning or other guideline for testing (AOR 1.91, 95 % CI 1.66-2.19). Qualitative interviews, with 16 no-show and seven show patients, identified forgetting as the main cause of non-completion of ordered tests.

CONCLUSIONS: Patient non-completion contributed to missed opportunities to monitor medications, and was associated with younger patient age, lower medication burden and black box warning status. Interventions to improve laboratory monitoring should target patients as well as physicians.

METHODS: A 1-page standardized encounter form was developed to document topics discussed during visits with diabetes patients. A portion of the form was designed to be used as a script to guide the interaction and assist patients in setting appropriate self-management goals. Data were also collected via CHW work logs and interviews with CHWs and their supervisors to validate findings.

RESULTS: Data were collected for 1198 interactions with 540 patients at 6 community health centers. Self-management goals were set during 62% of encounters. With respect to the most recent self-management goal set, patients who had set a challenging goal were more likely to be in the action stage of change than in other stages. Work logs revealed that CHWs engaged in a number of activities not involving direct patient interactions and thus not captured on encounter forms.

CONCLUSIONS: Evaluating and monitoring CHWs' daily activities has been challenging. Encounter forms have great potential for documenting the work of CHWs with patients.