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1.  Social Service Barriers Delay Care Among Women with Abnormal Cancer Screening 
Inequity in cancer outcomes for minorities and vulnerable populations has been linked to delays in cancer care that arise from barriers to accessing care. Social service barriers represent those obstacles related to meeting life’s most basic needs, like housing and income, which are often supported by public policy, regulation and services.
To examine the association between social service barriers and timely diagnostic resolution after a cancer screening abnormality.
Secondary analysis of the intervention arm of Boston Patient Navigation Research Program (2007–2008) conducted across six urban community health centers. Subjects with no barriers, other barriers, and social service barriers were compared on their time to diagnostic resolution.
Women ≥ 18 years of age with a breast or cervical cancer screening abnormality.
Social service barriers included: income supports, housing and utilities, education and employment, and personal/family stability and safety. Time to event analyses compared across five groups: those with no barriers, one barrier (other), one barrier (social service), two or more barriers (all other), and two or more barriers (at least one social service).
1,481 navigated women; 31 % Hispanic, 27 % Black, 32 % White; 37 % non-English speakers and 28 % had private health insurance. Eighty-eight women (6 %) had social service barriers. Compared to those without social service barriers, those with were more likely to be Hispanic, younger, have public/no health insurance, and have multiple barriers. Those with two or more barriers (at least one social service barrier), had the longest time to resolution compared to the other four groups (aHR resolution < 60 days = 0.27, ≥ 60 days = 0.37).
Vulnerable women with multiple barriers, when at least one is a social service barrier, have delays in care despite navigation. The impact of patient navigation may never be fully realized if social service barriers persist without being identified or addressed.
PMCID: PMC3889949  PMID: 24197626
access to care; cancer; disparities; vulnerable populations
2.  Prediction of the location and size of the stomach using patient characteristics for retrospective radiation dose estimation following radiotherapy 
Physics in medicine and biology  2013;58(24):8739-8753.
Following cancer radiotherapy, reconstruction of doses to organs, other than the target organ, is of interest for retrospective health risk studies. Reliable estimation of doses to organs that may be partially within or fully outside the treatment field requires reliable knowledge of the location and size of the organs, e.g., the stomach, which is at risk from abdominal irradiation. The stomach location and size are known to be highly variable between individuals, but have been little studied. Moreover, for treatments conducted years ago, medical images of patients are usually not available in medical records to locate the stomach. In light of the poor information available to locate the stomach in historical dose reconstructions, the purpose of this work was to investigate the variability of stomach location and size among adult male patients and to develop prediction models for the stomach location and size using predictor variables generally available in medical records of radiotherapy patients treated in the past. To collect data on stomach size and position, we segmented the contours of the stomach and of the skeleton on contemporary Computed Tomography (CT) images for 30 male patients in supine position. The location and size of the stomach was found to depend on body mass index (BMI), ponderal index (PI), and age. For example, the anteroposterior dimension of the stomach was found to increase with increasing BMI (≈0.25 cm per kg/m2) whereas its craniocaudal dimension decreased with increasing PI (≈ −3.3 cm per kg/m3) and its transverse dimension increased with increasing PI (≈ 2.5 cm per kg/m3). Using the prediction models, we generated three dimensional computational stomach models from a deformable hybrid phantom for three patients of different BMI. Based on a typical radiotherapy treatment, we simulated radiotherapy treatments on the predicted stomach models and on the CT images of the corresponding patients. Those dose calculations demonstrated good agreement between predicted and actual stomachs compared with doses derived from a reference model of the body that might be used in the absence of individual CT scan data.
PMCID: PMC4160803  PMID: 24301086
stomach; size and location; predictive models; radiation dose
3.  Increased Risk of Recurrent Gout Attacks with Hospitalization 
The American journal of medicine  2013;126(12):10.1016/j.amjmed.2013.06.026.
While anecdotal evidence suggests that risk of recurrent gout attack increases with hospitalization, no study has formally tested this hypothesis.
We conducted an online case-crossover study of individuals with gout. We obtained information on gout attacks over a one-year period, including: onset date, symptoms and signs, medications, and exposure to potential risk factors, including hospitalization, during the 2-day hazard period prior to each gout attack. The same exposure information was also obtained over 2-day intercritical gout control periods. We performed conditional logistic regression to examine the relationship of hospitalization with recurrent gout attacks and whether such a relationship was modified by concomitant use of anti-gout medications.
Of 724 participants (mean age 54.5 years, 78.5% male), 35 hospitalizations occurred during either a hazard or control period. The adjusted odds of gout attacks was increased 4-fold with hospitalization (OR 4.05, 95% confidence interval: 1.78–9.19) compared with no hospitalization. The effect of hospitalization tended to attenuate with use of allopurinol, colchicine, or NSAIDs, but not statistically significantly.
Our study confirmed that the risk of gout attacks increases among gout patients during hospitalization. Appropriate measures should be considered for prevention of gout attacks during hospitalization for patients with pre-existing gout.
PMCID: PMC3838663  PMID: 24054179
4.  Multi-tracer PET imaging of bone metastases from paraganglioma: peripheral halo of uptake on 18F-FLT PET mismatching with central uptake of 18F-FDOPA, 18F-Fdopamine, and 18F-FDG 
European journal of nuclear medicine and molecular imaging  2013;40(12):10.1007/s00259-013-2507-7.
PMCID: PMC3840388  PMID: 23880966
pheochromocytoma and paraganglioma; bone metastases; PET/CT; 18F-fluorothymidine; 18F-fluorodeoxyglucose; cell proliferation
5.  99mTc-labeled Therapeutic Inhaled Amikacin Loaded Liposomes 
Journal of liposome research  2013;23(4):336-342.
The radiolabeling of the liposome surface can be a useful tool for in vivo tracking of therapeutic drug loaded liposomes. We investigated radiolabeling therapeutic drug (i.e., an antibiotic, amikacin) loaded liposomes with 99mTc, nebulization properties of 99mTc-labeled liposomal amikacin for inhalation (99mTc-LAI), and its stability by size exclusion low pressure liquid chromatography (LPLC). LAI was reacted with 99mTc using SnCl2 dissolved in ascorbic acid as a reducing agent for 10 min at room temperature. The labeled products were then purified by anion exchange resin. The purified 99mTc-LAI in 1.5% NaCl solution was incubated at 4oC to assess its stability by LPLC. The purified 99mTc-LAI was subjected to studies with a clinically used nebulizer (PARI eFlow®) and the Anderson Cascade Impactor (ACI). The use of ascorbic acid at 0.91 mM resulted in a quantitative labeling efficiency. The LPLC profile showed that the liposomal peak of LAI detected by a UV monitor at both 200 nm and 254 nm overlapped with the radioactivity peak of 99mTc-LAI, indicating that 99mTc-LAI is suitable for tracing LAI. The ACI study demonstrated that the aerosol droplet size distribution determined gravimetrically was similar to that determined by radioactivity. The liposome surface labeling method using SnCl2 in 0.91mM ascorbic acid produced 99mTc-LAI with a high labeling efficiency and stability that are adequate to evaluate the deposition and clearance of inhaled LAI in the lung by gamma scintigraphy.
PMCID: PMC4231483  PMID: 23879241
99mTc-labeled liposome-encapsulated amikacin; radiolabeling; size exclusion analysis
6.  Prevalence of Advanced Colorectal Neoplasia in Whites and Blacks Undergoing Screening Colonoscopy in a Safety Net Hospital 
Annals of internal medicine  2013;159(1):13-20.
Blacks are more likely than whites to be diagnosed with colorectal cancer and die of their disease. The extent to which genetic or biologic factors versus disparities in screening rates explain this variance remains controversial.
To define the prevalence and location of presymptomatic advanced colorectal neoplasia (ACN) among whites and blacks undergoing screening colonoscopy controlling for other epidemiologic determinants of risk.
Cross-sectional survey between March 22, 2005 and January 31, 2012.
Urban, open-access, academic, safety net hospital in Massachusetts.
Asymptomatic, average-risk whites (n=1172) and blacks (n=1681) 50 to 79 years of age presenting for screening colonoscopy.
Adjusted prevalence and location of ACN, defined as a tubular adenoma ≥ 10 mm in size, any adenoma with villous features or high-grade dysplasia, any dysplastic serrated lesion, or invasive cancer.
The prevalence of ACN was higher among whites than blacks (6.8% vs. 5.0%; P=0.039) but varied by sex (white versus black men, 9.3% vs. 5.7%; white vs. black women, 3.5% vs. 4.3%; P for interaction =0.034). After controlling for exposure to multiple risk factors, black men were 41% less likely than white men (adjusted odds ratio [aOR], 0.59; 95% confidence intervals [CI], 0.39–0.89) to have ACN; conversely, no significant differences were observed for women (aOR, 1.32; 95% CI, 0.73–2.40). Among individuals with ACN, blacks a higher percentage of proximal disease (52% vs. 39%) after adjustment for age and sex (P=0.055).
Single institution study; inadequate statistical power for subgroup analyses; recall bias.
Black men are less likely than white men to have ACN at screening colonoscopy in a safety net health care setting. These findings suggest that disparities in access to screening and differential exposure to modifiable risk factors rather than genetic or biologic factors are largely responsible for the higher incidence of CRC among black men. Genetic or biologic factors, however may explain the predilection for proximal disease.
Primary Funding Source
National Cancer Institute
PMCID: PMC4218749  PMID: 23817700
7.  Current and future trends in the anatomic and functional imaging of head and neck paragangliomas 
Seminars in nuclear medicine  2013;43(6):462-473.
Head and neck paragangliomas (HNPGLs) account for approximately 3% of all paragangliomas (PGLs). Most often, HNPGLs are benign, non-secreting, and slowly progressing. The initial physical examination and biochemical diagnosis usually adds very little to the proper diagnosis of these tumors and therefore, radiologists and nuclear medicine physicians play the pivotal role in providing the initial diagnosis, the locoregional staging, and the plan for detecting potential multicentric or metastatic lesions. Based on several current studies, the most accurate use of HNPGL-specific initial and subsequent imaging modalities must be guided by the knowledge of genetics and the specifically measured biochemical profile of these tumors for the proper management of these patients. Thus, this short review article presents the application of the most up-to-date anatomic and functional imaging approaches to HNPGLs tightly linked to the clinical management of these patients. Based on the most recent studies, 18F-FDOPA PET/CT has been shown to be a useful addition to anatomic imaging in the preoperative localization and molecular assessment of HNPGLs. It is estimated that the frequency of metabolically active PGLs on 18F-FDOPA PET/CT in this region is higher than 90%. 18F-FDG PET/CT should be reserved for patients with hereditary PGL syndromes. Imaging of somatostatin receptors using Octreoscan or 68Ga-labeled somatostatin analogs plays an important role for selecting patients for targeted radiation therapy.
This review also concludes that it is expected that in the near future, these patients will indeed benefit from new diagnostic approaches based on the identification of new targets by molecular profiling studies that will result in the development of novel PGL specific radiopharamceuticals.
PMCID: PMC3792493  PMID: 24094713
Positron emission tomography; computed tomography; paraganglioma; radiopharmaceuticals; genetics; head and neck
8.  Impact of Depression on the Intensity of Patient Navigation for Women with Abnormal Cancer Screenings 
Patient navigation is increasingly being used to support vulnerable patients to receive timely and quality medical care. We sought to understand whether patients with depression utilize additional patient navigation services after abnormal cancer screening. We compared depressed and non-depressed women using three different measures of intensity of patient navigation: number of patient-navigator encounters, encounter time, and number of unique barriers to care. The study population consisted of 1,455 women who received navigation after abnormal screening for breast or cervical cancer at one of six community health centers in Boston. Navigators spent a median of 60–75 minutes over one or two encounters per participant, with 49% of participants having one or more documented barrier to care. Depressed women did not differ in total numbers of encounters, encounter time, or unique barriers compared with non-depressed women. Our findings suggest that pre-existing depression does not predict which women will utilize additional navigation services.
PMCID: PMC4184058  PMID: 24509033
Patient navigation; depression; women’s health; cancer screening; navigation intensity
9.  Functional characterization of non-metastatic paraganglioma and pheochromocytoma by 18F-FDOPA PET: focus on missed lesions 
Clinical endocrinology  2013;79(2):170-177.
Aims and methods
To evaluate the clinical value of 18F-fluorodihydroxyphenylalanine (18F-FDOPA) PET in relation to tumour localization and the patient’s genetic status in a large series of pheochromocytoma/paraganglioma (PHEO/PGL) patients and to discuss in detail false-negative results.
A retrospective study of PGL patients who were investigated with 18F-FDOPA PET or PET/CT imaging in two academic endocrine tumour centers was conducted (La Timone University Hospital, Marseilles, France and National Institutes of Health (NIH), Bethesda, MD, USA).
One hundred sixteen patients (39.7% harboring germline mutations in known disease susceptibility genes) were evaluated for a total of 195 PHEO/PGL foci. 18F-FDOPA PET correctly detected 179 lesions (91.8%) in 107 patients (92.2%).
Lesion-based sensitivities for parasympathetic PGLs (head, neck, or anterior/middle thoracic ones), PHEOs, and extra-adrenal sympathetic (abdominal or posterior thoracic) PGLs were 98.2% [96.5% for Timone and 100% for NIH], 93.9% [93.8% and 93.9%], and 70.3% [47.1% and 90%], respectively (P<0.001).
Sympathetic (adrenal and extra-adrenal) SDHx-related PGLs were at a higher risk for negative 18F-FDOPA PET than non-SDHx-related PGLs (14/24 vs 0/62, respectively, p<0.001). By contrast, the risk of negative 18F-FDOPA PET was lower for parasympathetic PGLs regardless of the genetic background (1/90 in SDHx vs 1/19 in non-SDHx tumours, p= 0.32).
18F-FDOPA PET failed to detect 2 head and neck PGLs (HNPGL), likely due to their small size, while most missed sympathetic PGL were larger and may have exhibited a specific 18F-FDOPA-negative imaging phenotype. 18F-FDG PET detected all the missed sympathetic lesions.
18F-FDOPA PET appears to be a very sensitive functional imaging tool for HNPGL regardless of the genetic status of the tumours. Patients with false-negative tumours on 18F-FDOPA PET should be tested for SDHx mutations.
PMCID: PMC3610811  PMID: 23230826
Positron emission tomography; 18F-fluorodihydroxyphenylalanine; paraganglioma; radiopharmaceuticals; genetics
10.  Tumor Localization and Biochemical Response to Cure in Tumor-Induced Osteomalacia 
Tumor-induced osteomalacia (TIO) is a rare disorder of phosphate wasting due to fibroblast growth factor-23 (FGF23)-secreting tumors that are often difficult to locate. We present a systematic approach to tumor localization and post-operative biochemical changes in 31 subjects with TIO. All had failed either initial, or re-localization (in case of recurrence or metastases at outside institutions). Functional imaging with 111Indium-octreotide with single photon emission computed tomography (octreo-SPECT or SPECT/CT), and 18fluorodeoxyglucose positron emission tomography/CT (FDG-PET/CT) were performed, followed by anatomic imaging (CT,MRI). Selective venous sampling (VS) was performed when multiple suspicious lesions were identified or high surgical risk was a concern. Tumors were localized in 20/31 subjects (64.5%). Nineteen of 20 subjects underwent octreo-SPECT imaging, and 16/20 FDG-PET/CT imaging. Eighteen of 19 (95%) were positive on octreo-SPECT, and 14/16 (88%) on FDG-PET/CT. Twelve of 20 subjects underwent VS; 10/12 (83%) were positive. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were: sensitivity=0.95, specificity=0.64, PPV=0.82 and NPV=0.88 for octreo-SPECT; sensitivity=0.88, specificity=0.36, PPV=0.62 and NPV=0.50 for FDG-PET/CT. Fifteen subjects had their tumor resected at our institution, and were disease-free at last follow-up. Serum phosphorus returned to normal in all subjects within 1-5 days. In 10 subjects who were followed for at least 7 days postoperatively, intact FGF23 (iFGF23) decreased to near undetectable within hours and returned to the normal range within 5 days. C-terminal FGF23 (cFGF23) decreased immediately but remained elevated, yielding a markedly elevated cFGF23/iFGF23 ratio. Serum 1,25-dihydroxyvitamin D3 (1,25D) rose and exceeded the normal range. In this systematic approach to TIO tumor localization Octreo-SPECT was more sensitive and specific, but in many cases FDG-PET/CT was complementary. VS can discriminate between multiple suspicious lesions and increase certainty prior to surgery. Sustained elevations in cFGF23 and 1,25D were observed, suggesting novel regulation of FGF23 processing and 1,25D generation.
PMCID: PMC3900247  PMID: 23362135
FGF23; hypophosphatemia; mineral metabolism; vitamin D
11.  Molecular Imaging of Neuroendocrine Tumors 
Seminars in oncology  2010;37(6):662-679.
Neuroendocrine tumors (NET) are a heterogeneous group of tumors that arise from neuroendocrine cells. These tumors may arise from various organs, including lung, thymus, thyroid, stomach, duodenum, small bowel, large bowel, appendix, pancreas, adrenal, and skin. Most are well differentiated and have the ability to produce biogenic amines and various hormones. NET usually occur sporadically but they also be associated with various familial syndromes. For the vast majority of NET, surgical resection is the treatment of choice whenever feasible. Localization of NET prior to surgery and for staging and follow-up relies on both anatomic and functional imaging modalities. In fact, the unique secretory characteristics of these tumors lend themselves to imaging by molecular imaging modalities, which can target specific metabolic pathways or receptors. Neuroendocrine cells have a variety of such target receptors and pathways for which radiopharmaceuticals have been developed, including [123I/131I]-metaiodobenzylguanidine (MIBG), [ 111In]pentetreotide, [68Ga] somatostatin analogs, [18F] fluorodeoxyglucose (FDG), [11C/18F] dihydroxyphenylalanine (DOPA), [11C] 5-hydroxytryptophan (5-HTP) 99mTc pentavalent dimercaptosuccinic acid ([99mTc] (V) DMSA, and [18F] fluorodopamine (FDA). Here, we review the molecular imaging approaches for NET using various radiopharmaceuticals.
PMCID: PMC4003904  PMID: 21167384
12.  Aid-Assisted Decision-Making and Colorectal Cancer Screening 
Shared decision-making (SDM) is a widely recommended yet unproven strategy for increasing colorectal cancer (CRC) screening uptake. Previous trials of decision aids to increase SDM and CRC screening uptake have yielded mixed results.
To assess the impact of decision aid–assisted SDM on CRC screening uptake.
The study was conducted at an urban, academic safety-net hospital and community health center between 2005 and 2010. Participants were asymptomatic, average-risk patients aged 50–75 years due for CRC screening.
Study participants (n=825) were randomized to one of two intervention arms (decision aid plus personalized risk assessment or decision aid alone) or control arm. The interventions took place just prior to a routine office visit with their primary care providers.
Main outcome measures
The primary outcome was completion of a CRC screening test within 12 months of the study visit. Logistic regression was used to identify predictors of test completion and mediators of the intervention effect. Analysis was completed in 2011.
Patients in the decision-aid group were more likely to complete a screening test than control patients (43.1% vs 34.8%; p=0.046) within 12 months of the study visit; conversely, test uptake for the decision aid and decision aid plus personalized risk assessment arms was similar (43.1% vs 37.1%; p=0.15). Assignment to the decision-aid arm (AOR 1.48; 95% CI=1.04, 2.10), black race (AOR 1.52, 95% CI=1.12, 2.06) and a preference for a patient-dominant decisionmaking approach (AOR, 1.55; 95% CI=1.02, 2.35) were independent determinants of test completion. Activation of the screening discussion and enhanced screening intentions mediated the intervention effect.
Decision aid–assisted SDM has a modest impact on CRC screening uptake. A decision aid plus personalized risk assessment tool is no more effective than a decision aid alone.
PMCID: PMC3966107  PMID: 23159252
13.  Purine-rich foods intake and recurrent gout attacks 
Annals of the rheumatic diseases  2012;71(9):1448-1453.
To examine and quantify the relation between purine intake and the risk of recurrent gout attacks among gout patients.
The authors conducted a case-crossover study to examine associations of a set of putative risk factors with recurrent gout attacks. Individuals with gout were prospectively recruited and followed online for 1 year. Participants were asked about the following information when experiencing a gout attack: the onset date of the gout attack, clinical symptoms and signs, medications (including antigout medications), and presence of potential risk factors (including daily intake of various purine-containing food items) during the 2-day period prior to the gout attack. The same exposure information was also assessed over 2-day control periods.
This study included 633 participants with gout. Compared with the lowest quintile of total purine intake over a 2-day period, OR of recurrent gout attacks were 1.17, 1.38, 2.21 and 4.76, respectively, with each increasing quintile (p for trend <0.001). The corresponding OR were 1.42, 1.34, 1.77 and 2.41 for increasing quintiles of purine intake from animal sources (p for trend <0.001), and 1.12, 0.99, 1.32 and 1.39 from plant sources (p=0.04), respectively. The effect of purine intake persisted across subgroups by sex, use of alcohol, diuretics, allopurinol, NSAIDs and colchicine.
The study findings suggest that acute purine intake increases the risk of recurrent gout attacks by almost fivefold among gout patients. Avoiding or reducing amount of purine-rich foods intake, especially of animal origin, may help reduce the risk of gout attacks.
PMCID: PMC3889483  PMID: 22648933
14.  Epidemiology, Treatment Patterns, and Outcomes of Metastatic Soft Tissue Sarcoma in a Community-Based Oncology Network 
Sarcoma  2014;2014:145764.
Purpose. To assess epidemiology, treatment patterns, and outcomes of metastatic soft tissue sarcoma (mSTS) patients in USA community oncology practices. Methods. This retrospective, descriptive study used US Oncology's iKnowMed electronic health records database. Adults (≥18 years) with mSTS and at least two visits between July 2007 and June 2010 were included. Key outcomes were practice patterns, overall survival (OS), and progression-free survival (PFS). Results. 363 mSTS patients (174 treated and 189 untreated) met the prespecified exclusion/inclusion criteria. The most common subtypes were leiomyosarcoma (n = 104; 29%), liposarcoma (n = 40; 11%), and synovial sarcoma (n = 12; 3%); the remainder (n = 207; 57%) comprised 27 histologic subtypes. Treated patients were younger and had lower ECOG scores; 75% and 25% received first-line combination or monotherapy, respectively. Median OS of treated and untreated patients was 22 and 17 months, respectively, and 29 months in patients with the three most common subtypes. Before controlling for effects of covariates, younger age and lower ECOG scores were associated with better OS and PFS. Conclusion. This study provides insights into mSTS epidemiology, treatment patterns, and outcomes in a large community-based oncology network. These results warrant further studies with larger cohorts.
PMCID: PMC3942092  PMID: 24683310
15.  Cherry Consumption and the Risk of Recurrent Gout Attacks 
Arthritis and rheumatism  2012;64(12):4004-4011.
To study the relation between cherry intake and the risk of recurrent gout attacks among individuals with gout.
We conducted a case-crossover study to examine associations of a set of putative risk factors with recurrent gout attacks. Individuals with gout were prospectively recruited and followed online for one year. Participants were asked about the following information when experiencing a gout attack: the onset date of the gout attack, symptoms and signs, medications (including anti-gout medications), and potential risk factors (including daily intake of cherries and cherry extract) during the 2-day period prior to the gout attack. We assessed the same exposure information over 2-day control periods. We estimated the risk of recurrent gout attacks related to cherry intake using conditional logistic regression.
Our study included 633 individuals with gout. Cherry intake over a 2-day period was associated with a 35% lower risk of gout attacks compared with no intake (multivariate odds ratio [OR] = 0.65, 95% CI: 0.50-0.85). Cherry extract intake showed a similar inverse association (multivariate OR=0.55, 95% CI: 0.30-0.98). The effect of cherry intake persisted across subgroups by sex, obesity status, purine intake, alcohol use, diuretic use, and use of anti-gout medications. When cherry intake was combined with allopurinol use, the risk of gout attacks was 75% lower than periods without either exposure (OR=0.25, 95% CI: 0.15-0.42).
These findings suggest that cherry intake is associated with a lower risk of gout attacks.
PMCID: PMC3510330  PMID: 23023818
Cherry; gout; case-crossover study
16.  Evaluating Use Characteristics for the Oncotype Dx 21-Gene Recurrence Score and Concordance With Chemotherapy Use in Early-Stage Breast Cancer 
Journal of Oncology Practice  2013;9(4):182-187.
Patients who are younger, have better ECOG performance status, or have higher grade tumors are more likely to undergo recurrence score testing.
Oncotype Dx 21-gene assay recurrence score (RS) predicts recurrence of early-stage breast cancer (ESBC). We investigated whether patient, tumor, or practice characteristics drive its use and explored Oncotype DX RS and chemotherapy use in subgroups.
Patients with ESBC with documented estrogen receptor–positive, lymph node–negative, human epidermal growth factor receptor 2–negative tumors registered within McKesson Specialty Health's iKnowMed electronic health record were included. Patient and practice characteristics by region and size were analyzed. The association between Oncotype DX RS value and use of chemotherapy were assessed.
The study included 6,229 patients. Of these, 1,822 (29%) had an Oncotype DX RS result. Test use was 36%, 38%, 34%, 25%, and 6%, respectively, in patients age ≤ 45, 46-55, 56-65, 66-75, and ≥ 76 years; 33%, 25%, and 9% in patients with Eastern Cooperative Oncology Group performance status of 0, 1, and ≥ 2; 7%, 9%, 25%, 38%, 27%, and 10% in T1mic, T1a, T1b, T1c, T2, and T3 tumors; and 26%, 32%, and 33% for grades 1, 2, and 3 tumors. Of the 1,822 patients with available Oncotype DX RS, adjuvant chemotherapy use was 6%, 42%, and 84% in the low-, intermediate-, and high-risk groups.
Patients who were younger, had better ECOG performance status, or had higher grade tumors were more likely to undergo RS testing. It appears that the RS test may have influenced the decision about whether to administer adjuvant chemotherapy: a low RS score was associated with lower chemotherapy use and a high RS score was associated with higher chemotherapy use.
PMCID: PMC3710166  PMID: 23942918
17.  BOSTON PATIENT NAVIGATION RESEARCH PROGRAM: The Impact of Navigation on Time to Diagnostic Resolution after Abnormal Cancer Screening 
There is a need for controlled studies to assess the impact of patient navigation in vulnerable cancer populations.
Boston Patient Navigation Research Program conducted a quasi-experimental patient navigation intervention across six federally qualified inner-city community health centers, three assigned to a breast cancer navigation intervention and three assigned to a cervical cancer navigation intervention; each group then served as the control for the other. Eligible women had an abnormal breast or cervical cancer screening test performed at one of the participating health centers during a baseline (2004–2005) or intervention period (2007–2008). Kaplan-Meier survival curves and proportional hazards regression examined the effect of patient navigation on time to definitive diagnosis, adjusting for covariates, clustering by clinic and differences between the baseline and intervention period.
We enrolled 997 subjects in the baseline period and 3,041 subjects during the intervention period, of whom 1,497 were in the navigated arm, and 1,544 in the control arm. There was a significant decrease in time to diagnosis for subjects in the navigated group compared with controls among those with a cervical screening abnormality (aHR 1.46, 95% CI: 1.1–1.9); and among those with a breast cancer screening abnormality who resolved after 60 days (aHR 1.40, 95% CI: 1.1–1.9), with no differences before 60 days.
This study documents a benefit of patient navigation on time to diagnosis among a racially/ethnically diverse inner city population.
Patient navigation may address cancer health disparities by reducing time to diagnosis following an abnormal cancer screening event.
PMCID: PMC3472624  PMID: 23045539
18.  Methadone Dose, Take Home Status and Hospital Admission among Methadone Maintenance Patients 
Journal of addiction medicine  2012;6(3):186-190.
Among patients receiving methadone maintenance treatment (MMT) for opioid dependence, receipt of unobserved dosing privileges (take homes) and adequate doses (i.e. ≥ 80mg) are each associated with improved addiction treatment outcomes, but the association with acute care hospitalization is unknown. We studied whether take-home dosing and adequate doses (i.e. ≥ 80 mg) were associated with decreased hospital admission among patients in a MMT program.
We reviewed daily electronic medical records of patients enrolled in one MMT program to determine receipt of take home doses, methadone dose ≥ 80mg and hospital admission date. Non-linear mixed effects logistic regression models were used to evaluate whether take home doses or dose ≥ 80mg on a given day were associated with hospital admission on the subsequent day. Covariates in adjusted models included age, gender, race/ethnicity, HIV status, medical illness, mental illness, and polysubstance use at program admission.
Subjects (n=138) had the following characteristics: mean age 43 years; 52% female; 17% HIV-infected; 32% medical illness; 40% mental illness; and 52% polysubstance use. During a mean follow-up of 20 months, 42 patients (30%) accounted for 80 hospitalizations. Receipt of take homes was associated with significantly lower odds of a hospital admission (AOR 0.26; 95%CI: 0.11-0.62), whereas methadone dose ≥ 80mg was not (AOR 1.01; 95% CI: 0.56-1.83).
Among MMT patients, receipt of take homes, but not dose of methadone, was associated with decreased hospital admission. Take home status may reflect not only patients’ improved addiction outcomes, but also reduced healthcare utilization.
PMCID: PMC3416958  PMID: 22694929
Methadone maintenance treatment; dose; take home status; hospital admission
19.  The Your Disease Risk Index for Colorectal Cancer Is an Inaccurate Risk Stratification Tool for Advanced Colorectal Neoplasia at Screening Colonoscopy 
Tailoring the use of screening colonoscopy based on the risk of advanced colorectal neoplasia (ACN) could optimize the cost-effectiveness of colorectal cancer (CRC) screening. Our goal was to assess the accuracy of the Your Disease Risk (YDR) CRC risk index for stratifying average risk patients into low- versus intermediate/high-risk categories for ACN. The YDR risk assessment tool was administered to 3,317 asymptomatic average risk patients 50 to 79 years of age just before their screening colonoscopy. Associations between YDR-derived relative risk (RR) scores and ACN prevalence were examined using logistic regression and χ2 analyses. ACN was defined as a tubular adenoma ≥1 cm, tubulovillous or villous adenoma of any size, and the presence of high-grade dysplasia or cancer. The overall prevalence of ACN was 5.6%. Although YDR-derived RR scores were linearly associated with ACN after adjusting for age and gender (P = 0.033), the index was unable to discriminate "below average" from "above/average" risk patients [OR, 1.01; 95% confidence interval (CI), 0.75–1.37]. Considerable overlap in rates of ACN was also observed between the different YDR risk categories in our age- and gender-stratified analyses. The YDR index lacks accuracy for stratifying average risk patients into low- versus intermediate/high-risk categories for ACN.
PMCID: PMC3632311  PMID: 22689913
20.  Effectiveness of a condensed protocol for disclosing APOE genotype and providing risk education for Alzheimer disease 
Brief, effective models of patient genetic education are needed for common, complex diseases. Using Alzheimer disease as a model, we compared participants’ risk knowledge and recall in extended versus condensed education protocols.
A four-site randomized clinical trial enrolled 280 first-degree relatives of individuals with Alzheimer disease (mean age = 58 years, 71% female); each received lifetime Alzheimer disease risk information (range: 13–74%) that incorporated apolipoprotein E genotype. In the condensed protocol, participants received an educational brochure in place of an in-person education session. Outcomes were assessed at 6 weeks and 6 months following risk disclosure.
The condensed protocol required less clinician time than the extended protocol (mean = 34 min vs. 77 min). The groups did not differ on recall of apolipoprotein E genotype or lifetime risk, and most participants in both groups recalled and retained this information over time. Both groups showed improvement from baseline in Alzheimer disease risk knowledge (e.g., understanding the magnitude of apolipoprotein E genotype effect on risk).
A condensed protocol for communicating genetic risk for Alzheimer disease achieved similar educational results as an extended protocol in this study. Further research should explore the efficacy of brief genetic education protocols for complex diseases in diverse populations.
PMCID: PMC3718049  PMID: 22498844
Alzheimer disease; APOE; genetic counseling; health education; risk communication
21.  Staging and Functional Characterization of Pheochromocytoma and Paraganglioma by 18F-Fluorodeoxyglucose (18F-FDG) Positron Emission Tomography 
Pheochromocytomas and paragangliomas (PPGLs) are rare tumors of the adrenal medulla and extra-adrenal sympathetic chromaffin tissues; their anatomical and functional imaging are critical to guiding treatment decisions. This study aimed to compare the sensitivity and specificity of 18F-fluorodeoxyglucose positron emission tomography with computed tomography (18F-FDG PET/CT) for tumor localization and staging of PPGLs with that of conventional imaging by [123I]-metaiodobenzylguanidine single photon emission CT (123I-MIBG SPECT), CT, and magnetic resonance imaging (MRI).
A total of 216 patients (106 men, 110 women, aged 45.2 ± 14.9 years) with suspected PPGL underwent CT or MRI, 18F-FDG PET/CT, and 123I-MIBG SPECT/CT. Sensitivity and specificity were measured as endpoints and compared by the McNemar test, using two-sided P values only.
Sixty (28%) of patients had nonmetastatic PPGL, 95 (44%) had metastatic PPGL, and 61 (28%) were PPGL negative. For nonmetastatic tumors, the sensitivity of 18F-FDG was similar to that of 123I-MIBG but less than that of CT/MRI (sensitivity of 18F-FDG = 76.8%; of 123I-MIBG = 75.0%; of CT/MRI = 95.7%; 18F-FDG vs 123I-MIBG: difference = 1.8%, 95% confidence interval [CI] = −14.8% to 14.8%, P = .210; 18F-FDG vs CT/MRI: difference = 18.9%, 95% CI = 9.4% to 28.3%, P < .001). The specificity was 90.2% for 18F-FDG, 91.8% for 123I-MIBG, and 90.2% for CT/MRI. 18F-FDG uptake was higher in succinate dehydrogenase complex– and von Hippel–Lindau syndrome–related tumors than in multiple endocrine neoplasia type 2 (MEN2) related tumors. For metastases, sensitivity was greater for 18F-FDG and CT/MRI than for 123I-MIBG (sensitivity of 18F-FDG = 82.5%; of 123I-MIBG = 50.0%; of CT/MRI = 74.4%; 18F-FDG vs 123I-MIBG: difference = 32.5%, 95% CI = 22.3% to 42.5%, P < .001; CT/MRI vs 123I-MIBG: difference = 24.4%, 95% CI = 11.3% to 31.6%, P < .001). For bone metastases, 18F-FDG was more sensitive than CT/MRI (sensitivity of 18F-FDG = 93.7%; of CT/MRI = 76.7%; difference = 17.0%, 95% CI = 4.9% to 28.5%, P = .013).
Compared with 123I-MIBG SPECT and CT/MRI, both considered gold standards for PPGL imaging, metastases were better detected by 18F-FDG PET. 18F-FDG PET provides a high specificity in patients with a biochemically established diagnosis of PPGL.
PMCID: PMC3341309  PMID: 22517990
22.  A Pharmacodynamic Study of the P-glycoprotein Antagonist CBT-1® in Combination With Paclitaxel in Solid Tumors 
The Oncologist  2012;17(4):512.
This pharmacodynamic trial evaluated the effect of CBT-1® on efflux by the ATP binding cassette (ABC) multidrug transporter P-glycoprotein (Pgp/MDR1/ABCB1) in normal human cells and tissues. CBT-1® is an orally administered bisbenzylisoquinoline Pgp inhibitor being evaluated clinically. Laboratory studies showed potent and durable inhibition of Pgp, and in phase I studies CBT-1® did not alter the pharmacokinetics of paclitaxel or doxorubicin.
CBT-1® was dosed at 500 mg/m2 for 7 days; a 3-hour infusion of paclitaxel at 135 mg/m2 was administered on day 6. Peripheral blood mononuclear cells (PBMCs) were obtained prior to CBT-1® administration and on day 6 prior to the paclitaxel infusion. 99mTc-sestamibi imaging was performed on the same schedule. The area under the concentration–time curve from 0–3 hours (AUC0–3) was determined for 99mTc-sestamibi.
Twelve patients were planned and enrolled. Toxicities were minimal and related to paclitaxel (grade 3 or 4 neutropenia in 18% of cycles). Rhodamine efflux from CD56+ PBMCs was a statistically significant 51%–100% lower (p < .0001) with CBT-1®. Among 10 patients who completed imaging, the 99mTc-sestamibi AUC0–3 for liver (normalized to the AUC0–3 of the heart) increased from 34.7% to 100.8% (median, 71.9%; p < .0001) after CBT-1® administration. Lung uptake was not changed.
CBT-1® is able to inhibit Pgp-mediated efflux from PBMCs and normal liver to a degree observed with Pgp inhibitors studied in earlier clinical trials. Combined with its ease of administration and lack of toxicity, the data showing inhibition of normal tissue Pgp support further studies with CBT-1® to evaluate its ability to modulate drug uptake in tumor tissue.
Although overexpression of ABCB1 and other ABC transporters has been linked with poor outcome following chemotherapy efforts to negate that through pharmacologic inhibition have generally failed. This is thought to be a result of several factors, including (a) failure to select patients with tumors in which ABCB1 is a dominant resistance mechanism; (b) inhibitors that were not potent, or that impaired drug clearance; and (c) the existence of other mechanisms of drug resistance, including other ABC transporters. Although an animal model for Pgp has been lacking, recent studies have exploited a Brca1−/−; p53−/− mouse model of hereditary breast cancer that develops sporadic tumors similar to cancers in women harboring BRCA1 mutations. Treatment with doxorubicin, docetaxel, or the poly(ADP-ribose) polymerase inhibitor olaparib brings about shrinkage, but resistance eventually emerges. Overexpression of the Abcb1a gene, the mouse ortholog of human ABCB1, has been shown to be a mechanism of resistance in a subset of these tumors. Treating mice with resistant tumors with olaparib plus the Pgp inhibitor tariquidar resensitized the tumors to olaparib. Although results in this animal model support a new look at Pgp as a target, in this era of “targeted therapies,” trial designs that directly assess modulation of drug uptake, including quantitative nuclear imaging, should be pursued before clinical efficacy assessments are undertaken. Such assessment should be performed with compounds that inhibit tissue Pgp without altering the pharmacokinetics of chemotherapeutic agents. This pharmacodynamic study demonstrated that CBT-1®, inhibits Pgp-mediated efflux from PBMCs and normal liver.
PMCID: PMC3336838  PMID: 22416063
23.  Willingness to Pay for Genetic Testing for Alzheimer's Disease: A Measure of Personal Utility 
Background: The increased availability of genetic tests for common, complex diseases, such as Alzheimer's disease (AD), raises questions about what people are willing to pay for these services. Methods: We studied willingness-to-pay for genetic testing in a study of AD risk assessment that included APOE genotype disclosure among 276 first-degree relatives of persons with AD. Results: Seventy-one percent reported that they would ask for such testing from their doctor if it were covered by health insurance, and 60% would ask for it even if it required self-pay. Forty-one percent were willing to pay more than $100 for testing, and more than half would have been willing to pay for the test out of pocket. Participants who learned that they were APOE ɛ4 positive and those who had higher education were less likely to want testing if covered by insurance, possibly to avoid discrimination. Conclusion: This is the first report to examine willingness to pay for susceptibility genetic testing in a sample of participants who had actually undergone such testing. These findings reveal that some participants find valuable personal utility in genetic risk information even when such information does not have proven clinical utility.
PMCID: PMC3241735  PMID: 21749214
24.  Reoperation for parathyroid adenoma: A contemporary experience 
Surgery  2009;146(6):1144-1155.
We reviewed reoperations for persistent or recurrent sporadic parathyroid adenoma to evaluate and compare our current results and outcomes to our previous experience.
From 1996 to 2008, 237 patients with persistent or recurrent hyperparathyroidism after failed operation underwent reoperation. Patients were re-explored with the assistance of non-invasive and sometimes invasive imaging.
A missed adenoma was suspected pre-operatively in 163 patients. Reoperation resulted in long-term resolution of hypercalcemia in 92%. Adenomas were in entopic locations in 32%; the most frequent ectopic location was the thymus (20%). Sestamibi scanning and ultrasonography were the most successful non-invasive imaging studies (96% positive predictive value (PPV) and 84% PPV respectively). Forty-four percent of patients had a reoperation based solely on non-invasive imaging. Of the invasive procedures performed, arteriography resulted in the best localization (92% PPV). Permanent recurrent laryngeal nerve injury occurred in 1.8%.
Compared to our prior experience (1982–1995), outcomes remained similar (92% resolution of hypercalcemia and 1.8% recurrent nerve injury currently versus 96% and 1.3% previously). Fewer patients received invasive studies for pre-operative localization (56% vs 73%, respectively). The decreased use of invasive imaging is due to technical improvements and greater confidence in the combination of ultrasonography and sestamibi scanning.
PMCID: PMC3467310  PMID: 19958942
25.  Tumor-induced osteomalacia 
Endocrine-related cancer  2011;18(3):R53-R77.
Tumor-induced osteomalacia (TIO) is a rare and fascinating paraneoplastic syndrome in which patients present with bone pain, fractures, and muscle weakness. The cause is high blood levels of the recently identified phosphate and vitamin D-regulating hormone, fibroblast growth factor 23 (FGF23). In TIO, FGF23 is secreted by mesenchymal tumors that are usually benign, but are typically very small and difficult to locate. FGF23 acts primarily at the renal tubule and impairs phosphate reabsorption and 1α-hydroxylation of 25-hydroxyvitamin D, leading to hypophosphatemia and low levels of 1,25-dihydroxy vitamin D. A step-wise approach utilizing functional imaging (F-18 fluorodeoxyglucose positron emission tomography and octreotide scintigraphy) followed by anatomical imaging (computed tomography and/or magnetic resonance imaging), and, if needed, selective venous sampling with measurement of FGF23 is usually successful in locating the tumors. For tumors that cannot be located, medical treatment with phosphate supplements and active vitamin D (calcitriol or alphacalcidiol) is usually successful; however, the medical regimen can be cumbersome and associated with complications. This review summarizes the current understanding of the pathophysiology of the disease and provides guidance in evaluating and treating these patients. Novel imaging modalities and medical treatments, which hold promise for the future, are also reviewed.
PMCID: PMC3433741  PMID: 21490240

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