Maternal Phenylketonuria: Long-term Outcomes in Offspring and Post-pregnancy Maternal Characteristics.

Maternal phenylketonuria (MPKU) is a well-recognized complication of PKU and one of the most potent teratogenic syndromes of pregnancy. Virtually all offspring from untreated pregnancies in women with classic PKU have intellectual disabilities and microcephaly. Congenital heart disease and intrauterine growth retardation occur many times more often than expected in the general population. Control of maternal blood phenylalanine during pregnancy prevents most if not all of these complications. Previous studies demonstrated the benefits of treatment in terms of birth parameters and early development. In this study, physical examinations, a medical history, and neuropsychological evaluation were obtained in 47 children from 24 mothers with PKU who received treatment during pregnancy. Mothers were interviewed and administered an abbreviated IQ test. Associations between maternal factors and offspring outcomes were also analyzed.The 21 male and 26 female offspring ranged in age from 1 month to 26 years with 21 (62%) over 6 years. Results indicated mean intercanthal distances above the 70th percentile. Microcephaly was present in 19% of offspring, with head circumference below the third percentile. None of the offspring had cardiac anomalies. Mean offspring IQ was 94 ± 19, with 12% performing in the range of intellectual disability (IQ < 70). Among children >5 years of age, 25% had learning disabilities, 31% had attention deficit hyperactivity disorder (ADHD), 22% were on ADHD medication, and 34% had a diagnosis of anxiety and/or depression. Among the 24 mothers, 12 reported following the diet for PKU. Only one woman on diet had a blood phenylalanine concentration <360 µmol/L (recommended range) and the majority had indications of poor nutritional status. Mean maternal Full Scale IQ was 94 ± 16 (range = 61-117), with 25% performing in the borderline intellectual range (IQ < 85). Verbal IQ was significantly lower than Performance IQ (p = 0.01, CI 2.7, 16.1). On the self-report Beck Depression Inventory, Second Edition, 25% received scores indicating mild to moderate depression, and on the Beck Anxiety Inventory, 46% reported mild to moderate anxiety. Offspring IQ correlated with maternal metabolic control during pregnancy (r = 0.51), maternal IQ (r = -0.62), and socioeconomic position (r = -0.48). Offspring with ADHD, learning disabilities, or emotional disturbances were more likely to have mothers with anxiety and/or depression. To ensure optimal offspring outcomes, healthcare providers need to assess maternal nutrition, blood phenylalanine concentrations, cognitive abilities, and socioeconomic position. Interventions can then be initiated that reduce psychosocial stressors and enhance adherence to diet and positive parenting, which in turn can lead to better cognitive functioning, behavior, and emotional well-being in their children.

Pathways to poor anticoagulation control.

BACKGROUND: While a considerable amount is known about which patient-level factors predict poor anticoagulation control with warfarin, measured by percent time in therapeutic range (TTR), less is known about predictors of time above or below target. OBJECTIVE: To identify predictors of different patterns of international normalized ratio (INR) values that account for poor control, including 'erratic' patterns, where more time is spent both above and below INR target, and unidirectional patterns, where time out of range is predominantly in one direction (low or high). METHODS: We studied 103 897 patients receiving warfarin with a target INR of 2-3 from 100 Veterans Health Administration sites between October 2006 and September 2008. Our outcomes were percent time above and below the target range. Predictors included patients' demographics, comorbidities, and other clinical data. RESULTS: Predictors of erratic patterns included alcohol abuse (5.2% more time below and 3.7% more time above, P < 0.001 for all results), taking > 16 medications (4.6% more time below and 1.8% more time above compared to taking seven or fewer medications), and four or more hospitalizations during the study (6.6% more time below and 2% more time above compared to no hospitalization). In contrast, predictors like cancer, non-alcohol drug abuse, dementia, and bipolar disorder were associated with more time below the target range (3.4%, 5.2%, 2.6%, and 3.2%, respectively) and less (or similar) time above range. CONCLUSION: Different patient-level factors predicted unidirectional below-target and 'erratic' patterns of INR control. Distinct interventions are necessary to address these two separate pathways to poor anticoagulation.

Clinical significance of trochlear calcifications in the orbit.

BACKGROUND AND PURPOSE: Trochlear calcification is frequently seen on CT scans that include the orbits, but prior studies linking this finding to diabetes mellitus were based on selected populations by using relatively thick sections. We assessed the relationship between trochlear calcification and diabetes mellitus and other chronic medical conditions in an unrestricted population by using thin-section CT. MATERIALS AND METHODS: Noncontrast head CT studies performed consecutively on 1000 patients between January and February 2011 were retrospectively reviewed for the presence of trochlear calcifications. Axial 1.25-mm-thick images acquired by 64-detector row CT were reviewed. Medical records were reviewed for chronic medical conditions, including diabetes mellitus, chronic kidney disease, alcoholism, autoimmune conditions, endocrine disorders, serum calcium and alkaline phosphatase levels, and HIV status. Motion-limited studies and patients with limited clinical data were excluded. Statistical analyses were performed by using the Fisher exact test. RESULTS: Thirty-two patients were excluded from analysis. Of the remaining 968 patients, 128 had trochlear calcification (13%). No significant association was observed between diabetes mellitus and trochlear calcifications in patients of any age (P = .40). There was no significant correlation between trochlear calcifications and chronic kidney disease, alcoholism, endocrine disorders, or HIV infection. Statistically significant associations among trochlear calcification, autoimmune conditions, and elevated alkaline phosphatase levels were observed (P < .0001 and P < .0001, respectively). CONCLUSIONS: On the basis of a large unrestricted population with thin-section CT imaging of the orbit, no significant association was observed between trochlear calcifications and diabetes mellitus. A statistically significant association was observed between trochlear calcification and autoimmune disease and elevated alkaline phosphatase levels.

Quantitative MRI analysis of craniofacial bone marrow in patients with sickle cell disease.

BACKGROUND AND PURPOSE: Assessment of bone marrow is most commonly performed qualitatively in the spine or other large long bones. The craniofacial bones are less ideal for bone marrow analysis because of the relatively small bone marrow volume. Because patients with SCD often undergo repeated brain imaging to evaluate for cerebral vaso-occlusive disease, quantitative assessment of craniofacial bone marrow is a reasonable possibility in these patients. The purpose of this study was to investigate specific sickle cell disease changes in craniofacial bone marrow quantitatively by analyzing T1, T2, and secular-T2 relaxation times and volume with the use of quantitative MRI. MATERIALS AND METHODS: Fourteen patients with SCD and 17 control subjects were imaged with the mixed TSE pulse sequence at 1.5T. The craniofacial bones were manually segmented by using 3D Slicer to generate bone marrow volumes and to provide T1, T2, and secular-T2 relaxation times. RESULTS: All subjects exhibited a bimodal T1 histogram. In the SCD group, there was a decrease in amplitude in the first T1 peak and an increase in amplitude in the second T1 peak. The first T1 peak showed a significant increase in relaxation time compared with control subjects (P < .0001), whereas there was no significant difference in the second T1 peak. T2 and secular-T2 relaxation times were significantly shorter in the SCD group (T2, P < .0001; secular-T2, P < .0001). Increasing numbers of blood transfusions resulted in a decrease in T2 and secular-T2 times. Patients with SCD exhibited a larger bone marrow volume compared with control subjects, even after standardization. CONCLUSIONS: Patients with SCD exhibited significant quantifiable changes in the craniofacial bone marrow because of failure of red-to-yellow marrow conversion and iron deposition that can be identified by qMRI relaxometry and volumetry. Both qMRI relaxometry and volumetry may be used as noninvasive tools for assessment of disease severity.

Quantitative MRI analysis of salivary glands in sickle cell disease.

OBJECTIVES: The purpose of this prospective study was to characterize the MR relaxometric features of the major salivary glands in patients with sickle cell disease (SCD). METHODS: 15 patients with SCD (aged 19.8-43.6 years) and 12 controls were imaged with the mixed turbo-spin echo pulse sequence. The major salivary glands were manually segmented and T1, T2 and secular T2 relaxometry histograms were modelled with Gaussian functions. RESULTS: Shortened T1 relaxation times were seen solely in the submandibular glands of patients with SCD (747.5±54.8 ms vs 807.1±38.3 ms, p<0.001). Slight T2 and secular T2 shortening were seen in the parotid gland; however, this difference was not significant (p=0.07). The sublingual gland showed no changes under MR relaxometry. There was no difference in glandular volumes, and no correlation was demonstrated between history of blood transfusion and salivary gland relaxometry. CONCLUSIONS: Patients with SCD exhibited changes in quantitative MRI T1 relaxometry histograms of the submandibular glands.

Explanatory factors of sexual function in sexual minority women breast cancer survivors.

BACKGROUND: The sexual function of sexual minority women (women with female partners) who are breast cancer survivors is mostly unknown. Our objective is to identify explanatory factors of sexual function among sexual minority women with breast cancer and compare them with a control sample of sexual minority women without cancer. PATIENTS AND METHODS: Using a conceptual framework that has previously been applied to heterosexual breast cancer survivors, we assessed the relationship of each explanatory factor to sexual function in sexual minority women. Using generalized estimating equations, we identified explanatory factors of sexual function and identified differences by case and control status. RESULTS: Self-perception of greater sexual attractiveness and worse urogenital menopausal symptoms explain 44% of sexual function, after controlling for case and control status. Focusing only on partnered women, 45% of sexual function was explained by greater sexual attractiveness, postmenopausal status, and greater dyadic cohesion. CONCLUSIONS: All of the relevant explanatory factors for sexual function among sexual minority survivors are modifiable as has been suggested for heterosexual survivors. Sexual minority survivors differ from heterosexual survivors in that health-related quality of life is less important as an explanatory factor. These findings can guide adaptation of interventions for sexual minority survivors.

An ecological approach to examine lung cancer disparities due to sexual orientation.

OBJECTIVES: To determine whether there is an association between geographical areas with greater sexual minority density, defined as gay and lesbian individuals, and incidence and mortality rates for lung cancer. STUDY DESIGN: As individual surveillance data on sexual orientation are not available, this study used an ecological approach to examine the link between sexual minorities and lung cancer. METHODS: Population-based surveillance data on the incidence of and mortality due to lung cancer from 1996 to 2004 were used from 12 Surveillance, Epidemiology and End Results (SEER) registries and 2000 Census data on same-sex-partnered households for the geographical area covered by SEER 12. Using multiple regression models, the county-level association of sexual minority density with incidence or mortality rates for lung cancer was examined. RESULTS: A significant positive association was found between both incidence and mortality rates for lung cancer and areas with a higher density of sexual minority men, and a significant negative association was found between both incidence and mortality rates for lung cancer and areas with a higher density of sexual minority women. CONCLUSIONS: In the absence of surveillance data, this novel methodological strategy approximates population-level lung cancer disparities for sexual minority populations at the aggregate level.

INR targets and site-level anticoagulation control: results from the Veterans AffaiRs Study to Improve Anticoagulation (VARIA).

BACKGROUND: Not all clinicians target the same International Normalized Ratio (INR) for patients with a guideline-recommended target range of 2-3. A patient's mean INR value suggests the INR that was actually targeted. We hypothesized that sites would vary by mean INR, and that sites of care with mean values nearest to 2.5 would achieve better anticoagulation control, as measured by per cent time in therapeutic range (TTR). OBJECTIVES: To examine variations among sites in mean INR and the relationship with anticoagulation control in an integrated system of care. PATIENTS/METHODS: We studied 103,897 patients receiving oral anticoagulation with an expected INR target between 2 and 3 at 100 Veterans Health Administration (VA) sites from 1 October 2006 to 30 September 2008. Key site-level variables were: proportion near 2.5 (that is, percentage of patients with mean INR between 2.3 and 2.7) and mean risk-adjusted TTR. RESULTS: Site mean INR ranged from 2.22 to 2.89; proportion near 2.5, from 30 to 64%. Sites' proportions of patients near 2.5, below 2.3 and above 2.7 were consistent from year to year. A 10 percentage point increase in the proportion near 2.5 predicted a 3.8 percentage point increase in risk-adjusted TTR (P < 0.001). CONCLUSIONS: Proportion of patients with mean INR near 2.5 is a site-level 'signature' of care and an implicit measure of targeted INR. This proportion varies by site and is strongly associated with site-level TTR. Our study suggests that sites wishing to improve TTR, and thereby improve patient outcomes, should avoid the explicit or implicit pursuit of non-standard INR targets.

Urinary biomarkers of occupational jet fuel exposure among Air Force personnel.

There is a potential for widespread occupational exposure to jet fuel among military and civilian personnel. Urinary metabolites of naphthalene have been suggested for use as short-term biomarkers of exposure to jet fuel (jet propulsion fuel 8 (JP8)). In this study, urinary biomarkers of JP8 were evaluated among US Air Force personnel. Personnel (n=24) were divided a priori into high, moderate, and low exposure groups. Pre- and post-shift urine samples were collected from each worker over three workdays and analyzed for metabolites of naphthalene (1- and 2-naphthol). Questionnaires and breathing-zone naphthalene samples were collected from each worker during the same workdays. Linear mixed-effects models were used to evaluate the exposure data. Post-shift levels of 1- and 2-naphthol varied significantly by a priori exposure group (levels in high group>moderate group>low group), and breathing-zone naphthalene was a significant predictor of post-shift levels of 1- and 2-naphthol, indicating that for every unit increase in breathing-zone naphthalene, there was an increase in naphthol levels. These results indicate that post-shift levels of urinary 1- and 2-naphthol reflect JP8 exposure during the work-shift and may be useful surrogates of JP8 exposure. Among the high exposed workers, significant job-related predictors of post-shift levels of 1- and 2-naphthol included entering the fuel tank, repairing leaks, direct skin contact with JP8, and not wearing gloves during the work-shift. The job-related predictors of 1- and 2-naphthol emphasize the importance of reducing inhalation and dermal exposure through the use of personal protective equipment while working in an environment with JP8.

Prediction of locoregional control in head and neck squamous cell carcinoma with serial CT perfusion during radiotherapy.

BACKGROUND AND PURPOSE: Tumor hypoxia is a known factor of radioresistance in HNSCC. CTP is a noninvasive method of measuring tumor perfusion in vivo. The purpose of our study was to determine serial changes in tumor perfusion in HNSCC during a course of RT by using CTP and to correlate tumor perfusion measurements to LRC. MATERIALS AND METHODS: A prospective study was performed in 15 patients with HNSCC receiving definitive RT who underwent serial CTP before RT; at weeks 2, 4, and 6 of RT; and 6 weeks after RT. The median follow-up was 28 months (range, 6-44 months). Thirteen patients achieved LRC, and 2 patients had LRF. Tumor perfusion parameters, including BF, BV, MTT, and CP, were obtained by using a deconvolution-based analysis. RESULTS: Pretreatment tumor BF was significantly higher in patients who achieved LRC, 118.0 mL/100 g/min, compared with those with LRF, 53.4 mL/100 g/min (P = .004). Similarly, pretreatment CP was higher in patients with LRC, 16.6 mL/100 g/min, compared with those with LRF, 7.7 mL/100 g/min (P = .02). At week 2 of RT, tumor BF parameters showed a 27.5% increase versus an 18.1% decrease from pretreatment BF values (P = .046) in patients with LRC and LRF, respectively. A decrease in BF and BV was observed in both groups 6 weeks after RT compared with these values at baseline scanning. CONCLUSIONS: An increase in tumor BF and CP by using CTP early during a course of RT predicts LRC in patients with HNSCC treated with RT.

Superior semicircular canal dehiscence: congenital or acquired condition?

BACKGROUND AND PURPOSE: It remains unclear whether SSCD syndrome, characterized by onset of vestibular symptoms in the setting of loud noises, is a congenital or acquired condition. The purpose of this investigation was to assess the prevalence of SSCD on imaging among multiple age groups to determine whether this condition is more likely to be congenital or acquired. MATERIALS AND METHODS: Following approval of the institutional review board, 306 consecutive temporal bone CT examinations performed between July 2005 and March 2007 were retrospectively reviewed. Of these, 2 patients were eliminated due to destructive processes in the inner ear. Patients ranged in age from 7 months to 89 years. Images were independently evaluated by 2 neuroradiologists, and the superior semicircular canal was characterized as normal, thin, or frankly dehiscent in each temporal bone. Any discrepancies were resolved by consensus. The patient list was then subcategorized into 5 age groups, and the prevalence of SSCD was calculated for each group. RESULTS: Twenty-four patients were identified with SSCD, of which 6 demonstrated dehiscence bilaterally. One hundred thirty-seven subjects were identified with thinning, of which 50 demonstrated thinning bilaterally. Each successively older age category experienced a 93% increase (95% CI, 30%-187%) in the prevalence of SSCD (P = .001) and a 9% increase (95% CI, -5%-25%) in the prevalence of thinning (P = .21). Neither crude nor age-adjusted models demonstrated a significant association between thinning and contralateral dehiscence or vice versa. CONCLUSIONS: The increased radiologic prevalence of SSCD among older age groups suggests that this is more commonly an acquired rather than congenital condition.

Patient characteristics associated with oral anticoagulation control: results of the Veterans AffaiRs Study to Improve Anticoagulation (VARIA).

BACKGROUND: In patients receiving oral anticoagulation, improved control can reduce adverse outcomes such as stroke and major hemorrhage. However, little is known about patient-level predictors of anticoagulation control. OBJECTIVES: To identify patient-level predictors of oral anticoagulation control in the outpatient setting. PATIENTS/METHODS: We studied 124,619 patients who received oral anticoagulation from the Veterans Health Administration from October 2006 to September 2008. The outcome was anticoagulation control, summarized using percentage of time in therapeutic International Normalized Ratio range (TTR). Data were divided into inception (first 6 months of therapy; 39,447 patients) and experienced (any time thereafter; 104,505 patients). Patient-level predictors of TTR were examined by multivariable regression. RESULTS: Mean TTRs were 48% for inception management and 61% for experienced management. During inception, important predictors of TTR included hospitalizations (the expected TTR was 7.3% lower for those with two or more hospitalizations than for the non-hospitalized), receipt of more medications (16 or more medications predicted a 4.3% lower than for patients with 0-7 medications), alcohol abuse (-4.6%), cancer (-3.1%), and bipolar disorder (-2.9%). During the experienced period, important predictors of TTR included hospitalizations (four or more hospitalizations predicted 9.4% lower TTR), more medications (16 or more medications predicted 5.1% lower TTR), alcohol abuse (-5.4%), female sex (- 2.9%), cancer (-2.7%), dementia (-2.6%), non-alcohol substance abuse (-2.4%), and chronic liver disease (-2.3%). CONCLUSIONS: Some patients receiving oral anticoagulation therapy are more challenging to maintain within the therapeutic range than others. Our findings can be used to identify patients who require closer attention or innovative management strategies to maximize benefit and minimize harm from oral anticoagulation therapy.

Volumetric and semiquantitative assessment of MRI-detected subchondral bone marrow lesions in knee osteoarthritis: a comparison of contrast-enhanced and non-enhanced imaging.

OBJECTIVE: Aim was to compare volumetric and semi-quantitative (SQ) measurements of subchondral bone marrow lesions (BMLs) on non-fat-suppressed (FS) T1-weighted (w), T1-w FS contrast enhanced (CE) and proton density (PD)-w FS images in order to define which sequence depicts the lesions to their maximum extent and if T1-w FS CE images and PD-w FS images may be used interchangeably to assess BMLs in a volumetric or SQ fashion. DESIGN: Thirty-two patients with clinical knee osteoarthritis (OA) were scanned on a standard 1.5 T MRI system. A total of 47 BMLs were identified and were manually segmented on all three sequences. BMLs were also assessed semiquantitatively using the Whole Organ Magnetic Resonance Imaging Score (WORMS). The volumetric and SQ results were compared across the three imaging sequences using paired t-tests. RESULTS: Eighty-three percent of the lesions appeared largest on the PD-w FS sequence. Significant differences were observed for volumetric measurements between all three sequences (P < 0.001), however the mean volume difference between PD-w FS and T1-w FS CE (38%) was much smaller than for non-FS T1-w and PD-w FS/T1-w FS CE sequences (195% and 114%, respectively). Significant differences in WORMS scores were noted between PD-w FS and non-FS T1-w images and between T1-w FS CE and non-FS T1-w images (P < 0.001), but no significant difference was observed between PD-w FS and T1-w FS CE images. CONCLUSION: Our findings suggest that the T1-w FS CE and PD-w FS sequences may be interchangeably used for quantitative volumetric and SQ assessment of BMLs.

Anticoagulation for valvular heart disease in community-based practice.

Little is known about patients who receive oral anticoagulation for valvular heart disease (VHD) in community-based practice. It was this study's objective to describe the characteristics, management, and outcomes of patients anticoagulated for VHD, compared to patients anticoagulated for atrial fibrillation (AF). We used a nationally-representative cohort of community-based anticoagulation care in the United States. Data collected included indications for therapy, demographics, selected comorbid conditions, international normalised ratio (INR) target ranges, INR control, and clinical outcomes. We identified 1,057 patients anticoagulated for VHD (15.6% of the overall cohort) and 3,396 patients anticoagulated for AF (50.2%). INR variability was similar between the two groups (0.64 vs. 0.69, p = 0.80). Among patients with aortic VHD, for whom a standard (2-3) target INR range is recommended, 461 (84%) had a high target range (2.5-3.5), while 95 (16%) had a standard target range. VHD patients had a higher rate of major haemorrhage compared to AF patients (3.57 vs. 1.78 events per 100 patient-years, incidence rate ratio 2.02, 95% CI 1.33 - 3.06). The rate of stroke/systemic embolus was similar between groups (0.67 vs. 0.97 events per 100 patient-years, incidence rate ratio 0.71, 95% CI 0.32 - 1.57). In our community-based study, approximately 15.6% of patients receiving warfarin were anticoagulated for VHD. VHD patients achieved similar anticoagulation control to patients with AF, as measured by INR variability. Nevertheless, the rate of major haemorrhage was elevated among VHD patients compared to AF patients; this finding requires further investigation.

Power to detect spatial disturbances under different levels of geographic aggregation.

OBJECTIVE: Spatio and/or temporal surveillance systems are designed to monitor the ongoing appearance of disease cases in space and time, and to detect potential disturbances in either dimension. Patient addresses are sometimes reported at some level of geographic aggregation, for example by ZIP code or census tract. While this aggregation has the advantage of protecting patient privacy, it also risks compromising statistical efficiency. This paper investigated the variation in power to detect a change in the spatial distribution in the presence of spatial aggregation. METHODS: The authors generated 400,000 spatial datasets with varying location and spread of simulated spatial disturbances, both on a purely synthetic uniform population, and on a heterogeneous population, representing hospital admissions to three community hospitals in Cape Cod, Massachusetts. The authors evaluated the power of the M-statistic to detect spatial disturbances, comparing the use of exact spatial locations versus twelve different levels of aggregation, where the M-statistic is a comparison of two distributions of interpoint distances between locations. RESULTS: When the spread of simulated spatial disturbances was contained to a small portion of the study region or affects a large proportion of the population at risk, power was highest when exact locations were reported. If the spatial disturbance was a more modest signal, the best power was attained at an aggregated level. CONCLUSIONS: The precision at which patients' locations are reported has the potential to affect the power of detection significantly.

Warfarin dose management affects INR control.

BACKGROUND: Little is known about how patterns of warfarin dose management contribute to percentage time in the therapeutic International Normalized Ratio (INR) range (TTR). OBJECTIVES: To quantify the contribution of warfarin dose management to TTR and to define an optimal dose management strategy. PATIENTS/METHODS: We enrolled 3961 patients receiving warfarin from 94 community-based clinics. We derived and validated a model for the probability of a warfarin dose change under various conditions. For each patient, we computed an observed minus expected (O - E) score, comparing the number of dose changes predicted by our model to the number of changes observed. We examined the ability of O - E scores to predict TTR, and simulated various dose management strategies in the context of our model. RESULTS: Patients were observed for a mean of 15.2 months. Patients who deviated the least from the predicted number of dose changes achieved the best INR control (mean TTR 70.1% unadjusted); patients with greater deviations had lower TTR (65.8% and 62.0% for fewer and more dose changes respectively, Bonferroni-adjusted P < 0.05/3 for both comparisons). On average, clinicians in our study changed the dose when the INR was 1.8 or lower/3.2 or higher (mean TTR: 68%); optimal management would have been to change the dose when the INR was 1.7 or lower/3.3 or higher (predicted TTR: 74%). CONCLUSIONS: Our observational study suggests that INR control could be improved considerably by changing the warfarin dose only when the INR is 1.7 or lower/3.3 or higher. This should be confirmed in a randomized trial.

Warfarin for atrial fibrillation in community-based practise.

BACKGROUND: Previous studies of anticoagulation for atrial fibrillation (AF) have predominantly occurred in academic settings or randomized trials, limiting their generalizability. OBJECTIVE: To describe the management of patients with AF anticoagulated with warfarin in community-based practise. METHODS: We enrolled 3396 patients from 101 community-based practises in 38 states. Data included demographics, comorbidities, and International Normalized Ratio (INR) values. Outcomes included time in therapeutic INR range (TTR), stroke, and major hemorrhage. RESULTS: The mean TTR was 66.5%, but varied widely among patients: 37% had TTR above 75%, while 34% had TTR below 60%. The yearly rates of major hemorrhage and stroke were 1.90 per 100 person-years and 1.00 per 100 person-years. Four percent of patients (n = 127) were intentionally targeted to a lower INR, and spent 42.7% of time with an INR below 2.0, compared to 18.8% for patients with a 2.0-3.0 range (P < 0.001). Mean TTR for new warfarin users (57.5%) remained below that of prevalent users through the first six months. Patients with interruptions of warfarin therapy had lower TTR than all others (61.6% vs. 67.2%, P < 0.001), which corrected after deleting low peri-procedural INR values (67.0% vs. 67.4%, P = 0.73). CONCLUSIONS: Anticoagulation control varies widely among patients taking warfarin for AF. TTR is affected by new warfarin use, procedural interruptions, and INR target range. In this community-based cohort of predominantly prevalent warfarin users, rates of hemorrhage and stroke were low. The risk versus benefit of a lower INR target range to offset bleeding risk remains uncertain.