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Shear-Activated Nanoparticle Aggregates Combined With Temporary Endovascular Bypass to Treat Large Vessel Occlusion

Thu, 06/01/2017 - 9:45am

BACKGROUND AND PURPOSE: The goal of this study is to combine temporary endovascular bypass (TEB) with a novel shear-activated nanotherapeutic (SA-NT) that releases recombinant tissue-type plasminogen activator (r-tPA) when exposed to high levels of hemodynamic stress and to determine if this approach can be used to concentrate r-tPA at occlusion sites based on high shear stresses created by stent placement. METHODS: A rabbit model of carotid vessel occlusion was used to test the hypothesis that SA-NT treatment coupled with TEB provides high recanalization rates while reducing vascular injury. We evaluated angiographic recanalization with TEB alone, intra-arterial delivery of soluble r-tPA alone, or TEB combined with 2 doses of intra-arterial infusion of either the SA-NT or soluble r-tPA. Vascular injury was compared against stent-retriever thrombectomy. RESULTS: Shear-targeted delivery of r-tPA using the SA-NT resulted in the highest rate of complete recanalization when compared with controls (P=0.0011). SA-NT (20 mg) had a higher likelihood of obtaining complete recanalization as compared with TEB alone (odds ratio 65.019, 95% confidence interval 1.77, >1000; P=0.0231), intra-arterial r-tPA alone (odds ratio 65.019, 95% confidence interval 1.77, >1000; P=0.0231), or TEB with soluble r-tPA (2 mg; odds ratio 18.78, 95% confidence interval 1.28, 275.05; P=0.0322). Histological analysis showed circumferential loss of endothelium restricted to the area where the TEB was deployed; however, there was significantly less vascular injury using a TEB as compared with stent-retriever procedure (odds ratio 12.97, 95% confidence interval 8.01, 21.02; P<0.0001). CONCLUSIONS: A novel intra-arterial, nanoparticle-based thrombolytic therapy combined with TEB achieves high rates of complete recanalization. Moreover, this approach reduces vascular trauma as compared with stent-retriever thrombectomy.

Evaluation of [(1)(1)(1)In]-labeled zinc-dipicolylamine tracers for SPECT imaging of bacterial infection

Thu, 06/01/2017 - 9:45am

PURPOSE: This study prepared three structurally related zinc-dipicolylamine (ZnDPA) tracers with [(111)In] labels and conducted biodistribution and single-photon emission computed tomography/computed tomography (SPECT/CT) imaging studies of a mouse leg infection model.

PROCEDURES: Two monovalent tracers, ZnDPA-[(111)In]DTPA and ZnDPA-[(111)In]DOTA, each with a single zinc-dipicolylamine targeting unit, and a divalent tracer, Bis(ZnDPA)-[(111)In]DTPA, with two zinc-dipicolylamine units were prepared. Organ biodistribution and SPECT and CT imaging studies were performed on living mice with a leg infection created by injection of clinically relevant Gram positive Streptococcus pyogenes. Fluorescent and luminescent Eu(3+)-labeled versions of these tracers were also prepared and used to measure relative affinity for the exterior membrane surface of bacterial cells and mimics of healthy mammalian cells.

RESULTS: All three (111)In-labeled radiotracers were prepared with a radiopurity of >90 %. The biodistribution studies showed that the two monovalent tracers were cleared from the body through the liver and kidney, with retained percentage injected dose for all organs of % at 20 h and infected leg target to non-target ratio (T/NT) ratio of ≤3.0. Clearance of the divalent tracer from the bloodstream was slower and primarily through the liver, with a retained percentage injected dose for all organs <37 % at 20 h and T/NT ratio rising to 6.2 after 20 h. The SPECT/CT imaging indicated the same large difference in tracer pharmacokinetics and higher accumulation of the divalent tracer at the site of infection.

CONCLUSIONS: All three [(111)In]-ZnDPA tracers selectively targeted the site of a clinically relevant mouse infection model that could not be discerned by visual external inspection of the living animal. The highest target selectivity, observed with a divalent tracer equipped with two zinc-dipicolylamine targeting units, compares quite favorably with the imaging selectivities previously reported for other nuclear tracers that target bacterial cell surfaces. The tracer pharmacokinetics depended heavily on tracer molecular structure suggesting that it may be possible to rapidly fine tune the structural properties for optimized in vivo imaging performance and clinical translation.

Surpass flow diverter in the treatment of intracranial aneurysms: a prospective multicenter study

Thu, 06/01/2017 - 9:45am

BACKGROUND AND PURPOSE: Incomplete occlusion and recanalization of large and wide-neck brain aneurysms treated by endovascular therapy remains a challenge. We present preliminary clinical and angiographic results of an experimentally optimized Surpass flow diverter for treatment of intracranial aneurysms in a prospective, multicenter, nonrandomized, single-arm study.

MATERIALS AND METHODS: At 24 centers, 165 patients with 190 intracranial aneurysms of the anterior and posterior circulations were enrolled. The primary efficacy end point was the percentage of intracranial aneurysms with 100% occlusion on 6-month DSA. The primary safety end point was neurologic death and any stroke through a minimum follow-up of 6 months.

RESULTS: Successful flow-diverter delivery was achieved in 161 patients with 186 aneurysms (98%); the mean number of devices used per aneurysm was 1.05. Clinical follow-up (median, 6 months) of 150 patients (93.2%), showed that the primary safety end point occurred in 18 subjects. Permanent neurologic morbidity and mortality were 6% and 2.7%, respectively. Morbidity occurred in 4% and 7.4% of patients treated for aneurysms of the anterior and posterior circulation, respectively. Neurologic death during follow-up was observed in 1.6% and 7.4% of patients with treated intracranial aneurysms of the anterior and posterior circulation, respectively. Ischemic stroke at 30 days or SAH at >7 days occurred. New or worsening cranial nerve deficit was observed in 2.7%. Follow-up angiography available in 158 (86.8%) intracranial aneurysms showed 100% occlusion in 75%.

CONCLUSIONS: Clinical outcomes of the Surpass flow diverter in the treatment of intracranial aneurysms show a safety profile that is comparable with that of stent-assisted coil embolization. Angiographic results showed a high rate of intracranial aneurysm occlusion.

Early detachment of the Solitaire stent during thrombectomy retrieval: an in vitro investigation

Thu, 06/01/2017 - 9:45am

OBJECTIVE: To elucidate the early detachment of the Solitaire stent during mechanical thrombectomy, we tested the stent in vitro under various conditions and evaluated with microscopy.

METHODS: A total of five stents were tested. Using a dynamic mechanical analysis machine, we calculated the tensile force needed for separation of the four stents from the pusher wire. Stent Nos 1 and 2 were tested without any prior manipulation. During the retraction test, no sheathing around the stent-wire junction was applied to stent No 1 whereas stent No 2 was partially covered with a sheath in accordance with instructions for use (IFU) recommendations. Stent No 3 was tested after deployment and retrieval were performed three times in an in vitro vascular replica with sheathing during retrieval. Stent No 4 was tested after one deployment and retrieval using the same replica as in stent No 3 without sheathing. In addition, forward pushing force was applied intentionally during retraction to induce excessive bending of the stent. Stent No 5 was pulled apart by both hands. After separation, stent tips and pusher wires were studied for all stents under the microscope.

RESULTS: The tensile force needed for separation was about 6 N for stent Nos 1, 2, and 3, and about 4 N for stent No 4. All of the stents showed separation at the proximal marker, not at the detachment zone.

CONCLUSIONS: Detachment of the Solitaire stent during thrombectomy can be due to separation around or inside the proximal marker. Adherence to the manufacturer's IFU of partial re-sheathing during retraction and not using the device for more than two passes might decrease the possibility of such device failure.

Nonmass enhancement on breast MRI: review of patterns with radiologic-pathologic correlation and discussion of management

Thu, 06/01/2017 - 9:45am

OBJECTIVE: The purpose of this article is to review the varied appearances and associated diagnoses of nonmass enhancement on breast MRI with radiologic-pathologic correlation.

CONCLUSION: Knowledge of the distribution and internal characteristics of these findings is helpful to determine when core needle biopsy is indicated. Correlating imaging with pathologic findings is critical in making appropriate recommendations regarding clinical management.

Pitfalls in imaging of female infertility

Thu, 06/01/2017 - 9:45am

Imaging plays a crucial role in determining which factors may be involved in female infertility.

Effect of a balloon-expandable intracranial stent vs medical therapy on risk of stroke in patients with symptomatic intracranial stenosis: the VISSIT randomized clinical trial

Thu, 06/01/2017 - 9:45am

IMPORTANCE: Intracranial stenosis is one of the most common etiologies of stroke. To our knowledge, no randomized clinical trials have compared balloon-expandable stent treatment with medical therapy in symptomatic intracranial arterial stenosis.

OBJECTIVE: To evaluate the efficacy and safety of the balloon-expandable stent plus medical therapy vs medical therapy alone in patients with symptomatic intracranial stenosis (>/=70%).

DESIGN, SETTING, AND PATIENTS: VISSIT (the Vitesse Intracranial Stent Study for Ischemic Stroke Therapy) trial is an international, multicenter, 1:1 randomized, parallel group trial that enrolled patients from 27 sites (January 2009-June 2012) with last follow-up in May 2013.

INTERVENTIONS: Patients (N = 112) were randomized to receive balloon-expandable stent plus medical therapy (stent group; n = 59) or medical therapy alone (medical group; n = 53).

MAIN OUTCOMES AND MEASURES: PRIMARY OUTCOME MEASURE: a composite of stroke in the same territory within 12 months of randomization or hard transient ischemic attack (TIA) in the same territory day 2 through month 12 postrandomization. A hard TIA was defined as a transient episode of neurological dysfunction caused by focal brain or retinal ischemia lasting at least 10 minutes but resolving within 24 hours. Primary safety measure: a composite of any stroke, death, or intracranial hemorrhage within 30 days of randomization and any hard TIA between days 2 and 30 of randomization. Disability was measured with the modified Rankin Scale and general health status with the EuroQol-5D, both through month 12.

RESULTS: Enrollment was halted by the sponsor after negative results from another trial prompted an early analysis of outcomes, which suggested futility after 112 patients of a planned sample size of 250 were enrolled. The 30-day primary safety end point occurred in more patients in the stent group (14/58; 24.1% [95% CI, 13.9%-37.2%]) vs the medical group (5/53; 9.4% [95% CI, 3.1%-20.7%]) (P = .05). Intracranial hemorrhage within 30 days occurred in more patients in the stent group (5/58; 8.6% [95% CI, 2.9%-19.0%]) vs none in the medical group (95% CI, 0%-5.5%) (P = .06). The 1-year primary outcome of stroke or hard TIA occurred in more patients in the stent group (21/58; 36.2% [95% CI, 24.0-49.9]) vs the medical group (8/53; 15.1% [95% CI, 6.7-27.6]) (P = .02). Worsening of baseline disability score (modified Rankin Scale) occurred in more patients in the stent group (14/58; 24.1% [95% CI, 13.9%-37.2%]) vs the medical group (6/53; 11.3% [95% CI, 4.3%-23.0%]) (P = .09).The EuroQol-5D showed no difference in any of the 5 dimensions between groups at 12-month follow-up.

CONCLUSIONS AND RELEVANCE: Among patients with symptomatic intracranial arterial stenosis, the use of a balloon-expandable stent compared with medical therapy resulted in an increased 12-month risk of added stroke or TIA in the same territory, and increased 30-day risk of any stroke or TIA. These findings do not support the use of a balloon-expandable stent for patients with symptomatic intracranial arterial stenosis.

TRIAL REGISTRATION: Identifier: NCT00816166.

Varying the item format improved the range of measurement in patient-reported outcome measures assessing physical function

Wed, 05/31/2017 - 11:45pm

BACKGROUND: Physical function (PF) is a core patient-reported outcome domain in clinical trials in rheumatic diseases. Frequently used PF measures have ceiling effects, leading to large sample size requirements and low sensitivity to change. In most of these instruments, the response category that indicates the highest PF level is the statement that one is able to perform a given physical activity without any limitations or difficulty. This study investigates whether using an item format with an extended response scale, allowing respondents to state that the performance of an activity is easy or very easy, increases the range of precise measurement of self-reported PF.

METHODS: Three five-item PF short forms were constructed from the Patient-Reported Outcomes Measurement Information System (PROMIS(R)) wave 1 data. All forms included the same physical activities but varied in item stem and response scale: format A ("Are you able to ..."; "without any difficulty"/"unable to do"); format B ("Does your health now limit you ..."; "not at all"/"cannot do"); format C ("How difficult is it for you to ..."; "very easy"/"impossible"). Each short-form item was answered by 2217-2835 subjects. We evaluated unidimensionality and estimated a graded response model for the 15 short-form items and remaining 119 items of the PROMIS PF bank to compare item and test information for the short forms along the PF continuum. We then used simulated data for five groups with different PF levels to illustrate differences in scoring precision between the short forms using different item formats.

RESULTS: Sufficient unidimensionality of all short-form items and the original PF item bank was supported. Compared to formats A and B, format C increased the range of reliable measurement by about 0.5 standard deviations on the positive side of the PF continuum of the sample, provided more item information, and was more useful in distinguishing known groups with above-average functioning.

CONCLUSIONS: Using an item format with an extended response scale is an efficient option to increase the measurement range of self-reported physical function without changing the content of the measure or affecting the latent construct of the instrument.

Validity and Responsiveness of the Knee Injury and Osteoarthritis Outcome Score: A Comparative Study Among Total Knee Replacement Patients

Wed, 05/31/2017 - 11:45pm

OBJECTIVE: To evaluate validity and responsiveness of the Knee Injury and Osteoarthritis Outcome Score (KOOS) in relation to other patient-reported outcome measures before and after total knee replacement (TKR).

METHODS: Pre-TKR and 6-month post-TKR data from 1,143 patients in a US joint replacement cohort were used to compare the KOOS, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and the SF-36 Health Survey (SF-36). Validity was evaluated with multiple methods, including correlations of pre-TKR scale scores and analysis of variance models that used pre-TKR data to compare the relative validity of scales in discriminating between groups differing in assistive walking device use and number of comorbid conditions. Validity was also evaluated by using post-TKR minus pre-TKR change scores to assess relative validity of scales in discriminating between groups rating themselves as better, same, or worse (BSW) in their capability to do activities at 6 months. Responsiveness also was described using effect sizes and standardized response means.

RESULTS: In support of convergent and discriminant validity, KOOS scale scores were worse for patients using an assistive device but only declined weakly with increasing comorbid conditions. While all knee-specific scales discriminated between BSW groups, the KOOS quality of life (QOL) scale was significantly better (P < 0.05) than all measures except the SF-36 physical component summary. KOOS QOL also had the highest effect size, while SF-36 measures had lower effect sizes and standardized response means. KOOS pain and symptoms scales discriminated better than WOMAC pain and stiffness scales among BSW groups.

CONCLUSION: KOOS scales were valid and responsive in this cohort of US TKR patients. KOOS QOL performed particularly well in capturing aggregate knee-specific outcomes.

Predicting Mortality of Ruptured Abdominal Aortic Aneurysms in the Era of Endovascular Repair

Wed, 05/31/2017 - 11:45pm

BACKGROUND: Previous risk prediction models of mortality after ruptured abdominal aortic aneurysm (rAAA) repair have been limited by imprecision, complexity, or inclusion of variables not available in the preoperative setting. Most importantly, these prediction models have been derived and validated before the adoption of endovascular aneurysm repair (EVAR) as a treatment for rAAA. We sought to derive and validate a new risk-prediction tool using only easily obtainable preoperative variables in patients with rAAA who are being considered for repair in the endovascular era. METHODS: We used the Vascular Study Group of New England (VSGNE) database to identify all patients who underwent repair of RAAA (2006-2015). Variables were entered into a multivariable logistic regression model to identify independent predictors of 30-day mortality. Linear regression was then used to develop an equation to predict risk of 30-day mortality. RESULTS: During the study period, 649 patients underwent repair of rAAA; of these, 247 (38.1%) underwent EVAR and 402 (61.9%) underwent an open repair. The overall mortality associated with rAAA was 30.7% (open, 33.4% and EVAR, 26.2%). On multivariate modeling, the primary determinants of 30-day mortality were advanced age (>76 vs. 1.5 mg/dL vs. /=70 mm Hg, OR = 2.65 and CI: 1.79-3.92). The logistic regression model had an area under a c-statistic of 0.69. The corresponding linear model used to provide a point estimate of 30-day mortality (%) was % mortality = 14 + 22 * (age >76) + 9 * (creatinine >1.5) + 20 * (bp <70) Using this model, patients can be stratified into different groups, each with a specific estimated risk of 30-day mortality ranging from a low of 14% to a high of 65%. CONCLUSIONS: In the endovascular era where both open and endovascular treatment are offered for the treatment of rAAA three variables, easily obtained in an emergency setting, accurately predict 30-day mortality for patients operated on for rAAA. This simple risk prediction tool could be used as a point of care decision aid to help the clinician in counseling patients and their families on treatment of those presenting with rAAA.

Impact and Duration of Brief Surgeon-Delivered Smoking Cessation Advice on Attitudes Regarding Nicotine Dependence and Tobacco Harms for Patients with Peripheral Arterial Disease

Wed, 05/31/2017 - 11:44pm

BACKGROUND: Despite the recognized benefits of smoking cessation, many clinicians question if a brief smoking cessation intervention can help dedicated smokers with peripheral arterial disease understand nicotine dependence and harms related to smoking. We investigated the impact and durability of a multimodal smoking cessation intervention on patient attitudes regarding nicotine dependence and the health effects of smoking.

METHODS: We conducted a pilot cluster-randomized trial of a brief smoking cessation intervention at 8 vascular surgery practices between September 1, 2014 and August 31, 2015. Compared with control sites, patients at intervention sites received protocolized brief cessation counseling, medications, and referrals to a quitline. After their clinic visit and again at 3 months, participants completed a brief survey about patient attitudes regarding nicotine dependence and the health effects of smoking. Responses to questions were analyzed using chi-squared test and Student's t-test.

RESULTS: All trial participants (n = 156) complete the initial survey, and 75 (45%) participants completed the follow-up survey. Intervention and control patients both reported a greater than 30-pack-year history (80% vs. 90%, P = 0.07) and previous failed quit attempts (77% vs. 78%, P = 0.8). Compared with usual care, patients in the intervention group were more likely to describe hearing advice to quit from their surgeon (98% vs. 77%, P < 0.001), and expressed "a lot" or "some" interest in quitting (95.4% vs. 85.7%, P = 0.05). Patients in the intervention group were also more likely to acknowledge their addictive behaviors, consistently scoring higher on question bank items regarding nicotine addiction (52.9 vs. 48.0, P = 0.006) and the negative health effects of smoking (scaled score 56.6 vs. 50.6, P = 0.001). When resurveyed 3 months after intervention, patients in the intervention group had larger declines in nicotine dependence and health effect domains, suggesting durable impact of the intervention on patient attitudes regarding nicotine addiction and smoking harms.

CONCLUSIONS: Brief smoking cessation counseling by a vascular surgeon increases patient interest in smoking cessation and awareness of smoking harms, and this effect was durable 3 months after intervention. This evidence suggests that even brief counseling within a surgical clinic has the potential to impact patient desire to quit.

Determinants of Follow-Up Failure in Patients Undergoing Vascular Surgery Procedures

Wed, 05/31/2017 - 11:44pm

BACKGROUND: The Vascular Study Group of New England (VSGNE) requires documentation of follow-up for >80% of patients at least 9 months postprocedure. However, many participating groups fall short of this goal. We sought to identify factors independently associated with loss to long-term follow-up (LTF).

METHODS: The VSGNE was queried from 2008 to 2012, for all carotid endarterectomy (CEA), endovascular aneurysm repair (EVAR), open abdominal aortic aneurysm repair (OPEN), infrainguinal bypass (INFRA), and suprainguinal bypass (SUPRA) procedures in patients who survived greater than 9 months postprocedure. Our primary endpoint was loss to LTF, with LTF defined as documentation of a phone call or office visit >/=9 months postprocedure. Multivariable logistic regression was used to identify independent predictors of loss to LTF. Covariates included patient and procedural characteristics, and treatment center/physician. Relative contributions of covariates to the model were assessed by evaluation of the relative model Wald chi-squared values.

RESULTS: We identified 14,452 procedures (6567 CEA, 2391 EVAR, 3356 INFRA, 979 OPEN, and 1159 SUPRA). Of those, 4669 (32%) were lost to LTF. Rates of loss to LTF varied by center, and ranged from 9.8% to 100%. Independent predictors of loss to LTF were history of coronary artery disease or percutaneous coronary artery intervention (odds ratio [OR] 1.4, 95% confidence interval [CI] 1.1-1.7), procedure type (OPEN, OR 1.4, 95% CI: 1.2-1.7; CEA, OR 1.2, 95% CI: 1.1-1.4; referent, EVAR), and discharge to rehab (OR 1.2, 95% CI: 1.1-1.4; referent, home). Center variation was the strongest determinant of loss to LTF with a model chi2 over 40 times as large as the second strongest determinant.

CONCLUSIONS: LTF is central to outcome reporting and is vital to the success of any registry effort. In the VSGNE experience, center variation is the strongest predictor of loss to LTF, outweighing patient and procedural factors. Other predictors of loss to LTF included history of coronary revascularization, procedure type, no prior history of congestive heart failure, and discharge location. High performing centers likely have specific process measures that decrease loss to LTF. As the Society for Vascular Surgery Vascular Quality Initiative continues to roll out nationally, high performing centers in VSGNE should be studied to document and propagate best practices for minimizing loss to LTF.

Regional Variation in Postoperative Myocardial Infarction in Patients Undergoing Vascular Surgery in the United States

Wed, 05/31/2017 - 11:44pm

BACKGROUND: The aim of this study is to assess for regional variation in the incidence of postoperative myocardial infarction (POMI) following nonemergent vascular surgery across the United States to identify potential areas for quality improvement initiatives.

METHODS: We evaluated POMI rates across 17 regional Vascular Quality Initiative (VQI) groups that comprised 243 centers with 1,343 surgeons who performed 75,057 vascular operations from 2010 to 2014. Four procedures were included in the analysis: carotid endarterectomy (CEA, n = 39,118), endovascular abdominal aortic aneurysm (AAA) repair (EVAR, n = 15,106), infrainguinal bypass (INFRA, n = 17,176), and open infrarenal AAA repair (OAAA, n = 3,657). POMI was categorized by the method of diagnosis as troponin-only or clinical/ECG and rates were investigated in regions with >/=100 consecutive cases. Regions with significantly different POMI rates were defined as those >1.5 interquartile lengths beyond the 75th percentile of the distribution. Risk-adjusted rates of POMI were assessed using the VQI Cardiac Risk Index all-procedures prediction model to compare the observed versus expected rates for each region.

RESULTS: Overall rates of POMI varied by procedure type: CEA 0.8%, EVAR 1.1%, INFRA 2.7%, and OAAA 4.2% (P < 0.001). Significant variation in POMI rates was observed between regions, resulting in differing ranges of POMI rates for each procedure: CEA 0.5-2.0% (P = 0.001), EVAR 0.3-3.1% (P < 0.001), INFRA 1.1-4.8% (P < 0.001), and OAAA 2.2-10.0% (P < 0.001). A single region in 3 of the 4 procedure-specific datasets was identified as a statistical outlier with a significantly higher POMI rate after CEA, EVAR, and OAAA; this region was identical for the EVAR and OAAA datasets but was a different region for the CEA dataset. No significant variation in POMI was noted between regions after INFRA. Procedure-specific clinical POMI rates (mean; range) were significantly different between regions for EVAR (0.4%; 0-1.1%, P = 0.01) and INFRA (1.4%; 0.5-2.9%, P = 0.01), but not for CEA (0.4%; 0-0.8%, P = 0.53) or OAAA (1.6%; 0-3.8%, P = 0.23). Procedure-specific troponin-only POMI rates (mean; range) were significantly different between regions for all procedures: CEA (0.4%; 0.1-1.2%, P < 0.001), EVAR (0.7%; 0-2.1%, P < 0.001), INFRA (1.3%; 0.4-2.5%, P = 0.001), and OAAA (2.5%; 0-8.5%, P < 0.001). After risk adjustment, regional variation was again noted with 3 regions having higher and 4 regions having lower than expected rates of POMI.

CONCLUSIONS: Significant variation in POMI rates following major vascular surgery exists across VQI regions even after risk adjustment. These findings may present an opportunity for focused regional quality improvement efforts.

Detection of non-CLL-like monoclonal B cell lymphocytosis increases dramatically in the very elderly, while detection of CLL-like populations varies by race: findings in a multiethnic population-based cohort of elderly women

Wed, 05/31/2017 - 11:44pm

Monoclonal B cell lymphocytosis (MBL) is both a marker of immune senescence and a potential precursor of B cell malignancy. Most MBL populations have a chronic lymphocytic leukemia-like (CLL-like) immunophenotype, but those that are CD5-negative (non-CLL-like) are also recognized and may represent a distinct diagnostic entity. To date, MBL studies have taken place in relatively homogenous populations, although risk of CLL varies across racial groups and geographic regions. We report flow cytometry data from 597 ethnically diverse 64-94-year-old women from across the USA who are participants in the Women's Health Initiative (WHI) Long-Life Study (LLS). Overall, MBL was detected in 26 % of the participants and included 20.9 % with a CLL-like immunophenotype, 5 % with a non-CLL-like immunophenotype, and 1.3 % with both. White and Hispanic women were more than twice as likely to have a CLL-like MBL population detected than African American women, corrected for age (P = 0.003). By contrast, detection of non-CLL-like MBL did not vary significantly by race, but did increase markedly with advancing age, being present in 12.7 % of those aged 85 and older. We provide new evidence that rates of detection of CLL-like MBL are lower in African Americans, and further suggest that non-CLL-like clonal expansions should be regarded as distinct from CLL-like MBL.

Persuasive Interventions for Controversial Cancer Screening Recommendations: Testing a Novel Approach to Help Patients Make Evidence-Based Decisions

Wed, 05/31/2017 - 11:44pm

PURPOSE: We wanted to evaluate novel decision aids designed to help patients trust and accept the controversial, evidence-based, US Preventive Services Task Force recommendations about prostate cancer screening (from 2012) and mammography screening for women aged 40 to 49 years (from 2009). METHODS: We created recorded vignettes of physician-patient discussions about prostate cancer screening and mammography, accompanied by illustrative slides, based on principles derived from preceding qualitative work and behavioral science literature. We conducted a randomized crossover study with repeated measures with 27 men aged 50 to 74 years and 35 women aged 40 to 49 years. All participants saw a video intervention and a more traditional, paper-based decision aid intervention in random order. At entry and after seeing each intervention, they were surveyed about screening intentions, perceptions of benefits and harm, and decisional conflict. RESULTS: Changes in screening intentions were analyzed without regard to order of intervention after an initial analyses showed no evidence of an order effect. At baseline, 69% of men and 86% of women reported wanting screening, with 31% and 6%, respectively, unsure. Mean change on a 3-point, yes, unsure, no scale was -0.93 (P = <.001) for men and -0.50 (P = <.001) for women after seeing the video interventions vs 0.0 and -0.06 (P = .75) after seeing the print interventions. At the study end, 33% of men and 49% of women wanted screening, and 11% and 20%, respectively, were unsure. CONCLUSIONS: Our novel, persuasive video interventions significantly changed the screening intentions of substantial proportions of viewers. Our approach needs further testing but may provide a model for helping patients to consider and accept evidence-based, counterintuitive recommendations.

Longevity of Genotype-Specific Immune Responses to Plasmodium falciparum Merozoite Surface Protein 1 in Kenyan Children from Regions of Different Malaria Transmission Intensity

Wed, 05/31/2017 - 11:44pm

Naturally acquired immunity to Plasmodium falciparum presents a changing landscape as malaria control programs and vaccine initiatives are implemented. Determining which immunologic indicators remain surrogates of past infection, as opposed to mediators of protection, led us to compare stability of immune responses across regions with divergent malaria transmission intensities. A repeat cross-sectional study of Kenyan children from a malaria-holoendemic area and an epidemic-prone area was used to examine longitudinal antibody and interferon-gamma (IFN-gamma) responses to the 3D7 and FVO variants of merozoite surface protein 1 (MSP1). Antibodies to MSP1 were common in both study populations and did not significantly wane over a 21-month time period. IFN-gamma responses were less frequent and rapidly disappeared in children after a prolonged period of no malaria transmission. Antibody and IFN-gamma responses rarely correlated with each other; however, MSP1-specific IFN-gamma response correlated with lack of concurrent P. falciparum parasitemia of the same genotype, though only statistically significantly in the malaria-holoendemic region (odds ratio = 0.31, 95% confidence interval = 0.12-0.84). This study affirms that antimalarial antibodies are informative for evaluation of history of malaria exposure within individuals, whereas cell-mediated immunity, though short lived under natural exposure conditions, might provide an assessment of recent infection and protection from parasitemia.

Maternal Age at Childbirth and Parity as Predictors of Longevity Among Women in the United States: The Women's Health Initiative

Wed, 05/31/2017 - 11:44pm

OBJECTIVES: To examine associations of maternal age at childbirth and parity with survival to age 90 years (longevity).

METHODS: We performed a prospective study among a multiethnic cohort of postmenopausal US women in the Women's Health Initiative recruited from 1993 to 1998 and followed through August 29, 2014. We adjusted associations with longevity for demographic, lifestyle, reproductive, and health-related characteristics.

RESULTS: Among 20 248 women (mean age at baseline, 74.6 years), 10 909 (54%) survived to age 90 years. The odds of longevity were significantly higher in women with later age at first childbirth (adjusted odds ratio = 1.11; 95% confidence interval = 1.02, 1.21 for age 25 years or older vs younger than 25 years; P for trend = .04). Among parous women, the relationship between parity and longevity was significant among White but not Black women. White women with 2 to 4 term pregnancies compared with 1 term pregnancy had higher odds of longevity.

CONCLUSIONS: Reproductive events were associated with longevity among women. Future studies are needed to determine whether factors such as socioeconomic status explain associations between reproductive events and longevity.

Life Years Gained From Smoking-Cessation Counseling After Myocardial Infarction

Wed, 05/31/2017 - 11:44pm

INTRODUCTION: Hospitalization for acute myocardial infarction (AMI) is an opportune time to counsel smokers to quit. Studies have demonstrated lower short-term mortality for counseled versus non-counseled smokers; yet, little is known about the long-term survival benefits of post-AMI smoking-cessation counseling (SCC).

METHODS: Data from the Cooperative Cardiovascular Project, a prospective cohort study of elderly patients with AMI between 1994 and 1996 with >17 years of follow-up, were used to evaluate the association of SCC with short- and long-term mortality in smokers with AMI. Life expectancy and years of potential life gained were used to quantify the long-term survival benefits of SCC. Cox proportional hazards models with exponential extrapolation were used to estimate life expectancy.

RESULTS: The analysis included 13,815 smokers, of whom 5,695 (41.2%) received SCC. Non-counseled smokers had higher crude mortality than counseled smokers over all 17 years of follow-up. After adjustment for patient and hospital characteristics, SCC was associated with a 22.6% lower 30-day mortality and a 7.5% lower mortality over 17 years. These survival differences produced higher life expectancy estimates for counseled smokers than non-counseled smokers at all ages, which resulted in average gains in life years of 0.13 (95% CI=-0.31, 0.56) to 0.58 (95% CI=0.25, 0.91) years, with the largest gains observed in older smokers.

CONCLUSIONS: SCC is associated with longer life expectancy and gains in life years in elderly smokers with AMI, supporting the importance of post-AMI counseling efforts.

Osteoporosis in the Women's Health Initiative: Another Treatment Gap

Wed, 05/31/2017 - 11:44pm

BACKGROUND: Osteoporotic fractures are associated with high morbidity, mortality, and cost.

METHODS: We performed a post hoc analysis of the Women's Health Initiative (WHI) clinical trials data to assess osteoporosis treatment and identify participant characteristics associated with utilization of osteoporosis medication(s) after new diagnoses of osteoporosis or fracture. Information from visits prior to and immediately subsequent to the first fracture event or osteoporosis diagnosis were evaluated for medication use. A full logistic regression model was used to identify factors predictive of osteoporosis medication use after a fracture or a diagnosis of osteoporosis.

RESULTS: The median length of follow-up from enrollment to the last WHI clinic visit for the study cohort was 13.9 years. Among the 13,990 women who reported new diagnoses of osteoporosis or fracture between enrollment and their final WHI visit, and also had medication data available, 21.6% reported taking an osteoporosis medication other than estrogen. Higher daily calcium intake, diagnosis of osteoporosis alone or both osteoporosis and fracture (compared with diagnosis of fracture alone), Asian or Pacific Islander race/ethnicity (compared with White/Caucasian), higher income, and hormone therapy use (past or present) were associated with significantly higher likelihood of osteoporosis pharmacotherapy. Women with Black/African American race/ethnicity (compared with White/Caucasian), body mass index >/=30 (compared with body mass index of 18.5-24.9), current tobacco use (compared with past use or lifetime nonusers), and history of arthritis were less likely to use osteoporosis treatment.

CONCLUSION: Despite well-established treatment guidelines in postmenopausal women with osteoporosis or history of fractures, pharmacotherapy use was suboptimal in this study. Initiation of osteoporosis treatment after fragility fracture may represent an opportunity to improve later outcomes in these high-risk women. Specific attention needs to be paid to increasing treatment among women with fragility fractures, obesity, current tobacco use, history of arthritis, or of Black race/ethnicity.

Changes in the inflammatory potential of diet over time and risk of colorectal cancer in postmenopausal women

Wed, 05/31/2017 - 11:44pm

We examined the associations between changes in dietary inflammatory potential and risk of colorectal cancer (CRC) in 87,042 postmenopausal women recruited from 1993-1998 into the Women's Health Initiative. Food frequency questionnaire data were used to compute patterns of change in dietary inflammatory index (DII) scores and cumulative average DII scores over 3 years. Cox regression models were used to estimate hazard ratios for CRC risk. After a median 16.2 years follow-up, 1,038 CRC cases were diagnosed. DII changes were not substantially associated with overall CRC, but proximal colon cancer risk was higher in the pro-inflammatory change DII compared to the anti-inflammatory stable DII groups (hazard ratio = 1.32; 95% confidence interval: 1.01, 1.74). Among non-users of nonsteroidal anti-inflammatory drugs (NSAID) (Pinteraction = 0.055) the pro-inflammatory stable DII group was at increased risk of overall CRC and proximal colon cancer. Also among non-users of NSAID, risks of overall CRC, colon cancer, and proximal colon cancer were higher in the highest quintile compared to the lowest cumulative average DII quintile (65%, 61%, and 91% increased risk, respectively). Dietary changes towards, or a history of, pro-inflammatory diets are associated with an elevated risk of colon cancer, particularly for proximal colon cancer and among non-users of NSAID.