Al Ozonoff

Opioid overdose rates and implementation of overdose education and nasal naloxone distribution in Massachusetts: interrupted time series analysis

Objective To evaluate the impact of state supported overdose education and nasal naloxone distribution (OEND) programs on rates of opioid related death from overdose and acute care utilization in Massachusetts. Design Interrupted time series analysis of opioid related overdose death and acute care utilization rates from 2002 to 2009 comparing community-year strata with high and low rates of OEND implementation to those with no implementation. Setting 19 Massachusetts communities (geographically distinct cities and towns) with at least five fatal opioid overdoses in each of the years 2004 to 2006. Participants OEND was implemented among opioid users at risk for overdose, social service agency staff, family, and friends of opioid users. Intervention OEND programs equipped people at risk for overdose and bystanders with nasal naloxone rescue kits and trained them how to prevent, recognize, and respond to an overdose by engaging emergency medical services, providing rescue breathing, and delivering naloxone. Main outcome measures Adjusted rate ratios for annual deaths related to opioid overdose and utilization of acute care hospitals. Results Among these communities, OEND programs trained 2912 potential bystanders who reported 327 rescues. Both community-year strata with 1-100 enrollments per 100 000 population (adjusted rate ratio 0.73, 95% confidence interval 0.57 to 0.91) and community-year strata with greater than 100 enrollments per 100 000 population (0.54, 0.39 to 0.76) had significantly reduced adjusted rate ratios compared with communities with no implementation. Differences in rates of acute care hospital utilization were not significant. Conclusions Opioid overdose death rates were reduced in communities where OEND was implemented. This study provides observational evidence that by training potential bystanders to prevent, recognize, and respond to opioid overdoses, OEND is an effective intervention.

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

Summary.  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.

Risk-Adjusted Percent Time in Therapeutic Range as a Quality Indicator for Outpatient Oral Anticoagulation Results of the Veterans Affairs Study To Improve Anticoagulation (VARIA)

Background— Oral anticoagulation is safer and more effective when patients receive high-quality care. However, there have been no prior efforts to measure quality of oral anticoagulation care or to risk adjust it to ensure credible comparisons. Our objective was to profile site performance in the Veterans Health Administration (VA) using risk-adjusted percent time in therapeutic range (TTR). Methods and Results— We included 124 551 patients who received outpatient oral anticoagulation from 100 VA sites of care for indications other than valvular heart disease from October 1, 2006, to September 30, 2008. We calculated TTR for each patient and mean TTR for each site of care. Expected TTR was calculated for each patient and each site based on the variables in the risk adjustment model, which included demographics, comorbid conditions, medications, and hospitalizations. Mean TTR for the entire sample was 58%. Site-observed TTR varied from 38% to 69% or from poor to excellent. Site-expected TTR varied from 54% to 62%. Site risk-adjusted performance ranged from 18% below expected to 12% above expected. Risk adjustment did not alter performance rankings for many sites, but for other sites, it made an important difference. For example, the site ranked 27th of 100 before risk adjustment was one of the best (risk-adjusted rank, 7). Risk-adjusted site rankings were consistent from year to year (correlation between years, 0.89). Conclusions— Risk-adjusted TTR can be used to profile the quality of outpatient oral anticoagulation in a large, integrated health system. This measure can serve as the basis for quality measurement and quality improvement efforts.

Characterization of activities of daily living in individuals with mild cognitive impairment.

OBJECTIVE To determine whether participants with mild cognitive impairment (MCI) differ from cognitively normal (NC) older adults on traditional and novel informant-based measures of activities of daily living (ADL) and to identify cognitive correlates of ADLs among participants with MCI. DESIGN Cross-sectional. SETTING University medical setting. PARTICIPANTS Seventy-seven participants (NC: N = 39; MCI: N = 38), 60 to 90 years old (73.5 +/- 6.6 years; 53% female). MEASUREMENTS Neuropsychological and ADL measures. METHODS Neuropsychological tests were administered to NC and MCI participants. Informants completed the Lawton and Brody Instrumental Activities of Daily Living and Physical Self-Maintenance Scale, including instrumental (IADL) and basic ADL (BADL) scales, as well as the Functional Capacities for Activities of Daily Living (FC-ADL), an error-based ADL measure. RESULTS No statistically or clinically significant between-group differences emerged for the BADL or IADL subscales. However, a robust difference was noted for the FC-ADL scale (MCI errors > NC errors; F((1,75))= 13.6, p <0.001; d = 0.84). Among MCI participants, correlations revealed that a measure of verbal learning was the only neuropsychological correlate of FC-ADL total score (r = -0.39, df = 36, p = 0.007). No neuropsychological measures were significantly associated with the IADL or BADL subscale score. CONCLUSION Traditional measures assessing global ADLs may not be sensitive to early functional changes related to MCI; however, error-based measures may capture the subtle evolving functional decline associated with MCI. Among MCI participants, early functional difficulties are associated with verbal learning performance, possibly secondary to the hallmark cognitive impairment associated with this cohort.

Diagnostic and Prognostic Utility of Cardiovascular Magnetic Resonance Imaging in Light-Chain Cardiac Amyloidosis

Although the presence of abnormal late gadolinium enhancement (LGE) in cardiac amyloidosis has been well established, its prognostic implication and utility to identify cardiac involvement in patients with systemic amyloidosis is unknown. The aim of this study was to assess the diagnostic and prognostic significance of cardiovascular magnetic resonance imaging in patients with amyloid light-chain amyloidosis but unknown cardiac involvement. Cardiovascular magnetic resonance imaging with LGE was performed in 28 patients with systemic amyloidosis. The presence of cardiac amyloidosis was determined by separate clinical evaluation. The performance of LGE for the prediction of cardiac amyloidosis and prognostic implications of LGE were determined. LGE was observed in 19 patients (68%). The sensitivity, specificity, positive predictive value, and negative predictive value of LGE for the identification of clinical cardiac involvement were 86%, 86%, 95%, and 67%, respectively. During a median follow-up period of 29 months, there were 5 deaths (82% survival). LGE itself did not predict survival (p = 0.62). LGE volume was positively correlated with serum level of B-type natriuretic peptide (BNP; R = 0.64, p < or =0.001), and in multivariate analysis, LGE volume proved the strongest independent predictor of BNP. BNP was correlated with New York Heart Association class (p = 0.03). Reduced right ventricular end-diastolic volume (p <0.01) and stroke volume (p = 0.02) were associated with mortality. In conclusion, in patients with systemic amyloidosis, LGE is highly sensitive and specific for the identification of cardiac involvement but does not predict survival. LGE is strongly correlated with heart failure severity as assessed by BNP.

Breast Cancer: Comparative Effectiveness of Positron Emission Mammography and MR Imaging in Presurgical Planning for the Ipsilateral Breast

PURPOSE To determine the performance of positron emission mammography (PEM), as compared with magnetic resonance (MR) imaging, including the effect on surgical management, in ipsilateral breasts with cancer. MATERIALS AND METHODS Four hundred seventy-two women with newly diagnosed breast cancer who were offered breast-conserving surgery consented from September 2006 to November 2008 to participate in a multicenter institutional review board-approved, HIPAA-compliant protocol. Participants underwent contrast material-enhanced MR imaging and fluorine 18 fluorodeoxyglucose PEM in randomized order; resultant images were interpreted independently. Added biopsies and changes in surgical procedure for the ipsilateral breast were correlated with histopathologic findings. Performance characteristics were compared by using the McNemar test and generalized estimating equations. RESULTS Three hundred eighty-eight women (median age, 58 years; age range, 26-93 years; median estimated tumor size, 1.5 cm) completed the study. Additional cancers were found in 82 (21%) women (82 ipsilateral breasts; median tumor size, 0.7 cm). Twenty-eight (34%) of the 82 breasts were identified with both PEM and MR imaging; 21 (26%) breasts, with MR imaging only; 14 (17%) breasts, with PEM only; and seven (8.5%) breasts, with mammography and ultrasonography. Twelve (15%) cases of additional cancer were missed at all imaging examinations. Integration of PEM and MR imaging increased cancer detection-to 61 (74%) of 82 breasts versus 49 (60%) of 82 breasts identified with MR imaging alone (P < .001). Of 306 breasts without additional cancer, 279 (91.2%) were correctly assessed with PEM compared with 264 (86.3%) that were correctly assessed with MR imaging (P = .03). The positive predictive value of biopsy prompted by PEM findings (47 [66%] of 71 cases) was higher than that of biopsy prompted by MR findings (61 [53%] of 116 cases) (P = .016). Of 116 additional cancers, 61 (53%) were depicted by MR imaging and 47 (41%) were depicted by PEM (P = .043). Fifty-six (14%) of the 388 women required mastectomy: 40 (71%) of these women were identified with MR imaging, and 20 (36%) were identified with PEM (P < .001). Eleven (2.8%) women underwent unnecessary mastectomy, which was prompted by only MR findings in five women, by only PEM findings in one, and by PEM and MR findings in five. Thirty-three (8.5%) women required wider excision: 24 (73%) of these women were identified with MR imaging, and 22 (67%) were identified with PEM. CONCLUSION PEM and MR imaging had comparable breast-level sensitivity, although MR imaging had greater lesion-level sensitivity and more accurately depicted the need for mastectomy. PEM had greater specificity at the breast and lesion levels. Eighty-nine (23%) participants required more extensive surgery: 61 (69%) of these women were identified with MR imaging, and 41 (46%) were identified with PEM (P = .003). Fourteen (3.6%) women had tumors seen only at PEM.

Warfarin for atrial fibrillation in community-based practise

Summary.  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.

The IL12B Gene Is Associated with Asthma

The IL12B gene on chromosome 5q31-33 encodes the p40 subunit of interleukin 12, an immunomodulatory cytokine. To test the hypothesis that the IL12B gene contains polymorphisms associated with asthma, we genotyped six haplotype-tagging polymorphisms in the IL12B gene, both in 708 children enrolled in the Childhood Asthma Management Program (CAMP) and in their parents. Using the family-based association test (FBAT) program and its haplotype (HBAT) and phenotype (PBAT) options, we tested each polymorphism and haplotype for association with asthma and asthma-related phenotypes. We tested positive associations for replication in a case-control study comparing 177 adult moderate-to-severe asthmatics with 177 nonasthmatic controls. In whites in the CAMP cohort, the A allele of the IL12B G4237A polymorphism was undertransmitted to asthmatic children (P=.0008, recessive model), the global test for haplotypes for affection status was positive (P=.009, multiallelic chi (2)), and two polymorphisms were associated with different atopy phenotypes. In addition, we found a strong association between the IL12B_4237 and IL12B_6402 polymorphisms and an asthma-severity phenotype in whites, which we also found in the independent population of white adult asthmatics. IL12B may be an important asthma gene.

Effect of an American Heart Association Get With the Guidelines program-based clinical pathway on referral and enrollment into cardiac rehabilitation after acute myocardial infarction.

Cardiac rehabilitation (CR)/secondary prevention programs are an important part of patient care after acute myocardial infarction (AMI). However, only 10% to 15% of eligible patients enroll in such programs. The purpose of this study was to evaluate the effect of an American Heart Association Get With the Guidelines (GWTG)-based clinical pathway on referral and enrollment into CR after AMI. Patients (n = 780) admitted to a single center during an 18-month period with AMI and discharged to home were evaluated retrospectively for referral and enrollment into CR programs. A total of 714 patients (92%) were on the GWTG pathway; 392 (55%) were referred and 135 (19%) were enrolled into CR. Higher referral was associated with pathway use (odds ratio [OR] 2.3, 95% confidence interval [CI] 1.1 to 4.9, p = 0.03), percutaneous coronary intervention (OR 3.1, 95% CI 1.9 to 5.2, p <0.0001), and in-patient physical therapy consultation (OR 13, 95% CI 8.2 to 20.5, p <0.0001). Ethnicity did not affect referral, but was the only variable associated with lower enrollment. Hispanic and black patients had 92% (OR 0.08, 95% CI 0.01 to 0.55, p = 0.02) and 57% (OR 0.43, 95% CI 0.19 to 1.05, p = 0.06) lower odds to enroll compared with white patients, respectively. In conclusion, use of the American Heart Association GWTG pathway showed a significantly higher referral rate to CR after AMI than previously reported in the literature. Nonetheless, most referred patients did not enroll. Strategies to bridge the gap between referral and enrollment in CR should be incorporated into AMI clinical pathways, with special emphasis on increasing enrollment in ethnic minorities.

Abdominal 64-MDCT for suspected appendicitis: the use of oral and IV contrast material versus IV contrast material only

OBJECTIVE The objective of our study was to compare the diagnostic accuracy of IV contrast-enhanced 64-MDCT with and without the use of oral contrast material in diagnosing appendicitis in patients with abdominal pain. MATERIALS AND METHODS We conducted a randomized trial of a convenience sample of adult patients presenting to an urban academic emergency department with acute nontraumatic abdominal pain and clinical suspicion of appendicitis, diverticulitis, or small-bowel obstruction. Patients were enrolled between 8 am and 11 pm when research assistants were present. Consenting subjects were randomized into one of two groups: Group 1 subjects underwent 64-MDCT performed with oral and IV contrast media and group 2 subjects underwent 64-MDCT performed solely with IV contrast material. Three expert radiologists independently reviewed the CT examinations, evaluating for the presence of appendicitis. Each radiologist interpreted 202 examinations, ensuring that each examination was interpreted by two radiologists. Individual reader performance and a combined interpretation performance of the two readers assigned to each case were calculated. In cases of disagreement, the third reader was asked to deliver a tiebreaker interpretation to be used to calculate the combined reader performance. Final outcome was based on operative, clinical, and follow-up data. We compared radiologic diagnoses with clinical outcomes to calculate the diagnostic accuracy of CT in both groups. RESULTS Of the 303 patients enrolled, 151 patients (50%) were randomized to group 1 and the remaining 152 (50%) were randomized to group 2. The combined reader performance for the diagnosis of appendicitis in group 1 was a sensitivity of 100% (95% CI, 76.8-100%) and specificity of 97.1% (95% CI, 92.7-99.2%). The performance in group 2 was a sensitivity of 100% (73.5-100%) and specificity of 97.1% (92.9-99.2%). CONCLUSION Patients presenting with nontraumatic abdominal pain imaged using 64-MDCT with isotropic reformations had similar characteristics for the diagnosis of appendicitis when IV contrast material alone was used and when oral and IV contrast media were used.