Prospective evaluation of drug-drug interactions in ambulatory cancer patients initiated on prophylactic anticoagulation.

INTRODUCTION: Drug options for VTE prophylaxis are increasing for ambulatory cancer patients and data regarding anticoagulant-drug interactions and their relationship to VTE and bleeding are needed to improve care. METHODS: Over one year, 108 cancer patients with high VTE risk were prospectively identified. Potential anticoagulant-drug interactions were ascertained by chart review and graded on need for intervention. Providers selected anticoagulant prophylaxis based on potential drug interactions and patient-provider discussion. A cross-sectional analysis was performed thereafter to evaluate VTE and bleeding endpoints within one year of anticoagulant initiation. RESULTS: The average number of potential drug interactions per patient was higher for warfarin than others (3.04 vs. 1.28 (apixaban), 1.02 (rivaroxaban), and 0.98 (LMWH)). The severity of the interactions based on grade was, for apixaban: 1.6% grade X, 50.8% grade D, and 47.5% grade C; for rivaroxaban: 2.1% grade X, 64.9% grade D, 33.0% grade C; for LMWH, 0% grade X, 66.7% grade D, 33.3% grade C; and for warfarin, 0% grade X, 29.4% grade D, 70.6% grade C. At the end of the investigational period, 11 bleeds and 7 VTEs were reported. Drug combinations significantly associated with an increased bleeding risk were crizotinib with apixaban or rivaroxaban and PPIs with warfarin. The use of sulfamethoxazole-trimethoprim with warfarin was associated with an increased VTE risk. CONCLUSIONS: DOACs had fewer DDIs than warfarin, although interaction severity differed between anticoagulants. Some anticoagulant-drug interactions were associated with bleeding or VTE. Although not powered for analysis, DDI severity did not affect bleeding rates and inversely correlated with VTE risk.

Revisiting Prostate Cancer Screening Practices Among Vermont Primary Care Physicians.

The objective of this study was to assess the prostate cancer screening practices of Vermont primary care physicians and compare them with a prior study in 2001. An electronic survey was created and emailed to all currently practicing primary care physicians in Vermont. Data was stratified by practice length, practice location, university affiliation, and internal medicine versus family practice. Surveys were received from 123 (27.2%) primary care physicians. 27.7% of physicians in practice <10 years recommended prostate specific antigen (PSA) testing, compared with 55.9% of those practicing ≥10 years (p = 0.006). Of those who modified their recommendations in the past 5 years, 96.1% reported that the United States Preventive Services Task Force (USPSTF) 2012 statement influenced them. Respondents who continued to use PSA testing were less likely to stop screening after age 80 compared with those surveyed in 2001 (51% in 2014 vs. 74% in 2001; p <0.001). Primary care physicians in practice for 10 or more years were more likely to recommend PSA-based screening than those in practice for less time. The USPSTF statement discouraging PSA-based screening for prostate cancer has had significant penetrance among Vermont primary care physicians.

Phase II trial of subcutaneous methylnaltrexone in the treatment of severe opioid-induced constipation (OIC) in cancer patients: an exploratory study.

BACKGROUND: Methylnaltrexone is a peripherally acting mu-opioid receptor antagonist that has been shown to relieve severe opioid-induced constipation (OIC) in patients with advanced disease receiving palliative care. Its efficacy remains unknown in cancer patients who are not terminally ill. The primary aim of this study was to evaluate the efficacy of methylnaltrexone over 48 h in cancer patients who were not terminally ill. METHODS: In this single-dose phase II trial, cancer patients with a prognosis of ≥3 months and OIC with <3 laxations during the preceding week were eligible. The primary endpoint was a rescue-free laxation ≤4 h after a single dose of methylnaltrexone. Friedman's two-way analysis of variance was conducted for the number of laxations, pain and withdrawal scales, and laxation- and constipation-related symptoms. Univariate/bivariate Cox proportional hazard models for laxation times were employed. RESULTS: Twelve patients received methylnaltrexone. Eleven patients had an ECOG performance status of 1 or 2. Four (33.3 %) and 5 (41.7 %) patients had rescue-free laxation within 4 and 24 h, respectively, and 10 (83.3 %) had laxation within 48 h (p = 0.006). Difficulty passing a stool improved significantly over 48 h (p = 0.029). The bivariate Cox models revealed that a shorter time to laxation was associated with a higher baseline morphine equivalent daily dose (hazard ratio, 1.02 per 1 mg; p = 0.018) and a smaller number of laxations in the preceding week (hazard ratio, 0.13 per one laxation; p = 0.035). Patients tolerated methylnaltrexone well without opioid withdrawal. CONCLUSIONS: Methylnaltrexone may relieve severe OIC in cancer patients who are not terminally ill. A larger prospective study is justified in this population. (NCT01004393, https://clinicaltrials.gov/show/NCT01004393 ).

A Phase 1 Trial of TPI 287 as a Single Agent and in Combination With Temozolomide in Patients with Refractory or Recurrent Neuroblastoma or Medulloblastoma.

BACKGROUND: The primary aim of this Phase I study was to determine the maximum tolerated dose (MTD) of TPI 287 and the safety and tolerability of TPI 287 alone and in combination with temozolomide (TMZ) in pediatric patients with refractory or recurrent neuroblastoma or medulloblastoma. The secondary aims were to evaluate the pharmacokinetics of TPI 287 and the treatment responses. PROCEDURE: Eighteen patients were enrolled to a phase I dose escalation trial of weekly intravenous infusion of TPI 287 for two 28-day cycles with toxicity monitoring to determine the MTD, followed by two cycles of TPI 287 in combination with TMZ. Samples were collected to determine the pharmacokinetic parameters C(max), AUC(0-24), t(1/2), CL, and Vd on day 1 of cycles 1 (TPI 287 alone) and 3 (TPI 287 + TMZ) following TPI 287 infusion. Treatment response was evaluated by radiographic (CT or MRI) and radionuclide (MIBG) imaging for neuroblastoma. RESULTS: We determined the MTD of TPI 287 alone and in combination with temozolomide to be 125 mg/m(2). The non-dose-limiting toxicities at this dose were mainly anorexia and pain. The dose-limiting toxicities (DLTs) of two patients at 135 mg/m(2) were grade 3 hemorrhagic cystitis and grade 3 sensory neuropathy. CONCLUSIONS: Overall, TPI 287 was well tolerated by pediatric patients with refractory and relapsed neuroblastoma and medulloblastoma at a dose of 125 mg/m(2) IV on days 1, 8, and 15 of a 28 day cycle.

National Institutes of Health Pathways to Prevention Workshop: the role of opioids in the treatment of chronic pain.

This National Institutes of Health (NIH) Pathways to Prevention Workshop was cosponsored by the NIH Office of Disease Prevention (ODP), the NIH Pain Consortium, the National Institute on Drug Abuse, and the National Institute of Neurological Disorders and Stroke. A multidisciplinary working group developed the workshop agenda, and an evidence-based practice center prepared an evidence report through a contract with the Agency for Healthcare Research and Quality to facilitate the workshop discussion. During the 1.5-day workshop, invited experts discussed the body of evidence, and attendees had opportunities to provide comments during open discussion periods. After weighing evidence from the evidence report, expert presentations, and public comments, an unbiased, independent panel prepared a draft report that identified research gaps and future research priorities. The report was posted on the ODP Web site for 2 weeks for public comment. This article is an abridged version of the panel's full report, which is available at https://prevention.nih.gov/programs-events/pathways-to-prevention/workshops/opioids-chronic-pain/workshop-resources#final report.

Identification of tumor-binding scFv derived from clonally related B cells in tumor and lymph node of a patient with breast cancer.

The purpose of this study was to determine the clonal relationship between B cells within a breast cancer and the B cells in the tumor-draining lymph node (TDLN). We also determined the binding capacity of antibodies derived from these sources to autologous cancer and autologous noncancer breast tissue. Antibody clonality of B cells derived from tumor and lymph node was determined by analyzing heavy and light chain immunoglobulin sequences. The number of shared clonal groups observed between tumor and lymph node antibodies was significant for both heavy (p = 0.004) and light chain (p = 0.012) populations. Panning with phage-displayed single-chain variable fragment libraries derived from the tumor and lymph node B cells resulted in multiple antibodies that bound autologous tumor. Sequence analysis of enriched antibodies recovered after the third round of panning the tumor and TDLN libraries against autologous tumor lysates had a genetic relationship. These results indicate that B cells infiltrating a patient's breast cancer and B cells present in the tumor-draining lymph node are clonally and functionally related.

Effect of occult metastases on survival in node-negative breast cancer.

BACKGROUND: Retrospective and observational analyses suggest that occult lymph-node metastases are an important prognostic factor for disease recurrence or survival among patients with breast cancer. Prospective data on clinical outcomes from randomized trials according to sentinel-node involvement have been lacking. METHODS: We randomly assigned women with breast cancer to sentinel-lymph-node biopsy plus axillary dissection or sentinel-lymph-node biopsy alone. Paraffin-embedded tissue blocks of sentinel lymph nodes obtained from patients with pathologically negative sentinel lymph nodes were centrally evaluated for occult metastases deeper in the blocks. Both routine staining and immunohistochemical staining for cytokeratin were used at two widely spaced additional tissue levels. Treating physicians were unaware of the findings, which were not used for clinical treatment decisions. The initial evaluation at participating sites was designed to detect all macrometastases larger than 2 mm in the greatest dimension. RESULTS: Occult metastases were detected in 15.9% (95% confidence interval [CI], 14.7 to 17.1) of 3887 patients. Log-rank tests indicated a significant difference between patients in whom occult metastases were detected and those in whom no occult metastases were detected with respect to overall survival (P=0.03), disease-free survival (P=0.02), and distant-disease-free interval (P=0.04). The corresponding adjusted hazard ratios for death, any outcome event, and distant disease were 1.40 (95% CI, 1.05 to 1.86), 1.31 (95% CI, 1.07 to 1.60), and 1.30 (95% CI, 1.02 to 1.66), respectively. Five-year Kaplan-Meier estimates of overall survival among patients in whom occult metastases were detected and those without detectable metastases were 94.6% and 95.8%, respectively. CONCLUSIONS: Occult metastases were an independent prognostic variable in patients with sentinel nodes that were negative on initial examination; however, the magnitude of the difference in outcome at 5 years was small (1.2 percentage points). These data do not indicate a clinical benefit of additional evaluation, including immunohistochemical analysis, of initially negative sentinel nodes in patients with breast cancer. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT00003830.).

Threonyl-tRNA synthetase overexpression correlates with angiogenic markers and progression of human ovarian cancer.

BACKGROUND: Ovarian tumors create a dynamic microenvironment that promotes angiogenesis and reduces immune responses. Our research has revealed that threonyl-tRNA synthetase (TARS) has an extracellular angiogenic activity separate from its function in protein synthesis. The objective of this study was to test the hypothesis that TARS expression in clinical samples correlates with angiogenic markers and ovarian cancer progression. METHODS: Protein and mRNA databases were explored to correlate TARS expression with ovarian cancer. Serial sections of paraffin embedded ovarian tissues from 70 patients diagnosed with epithelial ovarian cancer and 12 control patients were assessed for expression of TARS, vascular endothelial growth factor (VEGF) and PECAM using immunohistochemistry. TARS secretion from SK-OV-3 human ovarian cancer cells was measured. Serum samples from 31 tissue-matched patients were analyzed by ELISA for TARS, CA-125, and tumor necrosis factor-α (TNF-α). RESULTS: There was a strong association between the tumor expression of TARS and advancing stage of epithelial ovarian cancer (p < 0.001). TARS expression and localization were also correlated with VEGF (p < 0.001). A significant proportion of samples included heavy TARS staining of infiltrating leukocytes which also correlated with stage (p = 0.017). TARS was secreted by ovarian cancer cells, and patient serum TARS was related to tumor TARS and angiogenic markers, but did not achieve significance with respect to stage. Multivariate Cox proportional hazard models revealed a surprising inverse relationship between TARS expression and mortality risk in late stage disease (p = 0.062). CONCLUSIONS: TARS expression is increased in epithelial ovarian cancer and correlates with markers of angiogenic progression. These findings and the association of TARS with disease survival provide clinical validation that TARS is associated with angiogenesis in ovarian cancer. These results encourage further study of TARS as a regulator of the tumor microenvironment and possible target for diagnosis and/or treatment in ovarian cancer.

Relationship between arm morbidity and patient-reported outcomes following surgery in women with node-negative breast cancer: NSABP protocol B-32.

BACKGROUND: The impact of arm morbidity following breast cancer surgery on patient-observed changes in daily functioning and health-related quality of life (HRQoL) has not been well-studied. OBJECTIVE: To examine the association of objective measures such as range of motion (ROM) and lymphedema, with patient-reported outcomes (PROs) in the arm and breast, upper extremity function, activities, and HRQoL. METHODS: The National Surgical Adjuvant Breast and Bowel Project Protocol B-32 was a randomized trial comparing sentinel node resection (SNR) with axillary dissection (AD) in women with node-negative breast cancer. ROM and arm volume were measured objectively. PROs included symptoms; arm function; limitations in social, recreational, occupational, and other regular activities; and a global index of HRQoL. Statistical methods included cross-tabulations and multivariable linear regression models. RESULTS: In all, 744 women provided at least 1 postsurgery assessment. About one-third of the patients experienced arm mobility restrictions. A similar number of patients avoided the use of the arm 6 months after surgery. Limitations in work and other regular activities were reported by about a quarter of the patients. In this multivariable analysis, arm mobility and sensory neuropathy were predictors of patient-reported arm function and overall HRQoL. Predictors for activity limitations also included side of surgery (dominant vs nondominant). Edema was not significant after adjustment for sensory neuropathy and ROM. LIMITATIONS: Arm mobility and edema were measured simultaneously only once during the follow-up (6 months). CONCLUSION: Clinical measures of sensory neuropathy and restrictions in arm mobility following breast cancer surgery are associated with self-reported limitations in activity and reductions in overall HRQoL.

In-advance end-of-life discussions and the quality of inpatient end-of-life care: a pilot study in bereaved primary caregivers of advanced cancer patients.

PURPOSE: Advanced cancer care planning is encouraged to achieve individualized care. We hypothesized that in-advance end-of-life (EOL) discussions and establishment of do-not-resuscitate (DNR) status prior to the terminal admission would be associated with better quality of inpatient EOL care. METHODS: We conducted a post-mortality survey, utilizing the validated Toolkit of Instruments to Measure End-of-Life Care. Primary caregivers (PCGs) of the advanced cancer patients who died at our institution between January 2009 and December 2010 were contacted more than 3 months after the patients' death. The endpoints included overall score for EOL care (0-10; 10 = best care), problem scores of six domains (0-1; 1 = worst problem), and score for supporting family's self-efficacy (knowing what to expect/do during the dying process) (1-3; 3 = greatest support). RESULTS: Of 115 PCGs contacted, 50 agreed to participate (43.5 %). Patients with EOL discussions (n = 20), as compared to those without (n = 29), had higher rating of overall EOL care (9.7 vs. 8.7; p = 0.001): lower problem scores in "informing and promoting shared decision-making" (0.121 vs. 0.239; p = 0.007), "encouraging advanced care planning" (0.033 vs. 0.167; p = 0.010), "focusing on individual" (0.051 vs. 0.186; p = 0.014), "attending to emotional/spiritual needs of family" (0.117 vs. 0.333; p = 0.010), and "providing care coordination" (0.100 vs. 0.198; p = 0.032), and greater support for family's self-efficacy (2.734 vs. 2.310; p < 0.001). No significant differences were found in these outcomes between patients with DNR (n = 19) and those with full code (n = 31) on admission. CONCLUSION: Advanced cancer patients may receive higher quality of inpatient EOL care if they had in-advance EOL discussions.

Ultrafast 3-T MRI in the evaluation of children with acute lower abdominal pain for the detection of appendicitis.

OBJECTIVE: The purpose of this study is to evaluate the feasibility of ultrafast 3-T MRI in the evaluation of children with acute lower abdominal pain for the detection of appendicitis. SUBJECTS AND METHODS: Forty-two pediatric patients (30 girls and 12 boys; mean age, 11.5 years; age range, 4-17 years) with acute abdominal pain were prospectively studied. Ultrafast 3-T MRI was performed with a three-plane single-shot turbo spin-echo sequence and an axial T2-weighted turbo spin-echo sequence with fat suppression. All scans were performed without sedation or oral or IV contrast agent. Scan times were less than 8 minutes 45 seconds (median, 5 minutes 40 seconds). Patients underwent CT or ultrasound or both as a comparison study to the MRI examination. The MRI, CT, and ultrasound examinations were interpreted independently by four board-certified radiologists who were blinded to patient information, study interpretations, surgical pathologic findings, and final diagnosis. RESULTS: Twelve of 42 cases of acute appendicitis were detected with 100% sensitivity, 99% specificity, 100% negative predictive value, and 98% positive predictive value, all of which were statistically significant (p < 0.01). The pooled and individual receiver operating characteristic curves for radiologists' interpretation of the diagnosis of acute appendicitis were greater than 0.95 in all cases (p < 0.01) CONCLUSION: Ultrafast 3-T MRI is a feasible alternative imaging modality for the diagnosis of acute appendicitis in children, particularly in cases where ultrasound is equivocal or nondiagnostic, as an alternative to CT. Ultrafast MRI requires no sedation and no oral or IV contrast agent and has no associated radiation exposure risks.

Pilot trial comparing COVID-19 publication database to conventional online search methods.

BACKGROUND AND OBJECTIVES: Literature review using search engines results in a list of manuscripts but does not provide the content contained in the manuscripts. Our goal was to evaluate user performance-based criteria of concept retrieval accuracy and efficiency using a new database system that contained information extracted from 1000 COVID-19 articles. METHODS: A sample of 17 students from the University of Vermont were randomly assigned to use the COVID-19 publication database or their usual preferred search methods to research eight prompts about COVID-19. The relevance and accuracy of the evidence found for each prompt were graded. A Cox proportional hazards' model with a sandwich estimator and Kaplan-Meier plots were used to analyse these data in a time-to-correct answer context. RESULTS: Our findings indicate that students using the new information management system answered significantly more prompts correctly and, in less time, than students using conventional research methods. Bivariate models for demographic factors indicated that previous research experience conferred an advantage in study performance, though it was found to be independent from the assigned research method. CONCLUSIONS: The results from this pilot randomised trial present a potential tool for more quickly and thoroughly navigating the literature on expansive topics such as COVID-19.

Sentinel-lymph-node resection compared with conventional axillary-lymph-node dissection in clinically node-negative patients with breast cancer: overall survival findings from the NSABP B-32 randomised phase 3 trial.

BACKGROUND: Sentinel-lymph-node (SLN) surgery was designed to minimise the side-effects of lymph-node surgery but still offer outcomes equivalent to axillary-lymph-node dissection (ALND). The aims of National Surgical Adjuvant Breast and Bowel Project (NSABP) trial B-32 were to establish whether SLN resection in patients with breast cancer achieves the same survival and regional control as ALND, but with fewer side-effects. METHODS: NSABP B-32 was a randomised controlled phase 3 trial done at 80 centres in Canada and the USA between May 1, 1999, and Feb 29, 2004. Women with invasive breast cancer were randomly assigned to either SLN resection plus ALND (group 1) or to SLN resection alone with ALND only if the SLNs were positive (group 2). Random assignment was done at the NSABP Biostatistical Center (Pittsburgh, PA, USA) with a biased coin minimisation approach in an allocation ratio of 1:1. Stratification variables were age at entry (≤ 49 years, ≥ 50 years), clinical tumour size (≤ 2·0 cm, 2·1-4·0 cm, ≥ 4·1 cm), and surgical plan (lumpectomy, mastectomy). SLN resection was done with a blue dye and radioactive tracer. Outcome analyses were done in patients who were assessed as having pathologically negative sentinel nodes and for whom follow-up data were available. The primary endpoint was overall survival. Analyses were done on an intention-to-treat basis. All deaths, irrespective of cause, were included. The mean time on study for the SLN-negative patients with follow-up information was 95·6 months (range 70·1-126·7). This study is registered with ClinicalTrials.gov, number NCT00003830. FINDINGS: 5611 women were randomly assigned to the treatment groups, 3989 had pathologically negative SLN. 309 deaths were reported in the 3986 SLN-negative patients with follow-up information: 140 of 1975 patients in group 1 and 169 of 2011 in group 2. Log-rank comparison of overall survival in groups 1 and 2 yielded an unadjusted hazard ratio (HR) of 1·20 (95% CI 0·96-1·50; p=0·12). 8-year Kaplan-Meier estimates for overall survival were 91·8% (95% CI 90·4-93·3) in group 1 and 90·3% (88·8-91·8) in group 2. Treatment comparisons for disease-free survival yielded an unadjusted HR of 1·05 (95% CI 0·90-1·22; p=0·54). 8-year Kaplan-Meier estimates for disease-free survival were 82·4% (80·5-84·4) in group 1 and 81·5% (79·6-83·4) in group 2. There were eight regional-node recurrences as first events in group 1 and 14 in group 2 (p=0·22). Patients are continuing follow-up for longer-term assessment of survival and regional control. The most common adverse events were allergic reactions, mostly related to the administration of the blue dye. INTERPRETATION: Overall survival, disease-free survival, and regional control were statistically equivalent between groups. When the SLN is negative, SLN surgery alone with no further ALND is an appropriate, safe, and effective therapy for breast cancer patients with clinically negative lymph nodes. FUNDING: US Public Health Service, National Cancer Institute, and Department of Health and Human Services.

Morbidity results from the NSABP B-32 trial comparing sentinel lymph node dissection versus axillary dissection.

BACKGROUND AND OBJECTIVES: Three year post-surgical morbidity levels were compared between patients with negative sentinel lymph node dissection alone (SLND) and those with negative sentinel node dissection and negative axillary lymph node dissection (ALND) in the NSABP B-32 trial. METHODS: A total of 1,975 ALND and 2,008 SLND node negative breast cancer patients had shoulder range of motion and arm volumes assessed along with self reports of arm tingling and numbness. Relative shoulder abduction deficits and relative arm volume differences between ipsilateral and contralateral arms were calculated. RESULTS: Shoulder abduction deficits >or=10% peaked at 1 week for the ALND (75%) and SLND (41%) groups. Arm volume differences >or=10% at 36 months were evident for the ALND (14%) and SLND (8%) groups. Numbness and tingling peaked at 6 months for the ALND (49%, 23%) and SLND (15%, 10%) groups. Logistic regression correlates of residual morbidity included treatment group, age, handedness, tumor size, systemic chemotherapy, and radiation to the axilla. CONCLUSIONS: Although residual morbidity for both treatment groups was evident, the results of the NSABP B-32 study indicate the superiority of the SLND compared to the ALND treatment approach relative to post-surgical morbidity outcomes over a 3-year follow-up period.

Internet delivered behavioral obesity treatment.

OBJECTIVES: To evaluate the efficacy of an Internet behavioral weight loss program; and determine if adding periodic in-person sessions to an Internet intervention improves outcomes. METHODS: 481 healthy overweight adults (28% minority) were randomized to one of 3 delivery methods of a behavioral weight loss program with weekly meetings: Internet (n=161), InPerson (n=158), or Hybrid (Internet+InPerson, n=162). Outcome variables were weight at baseline and 6 months and percent of subjects achieving a 5 and 7% weight loss. The study took place in two centers in Vermont and Arkansas from 2003 to 2008. RESULTS: Conditions differed significantly in mean weight loss [8.0 (6.1) kg vs. 5.5 (5.6) kg vs. 6.0 (5.5) kg], for InPerson, Internet, and Hybrid respectively, p<0.01, n=462). Weight loss for InPerson was significantly greater than the Internet and Hybrid conditions (p<0.05). Although the proportion reaching a 5% weight loss did not differ, the proportion losing 7% did differ significantly (56.3% vs. 37.3% vs. 44.4% for InPerson, Internet, and Hybrid respectively, p<0.01). CONCLUSIONS: These results demonstrate that the Internet is a viable alternative to in-person treatment for the delivery and dissemination of a behavioral weight-control intervention. The addition of periodic in-person sessions did not improve outcomes.

Primary care physicians' use of family history for cancer risk assessment.

BACKGROUND: Family history (FH) assessment is useful in identifying and managing patients at increased risk for cancer. This study assessed reported FH quality and associations with physician perceptions. METHODS: Primary care physicians practicing in two northeastern U.S. states were surveyed (n = 880; 70% response rate). Outcome measures of FH quality were extent of FH taken and ascertaining age at cancer diagnosis for affected family members. Predictors of quality measured in this survey included: perceived advantages and disadvantages of collecting FH information, knowledge of management options, access to supportive resources, and confidence in ability to interpret FH. RESULTS: Reported collection of information regarding second degree blood relatives and age of diagnosis among affected relatives was low. All hypothesized predictors were associated with measures of FH quality, but not all were consistent independent predictors. Perceived advantages of taking a family history, access to supportive resources, and confidence in ability to identify and manage higher risk patients were independent predictors of both FH quality measures. Perceived disadvantages of taking a family history was independently associated one measure of FH quality. Knowledge of management options was not independently associated with either quality measure. CONCLUSIONS: Modifiable perception and resource factors were independently associated with quality of FH taking in a large and diverse sample of primary care physicians. Improving FH quality for identification of high risk individuals will require multi-faceted interventions.

Intraoperative ultrasound versus mammographic needle localization for ductal carcinoma in situ.

BACKGROUND: Ductal carcinoma in situ (DCIS) often requires some method of localization to achieve breast-conserving therapy. The purpose of this study was to compare the efficacy of intraoperative ultrasound versus mammographic needle localization (MNL) for partial mastectomy in DCIS. MATERIALS AND METHODS: Data were collected from a Breast Cancer Surgery Database. All DCIS cases undergoing partial mastectomy (PM) were identified. Margin status, re-excision rates, and cost were determined for both groups. RESULTS: A total of 155 patients undergoing PM for DCIS were identified from the database. In the 96 patients undergoing ultrasound-guided PM (Group 1), the positive margin rate was 10.4%, and close margins (<1 mm) were observed in 22.9% after initial surgery. There were 59 patients who underwent MNL (Group 2); the positive margin rate was 11.9%, and close margins were observed in 27.1%. The difference between positive and close margins in Group 1 versus Group 2 was not statistically significant. The rate of re-excision was 20.8% for Group 1 and 30.5% for Group 2, resulting in 1.23 and 1.37 operations per patient, respectively. The average cost of an intraoperative ultrasound at our institution was $933 and $1858 for MNL (excluding cost of radiologic interpretation), a difference of $925 per case. CONCLUSION: Our study showed equivalent rates of positive margins and re-excision between intraoperative ultrasound and MNL when performing PM for nonpalpable DCIS. Considering the more invasive nature and increased cost of MNL, we consider surgeon-performed intraoperative ultrasound, when possible, the more cost-effective and practical procedure for patients with DCIS.

The impact of the interventionist-participant relationship on treatment adherence and weight loss.

Little is known about the impact of the relationship built between interventionists and their participants on weight loss. Our objective is to determine whether stronger early (i.e., 4 weeks) participant-interventionist bond is associated with significantly greater weight loss success and treatment adherence. Three hundred and ninety-eight participants received an online group behavioral weight control program over 18 months. Weight was measured objectively at baseline and at 6 and 18 months. At 4 weeks, participants completed the Working Alliance Inventory (WAI) bonding subscale, which measures the collaborative bond with the interventionist. Adherence (i.e., session attendance and online self-monitoring diary completion) was recorded by the interventionists. Participant-interventionist bond at 4 weeks was significantly associated with weight loss at 6 months (t(322) = -2.14, p = .03) but not at 18 months (t(290) = 0.53, p = .60). The model indicated that participant-interventionist bond at 4 weeks was a significant predictor of adherence at 6 months (b = .063, standard error [SE] = .30, p = .04), and 6 month adherence was a significant predictor of weight loss at 6 months (b = -.594, SE = .049, p < .0001). The indirect effect of the WAI-Bond subscale was significant (b = -.037, p = .03, 95% confidence interval: -.074, -.002) and accounted for 54% of the total effect of participant-interventionist bond on weight loss. However, the total weight loss explained by WAI-Bond subscale was small (0.04 kg). Participant-interventionist bond between participant and interventionist is an early predictor of treatment adherence and weight loss success at 6 months; however, the degree of weight loss explained by participant-interventionist bond is small and was not maintained at 18 months.

Internet-based weight control: the relationship between web features and weight loss.

Internet-based weight control programs have been showing promising results; however, as of yet, it is unclear which website components are critical for producing and maintaining weight loss. The aim of this study is to examine the utilization patterns of a weight control website and the relationship of the Web features to weight loss and maintenance. One hundred and twenty three (N = 123) participants took part in a 12-month behavioral weight control program over the Internet and their website utilization patterns were monitored. When examining the clustering of Web feature utilization and weight loss, the "feedback" factor (progress charts, physiological calculators, and past journals) was the best predictor of weight loss during the treatment period (baseline to 6 months), while the "social support" factor (Web chats and biographical information/e-mail addresses of participants) was the best predictor during maintenance. Weight loss in an online weight control program was related to dynamic Web features that provided feedback, support, and motivation to participants.

Acculturation and Perceptions of a Good Death Among Japanese Americans and Japanese Living in the U.S.

CONTEXT: Acculturation is the phenomenon of the attitudinal changes of individuals who come into continuous contact with another culture. Despite the long history of Japanese immigration to America, little is known about the impact of acculturation on perceptions of a good death. OBJECTIVES: To examine differences in perceptions of a good cancer death among Japanese Americans (JA/A), Japanese living in America (J/A), and the Japanese living in Japan (J/J). METHODS: We administered surveys among JA/A and J/A and used historical J/J data for reference. Primary endpoint was the proportion of respondents who expressed the necessity of core and optional items of the Good Death Inventory. Group differences ≥20% were deemed clinically important. RESULTS: In total, 441 survey responses in America and 2548 in Japan were obtained. More than 80% of respondents consistently considered nine of 10 core items necessary without significant group differences. No core item reached a ≥20% group difference. Three of the eight optional items reached ≥20% group difference: fighting against disease until one's last moment (49%, P < 0.0001; 52%, P < 0.0001; and 73% in JA/A, J/A, and J/J, respectively), knowing what to expect about one's condition in the future (83%, P < 0.0001; 80%, P < 0.0001; and 58%, respectively), and having faith (64%, P = 0.0548; 43%, P = 0.0127; and 38%, respectively). CONCLUSION: Although most core items of a good death were preserved throughout the levels of acculturation, perceptions of some optional items shifted away from Japanese attitudes as individuals became more acculturated. Understanding of different levels of acculturation may help clinicians provide culturally sensitive end-of-life care.