Primary Care Practitioner Perceptions on the Follow-up of Abnormal Cancer Screening Test Results.

Importance: Health care systems focus on delivering routine cancer screening to eligible individuals, yet little is known about the perceptions of primary care practitioners (PCPs) about barriers to timely follow-up of abnormal results. Objective: To describe PCP perceptions about factors associated with the follow-up of abnormal breast, cervical, colorectal, and lung cancer screening test results. Design, Setting, and Participants: Survey study of PCPs from 3 primary care practice networks in New England between February and October 2020, prior to participating in a randomized clinical trial to improve follow-up of abnormal cancer screening test results. Participants were physicians and advanced practice clinicians from participating practices. Main Outcomes and Measures: Self-reported process, attitudes, knowledge, and satisfaction about the follow-up of abnormal cancer screening test results. Results: Overall, 275 (56.7%) PCPs completed the survey (range by site, 34.9%-71.9%) with more female PCPs (61.8% [170 of 275]) and general internists (73.1% [201 of 275]); overall, 28,7% (79 of 275) were aged 40 to 49 years. Most PCPs felt responsible for managing abnormal cancer screening test results with the specific cancer type being the best factor (range, 63.6% [175 of 275] for breast to 81.1% [223 of 275] for lung; P < .001). The PCPs reported limited support for following up on overdue abnormal cancer screening test results. Standard processes such as automated reports, reminder letters, or outreach workers were infrequently reported. Major barriers to follow-up of abnormal cancer screening test results across all cancer types included limited electronic health record tools (range, 28.5% [75 of 263]-36.5%[96 of 263]), whereas 50% of PCPs felt that there were major social barriers to receiving care for abnormal cancer screening test results for colorectal cancer. Fewer than half reported being very satisfied with the process of managing abnormal cancer screening test results, with satisfaction being greatest for breast cancer (46.9% [127 of 271]) and lowest for cervical (21.8% [59 of 271]) and lung cancer (22.4% [60 of 268]). Conclusions and Relevance: In this survey study of PCPs, important deficiencies in systems for managing abnormal cancer screening test results were reported. These findings suggest a need for comprehensive organ-agnostic systems to promote timely follow-up of abnormal cancer screening results using a primary care-focused approach across the range of cancer screening tests.

Natural Language Processing to Identify Abnormal Breast, Lung, and Cervical Cancer Screening Test Results from Unstructured Reports to Support Timely Follow-up.

Cancer screening and timely follow-up of abnormal results can reduce mortality. One barrier to follow-up is the failure to identify abnormal results. While EHRs have coded results for certain tests, cancer screening results are often stored in free-text reports, which limit capabilities for automated decision support. As part of the multilevel Follow-up of Cancer Screening (mFOCUS) trial, we developed and implemented a natural language processing (NLP) tool to assist with real-time detection of abnormal cancer screening test results (including mammograms, low-dose chest CT scans, and Pap smears) and identification of gynecological follow-up for higher risk abnormalities (i.e. colposcopy) from free-text reports. We demonstrate the integration and implementation of NLP, within the mFOCUS system, to improve the follow-up of abnormal cancer screening results in a large integrated healthcare system. The NLP pipelines have detected scenarios when guideline-recommended care was not delivered, in part because the provider mis-identified the text-based result reports.

Integrating tobacco treatment into lung cancer screening practices: Study protocol for the Screen ASSIST randomized clinical trial.

BACKGROUND: Integrating tobacco treatment services into lung cancer screening (LCS) has the potential to leverage a 'teachable moment' to promote cessation among long-term smokers and reduce disparities in tobacco treatment access. This protocol paper describes the Screen ASSIST (Aiding Screening Support In Stopping Tobacco) trial, which will identify how to best deliver evidence-driven tobacco treatment in the context of LCS. METHODS: Screen ASSIST is a randomized clinical trial with a 3-factor, fully crossed factorial design that enrolls current smokers (any cigarette use in the past 30 days) scheduled to attend LCS at multiple sites in the Mass General Brigham healthcare system. To maximize reach, recruitment is conducted at 3 time points: 1) at the time of LCS scheduling, 2) at the LCS visit, and 3) after the participant has received their LCS results. Participants are stratified by LCS study site and recruitment point and randomly assigned into 8 groups that test intervention components varying on telehealth counseling duration (4 weeks vs. 8 weeks), nicotine replacement therapy duration (2 weeks vs. 8 weeks), and systematic screening and referral for social determinants of health via a service named 'AuntBertha' (referral vs. no referral). The primary study outcome is self-reported past 7-day tobacco abstinence at 6-month follow-up. This trial will also assess systems integration and evaluate implementation of the intervention. DISCUSSION: Screen ASSIST will identify the most effective combination of tobacco cessation treatments within the LCS context, in order to improve the cost-effectiveness of LCS and quality of life among long-term heavy smokers.

Multilevel Follow-up of Cancer Screening (mFOCUS): Protocol for a multilevel intervention to improve the follow-up of abnormal cancer screening test results.

INTRODUCTION: While substantial attention is focused on the delivery of routine preventive cancer screening, less attention has been paid to systematically ensuring that there is timely follow-up of abnormal screening test results. Barriers to completion of timely follow-up occur at the patient, provider, care team and system levels. METHODS: In this pragmatic cluster randomized controlled trial, primary care sites in three networks are randomized to one of four arms: (1) standard care, (2) "visit-based" reminders that appear in a patient's electronic health record (EHR) when it is accessed by either patient or providers (3) visit based reminders with population health outreach, and (4) visit based reminders, population health outreach, and patient navigation with systematic screening and referral to address social barriers to care. Eligible patients in participating practices are those overdue for follow-up of an abnormal results on breast, cervical, colorectal and lung cancer screening tests. RESULTS: The primary outcome is whether an individual receives follow-up, specific to the organ type and screening abnormality, within 120 days of becoming eligible for the trial. Secondary outcomes assess the effect of intervention components on the patient and provider experience of obtaining follow-up care and the delivery of the intervention components. CONCLUSIONS: This trial will provide evidence for the role of a multilevel intervention on improving the follow-up of abnormal cancer screening test results. We will also specifically assess the relative impact of the components of the intervention, compared to standard care. TRIAL REGISTRATION: ClinicalTrials.gov NCT03979495.

Patient, provider, and clinic factors associated with the use of cervical cancer screening.

Cervical cancer screening delivery remains suboptimal. Understanding the multiple influences on use of screening is important to designing interventions. We describe the influence of patient, primary care provider (PCP), and clinic characteristics on whether a woman is up-to-date with cervical screening as of December 2016. PCPs (n = 194) and their female screen-eligible patients age 21-65 years (n = 32,115) were included in this cross-sectional analysis of patients from two primary care networks linked to a contemporaneous PCP survey. Principal independent variables for patients included: age, race, insurance, continuity of care; for PCP included: overall satisfaction with the practice of medicine, gender, hours worked per week, financial support for achieving clinical targets; and for clinic included: routine receipt of data on preventive care performance and language translation resources. Overall, 66.6% of women were up-to-date. Women were less likely to be up-to-date with cervical cancer screening if they were younger and were more likely to be screened if they were Black, Hispanic or Asian vs. White. Women with greater continuity of primary care or with a female PCP were more likely to be up-to-date (1.52; 1.33-1.75); those who received care in a clinic that was less prepared to manage language translation were less likely to be up-to-date (0.78; 0.65-0.95). Patient, provider, and clinic factors all influence use of cervical cancer screening. Systems interventions like improving continuity of care, promoting translation services, or enhanced efforts to track screening among patients of male PCPs may improve delivery.

Training as an Intervention to Decrease Medical Record Abstraction Errors Multicenter Studies.

Studies often rely on medical record abstraction as a major source of data. However, data quality from medical record abstraction has long been questioned. Electronic Health Records (EHRs) potentially add variability to the abstraction process due to the complexity of navigating and locating study data within these systems. We report training for and initial quality assessment of medical record abstraction for a clinical study conducted by the IDeA States Pediatric Clinical Trials Network (ISPCTN) and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Neonatal Research Network (NRN) using medical record abstraction as the primary data source. As part of overall quality assurance, study-specific training for medical record abstractors was developed and deployed during study start-up. The training consisted of a didactic session with an example case abstraction and an independent abstraction of two standardized cases. Sixty-nine site abstractors from thirty sites were trained. The training was designed to achieve an error rate for each abstractor of no greater than 4.93% with a mean of 2.53%, at study initiation. Twenty-three percent of the trainees exceeded the acceptance limit on one or both of the training test cases, supporting the need for such training. We describe lessons learned in the design and operationalization of the study-specific, medical record abstraction training program.

Randomized Trial of Personalized Breast Density and Breast Cancer Risk Notification.

BACKGROUND: Despite widespread implementation of mammographic breast density (MBD) notification laws, the impact of these laws on knowledge of MBD and knowledge of breast cancer risk is limited by the lack of tools to promote informed decision-making in practice. OBJECTIVE: To develop and evaluate whether brief, personalized informational videos following a normal mammogram in addition to a legislatively required letter about MBD result can improve knowledge of MBD and breast cancer risk compared to standard care (i.e., legislatively required letter about MBD included with the mammogram result). DESIGN/PARTICIPANTS: Prospective randomized controlled trial of English-speaking women, age 40-74 years, without prior history of breast cancer, receiving a screening mammogram with a normal or benign finding (intervention group n = 235, control group n = 224). INTERVENTION: brief (3-5 min) video, personalized to a woman's MBD result and breast cancer risk. MAIN MEASURES: Primary outcomes were a woman's knowledge of her MBD and risk of breast cancer. Secondary outcomes included whether a woman reported that she discussed the results of her mammogram with her primary care provider (PCP). KEY RESULTS: Relative to women in the control arm, women in the intervention arm had greater improvement in their knowledge of both their personal MBD (intervention pre/post 39.2%/ 77.5%; control pre/post 36.2%/ 37.5%; odds ratio (OR) 5.34 for change for intervention vs. control, 95% confidence interval (CI) 3.87-7.36; p < 0.001) and risk of breast cancer (intervention pre/post: 66.8%/74.0%; control pre/post 67.9%/ 65.2%; OR 1.42, 95% confidence interval (CI) 1.09-1.84; p = 0.01). Women in the intervention group were more likely than those in the control group to report discussing the results of their mammogram with their PCP (p = 0.05). CONCLUSIONS: Brief, personalized videos following mammography can improve knowledge of MBD and personal risk of breast cancer compared to a legislatively mandated informational letter. Trial Registration Clinicaltrials.gov (NCT02986360).

Multi-level Influences on Breast Cancer Screening in Primary Care.

BACKGROUND: Use of breast cancer screening is influenced by factors associated with patients, primary care providers, practices, and health systems. OBJECTIVE: We examined the relative effects of these nested levels on four breast cancer screening metrics. DESIGN: A web-based survey was completed at 15 primary care practices within two health systems representing 306 primary care providers (PCPs) serving 46,944 women with a primary care visit between 1/2011-9/2014. Analyses occurred between 1/2017 and 5/2017. MAIN MEASURES: Across four nested levels (patient, PCP, primary care practice, and health system), frequency distributions and adjusted rates of primary care practice characteristics and survey results for four breast screening metrics (percent screened overall, and percent screened age 40-49, 50-74, and 75+) were reported. We used hierarchical multi-level mixed and random effects analysis to assess the relative influences of PCP, primary care practice, and health system on the breast screening metrics. KEY RESULTS: Overall, the proportion of women undergoing breast cancer screening was 73.1% (73.4% for ages 40-49, 76.5% for 50-74, and 51.1% for 75+). Patient ethnicity and number of primary care visits were strongly associated with screening rates. After adjusting for woman-level factors, 24% of the overall variation among PCPs was attributable to the primary care practice level, 35% to the health system level, and 41% to the residual variation among PCPs within practice. No specific provider-level characteristics were found to be statistically significant determinants of screening rates. CONCLUSIONS: After accounting for woman-level characteristics, the remaining variation in breast cancer screening was largely due to provider and health system variation.

Issues with analyzing noble gases using gas chromatography with thermal conductivity detection.

The noble gases, namely neon, argon, krypton and xenon, have many uses including in incandescent and gas discharge lighting, in plasma televisions, shielding gas in welding, in lasers for surgery and semiconductors, and in magnetic resonance imaging (MRI) of the lungs. When incorporating these noble gases in industries, especially the medical field, it is important to know accurately the composition of the noble gas mixture. Therefore, there is a need for accurate gas standards that can be used to determine the noble gas amount-of-substance fraction in the appropriate mixture application. A recent comparison of mixtures containing four noble gases in a helium balance showed mixed results among National Metrology Institutes. Significant differences, 0.7 to 3.8% relative, were seen in the analytical amount-of-substance assignments versus the gravimetric value of the noble gases in the comparison mixture when using "binary standards", i.e. neon in helium, argon in helium and krypton in helium, as applied by the National Institute of Standards and Technology. Post-comparison studies showed that when all four noble gases were included in the standards, the agreement between analytical and gravimetric values was within 0.05% relative. Further research revealed that different carrier gases (hydrogen, helium and nitrogen) resulted in varying differences between the analytical and gravimetric values assignments. This paper will discuss the findings of these analytical comparisons. Graphical abstract ᅟ.

Diffusion of digital breast tomosynthesis among women in primary care: associations with insurance type.

Digital breast tomosynthesis (DBT) has shown potential to improve breast cancer screening and diagnosis compared to digital mammography (DM). The FDA approved DBT use in conjunction with conventional DM in 2011, but coverage was approved by CMS recently in 2015. Given changes in coverage policies, it is important to monitor diffusion of DBT by insurance type. This study examined DBT trends and estimated associations with insurance type. From June 2011 to September 2014, DBT use in 22 primary care centers in the Dartmouth -Brigham and Women's Hospital Population-based Research Optimizing Screening through Personalized Regimens research center (PROSPR) was examined among women aged 40-89. A longitudinal repeated measures analysis estimated the proportion of DBT performed for screening or diagnostic indications over time and by insurance type. During the study period, 93,182 mammograms were performed on 48,234 women. Of these exams, 16,506 DBT tests were performed for screening (18.1%) and 2537 were performed for diagnosis (15.7%). Between 2011 and 2014, DBT utilization increased in all insurance groups. However, by the latest observed period, screening DBT was used more frequently under private insurance (43.4%) than Medicaid (36.2%), Medicare (37.8%), other (38.6%), or no insurance (32.9%; P < 0.0001). No sustained differences in use of DBT for diagnostic testing were seen by insurance type. DBT is increasingly used for breast cancer screening and diagnosis. Use of screening DBT may be associated with insurance type. Surveillance is required to ensure that disparities in breast cancer screening are minimized as DBT becomes more widely available.

Alignment of breast cancer screening guidelines, accountability metrics, and practice patterns.

OBJECTIVES: Breast cancer screening guidelines and metrics are inconsistent with each other and may differ from breast screening practice patterns in primary care. This study measured breast cancer screening practice patterns in relation to common evidence-based guidelines and accountability metrics. STUDY DESIGN: Cohort study using primary data collected from a regional breast cancer screening research network between 2011 and 2014. METHODS: Using information on women aged 30 to 89 years within 21 primary care practices of 2 large integrated health systems in New England, we measured the proportion of women screened overall and by age using 2 screening definition categories: any mammogram and screening mammogram. RESULTS: Of the 81,352 women in our cohort, 54,903 (67.5%) had at least 1 mammogram during the time period, 48,314 (59.4%) had a screening mammogram. Women aged 50 to 69 years were the highest proportion screened (82.4% any mammogram, 75% screening indication); 72.6% of women at age 40 had a screening mammogram with a median of 70% (range = 54.3%-84.8%) among the practices. Of women aged at least 75 years, 63.3% had a screening mammogram, with the median of 63.9% (range = 37.2%-78.3%) among the practices. Of women who had 2 or more mammograms, 79.5% were screened annually. CONCLUSIONS: Primary care practice patterns for breast cancer screening are not well aligned with some evidence-based guidelines and accountability metrics. Metrics and incentives should be designed with more uniformity and should also include shared decision making when the evidence does not clearly support one single conclusion.

Primary Care Providers' Beliefs and Recommendations and Use of Screening Mammography by their Patients.

BACKGROUND: Revised breast cancer screening guidelines have fueled debate about the effectiveness and frequency of screening mammography, encouraging discussion between women and their providers. OBJECTIVE: To examine whether primary care providers' (PCPs') beliefs about the effectiveness and frequency of screening mammography are associated with utilization by their patients. DESIGN: Cross-sectional survey data from PCPs (2014) from three primary care networks affiliated with the Population-based Research Optimizing Screening through Personalized Regimens (PROSPR) consortium, linked with data about their patients' mammography use (2011-2014). PARTICIPANTS: PCPs (n = 209) and their female patients age 40-89 years without breast cancer (n = 30,233). MAIN MEASURES: Outcomes included whether (1) women received a screening mammogram during a 2-year period; and (2) screened women had >1 mammogram during that period, reflecting annual screening. Principal independent variables were PCP beliefs about the effectiveness of mammography and their recommendations for screening frequency. KEY RESULTS: Overall 65.2% of women received >1 screening mammogram. For women 40-48 years, mammography use was modestly lower for those cared for by PCPs who believed that screening was ineffective compared with those who believed it was somewhat or very effective (59.1%, 62.3%, and 64.7%; p = 0.019 after controlling for patient characteristics). Of women with PCPs who reported they did not recommend screening before age 50, 48.1% were nonetheless screened. For women age 49-74 years, the vast majority were cared for by providers who believed that screening was effective. Provider recommendations were not associated with screening frequency. For women ≥75 years, those cared for by providers who were uncertain about effectiveness had higher screening use (50.7%) than those cared for by providers who believed it was somewhat effective (42.8%). Patients of providers who did not recommend screening were less likely to be screened than were those whose providers recommended annual screening, yet 37.1% of patients whose providers recommended against screening still received screening. CONCLUSIONS: PCP beliefs about mammography effectiveness and screening recommendations are only modestly associated with use, suggesting other likely influences on patient participation in mammography.

Challenges With Identifying Indication for Examination in Breast Imaging as a Key Clinical Attribute in Practice, Research, and Policy.

PURPOSE: To assess indication for examination for four breast imaging modalities and describe the complexity and heterogeneity of data sources and ascertainment methods. METHODS: Indication was evaluated among the Population-based Research Optimizing Screening through Personalized Regimens (PROSPR) breast cancer research centers (PRCs). Indication data were reported overall and separately for four breast imaging modalities: digital mammography (DM), digital breast tomosynthesis (DBT), ultrasound (US), and magnetic resonance imaging (MRI). RESULTS: The breast PRCs contributed 236,262 women with 607,735 breast imaging records from 31 radiology facilities. We found a high degree of heterogeneity for indication within and across six data sources. Structured codes within a data source were used most often to identify indication for mammography (59% DM, 85% DBT) and text analytics for US (45%) and MRI (44%). Indication could not be identified for 17% of US and 26% of MRI compared with 2% of mammography examinations (1% DM, 3% DBT). CONCLUSIONS: Multiple and diverse data sources, heterogeneity of ascertainment methods, and nonstandardization of codes within and across data systems for determining indication were found. Consideration of data sources and standardized methodology for determining indication is needed to assure accurate measurement of cancer screening rates and performance in clinical practice and research.

Assessing Inaccuracies in Automated Information Extraction of Breast Imaging Findings.

We previously identified breast imaging findings from radiology reports using an expert-based information extraction algorithm as part of the National Cancer Institute's Population-based Research Optimizing Screening through Personalized Regimens (PROSPR) initiative. We validate this algorithm and assess inaccuracies in a different institutional setting. Mammography, ultrasound (US), and breast magnetic resonance imaging (MRI) reports of patients at an academic health system between 4/2013 and 6/2013 were included for analysis. Accuracy of automatically extracting imaging findings using an algorithm developed at a different institution compared to manual gold standard review is reported. Extraction errors are further categorized based on manual review. Precision and recall for extracting BI-RADS categories remain between 0.9 and 1.0, except for MRI (0.7). F measures for extracting other findings are 0.9 for non-mass enhancement (in MRI) and 0.8-0.9 for cysts (in MRI and US). Extracting breast imaging findings resulted in lowest accuracy for findings of calcification (range 0.4-0.6 in mammography) and asymmetric density (0.5-0.7 in mammography). Majority of errors for extracting imaging findings were due to qualifier-based errors, descriptors which indicate absence of findings, missed by automated extraction (e.g., "benign" calcifications). Our information extraction algorithm provides an effective approach to extracting some breast imaging findings for populating a breast screening registry. However, errors in information extraction when utilizing methods in new settings demonstrate that further work is necessary to extract information content from unstructured multi-institutional radiology reports.

Inadequate Systems to Support Breast and Cervical Cancer Screening in Primary Care Practice.

BACKGROUND: Despite substantial resources devoted to cancer screening nationally, the availability of clinical practice-based systems to support screening guidelines is not known. OBJECTIVE: To characterize the prevalence and correlates of practice-based systems to support breast and cervical cancer screening, with a focus on the patient-centered medical home (PCMH). DESIGN: Web and mail survey of primary care providers conducted in 2014. The survey assessed provider (gender, training) and facility (size, specialty training, physician report of National Committee for Quality Assurance (NCQA) PCMH recognition, and practice affiliation) characteristics. A hierarchical multivariate analysis clustered by clinical practice was conducted to evaluate characteristics associated with the adoption of practice-based systems and technology to support guideline-adherent screening. PARTICIPANTS: Primary care physicians in family medicine, general internal medicine, and obstetrics and gynecology, and nurse practitioners or physician assistants from four clinical care networks affiliated with PROSPR (Population-based Research Optimizing Screening through Personalized Regimens) consortium research centers. MAIN MEASURES: The prevalence of routine breast cancer risk assessment, electronic health record (EHR) decision support, comparative performance reports, and panel reports of patients due for routine screening and follow-up. KEY RESULTS: There were 385 participants (57.6 % of eligible). Forty-seven percent (47.0 %) of providers reported NCQA recognition as a PCMH. Less than half reported EHR decision support for breast (48.8 %) or cervical cancer (46.2 %) screening. A minority received comparative performance reports for breast (26.2 %) or cervical (19.7 %) cancer screening, automated reports of patients overdue for breast (18.7 %) or cervical (16.4 %) cancer screening, or follow-up of abnormal breast (18.1 %) or cervical (17.6 %) cancer screening tests. In multivariate analysis, reported NCQA recognition as a PCMH was associated with greater use of comparative performance reports of guideline-adherent breast (OR 3.23, 95 % CI 1.58-6.61) or cervical (OR 2.56, 95 % CI 1.32-4.96) cancer screening and automated reports of patients overdue for breast (OR 2.19, 95 % CI 1.15-41.7) or cervical (OR. 2.56, 95 % CI 1.26-5.26) cancer screening. CONCLUSIONS: Providers lack systems to support breast and cervical cancer screening. Practice transformation toward a PCMH may support the adoption of systems to achieve guideline-adherent cancer screening in primary care settings.

Hearing the Community: Evolution of a Nutrition and Physical Activity Program for African American Women to Improve Weight.

Listening to the needs of the community is an important step toward reducing health disparities. Researchers may need to adjust their methods to maximize participation and benefit to the community. This report describes how the project team adjusted its approach to a weight loss intervention to support a community of African American women seeking to improve their health.

Take the money and run? Redemption of a gift card incentive in a clinician survey.

BACKGROUND: Clinician surveys provide critical information about many facets of health care, but are often challenging to implement. Our objective was to assess use by participants and non-participants of a prepaid gift card incentive that could be later reclaimed by the researchers if unused. METHODS: Clinicians were recruited to participate in a mailed or online survey as part of a study to characterize women's primary health care provider attitudes towards breast and cervical cancer screening guidelines and practices (n = 177). An up-front incentive of a $50 gift card to a popular online retailer was included with the study invitation. Clinicians were informed that the gift card would expire if it went unused after 4 months. Outcome measures included use of gift cards by participants and non-participants and comparison of hypothetical costs of different incentive strategies. RESULTS: 63.5% of clinicians who responded to the survey used the gift card, and only one provider who didn't participate used the gift card (1.6%). Many of those who participated did not redeem their gift cards (36.5% of respondents). The price of the incentives actually claimed totaled $3700, which was less than half of the initial outlay. Since some of the respondents did not redeem their gift cards, the cost of incentives was less than it might have been if we had provided a conditional incentive of $50 to responders after they had completed the survey. CONCLUSIONS: Redeemable online gift card codes may provide an effective way to motivate clinicians to participate in surveys.

Patients with Refractory Crohn's Disease Successfully Treated with Ustekinumab.

BACKGROUND: Ustekinumab is a new biologic therapy targeting interleukin-12 and interleukin -23. It is currently approved for the treatment of psoriasis, but clinical trials have shown that it can induce and maintain remission in Crohn's disease (CD). We aim to evaluate effectiveness of ustekinumab in the treatment of CD. METHODS: A retrospective chart review was performed including patients (pts) from 2 academic medical centers with complicated, refractory CD started on ustekinumab between June 2011 and June 2014. Pts were treated based on a novel subcutaneous dosing schedule designed to simulate the intravenous load used in clinical trials. RESULTS: Forty-five pts were treated with ustekinumab during this study period. Of the pts who had clinical parameters available before and after medication start, 46% achieved clinical response (Harvey-Bradshaw index decrease ≥ 3) and 35% achieved clinical remission (Harvey-Bradshaw index ≤ 3). Short inflammatory bowel disease questionnaire scores increased significantly (46 [20, 68] to 55 [32, 70], P < 0.05). Erythrocyte sedimentation rate decreased significantly (20 [3, 54] to 12 [0, 42] mm/h, P < 0.05). C-reactive protein decreased significantly (4.9 [0.3, 111] to 3.3 [0.2, 226] mg/L, P < 0.05). Seventy-six percent of patients demonstrated an endoscopic response and 24% achieved complete endoscopic remission. Twelve patients (26%) were hospitalized for IBD-related issues. Four pts had infection-related complications. Six pts (13%) underwent surgery for IBD-related issues. Three pts stopped ustekinumab, 1 for pt preference and 2 for the lack of response. CONCLUSIONS: Using a novel subcutaneous dosing schedule, ustekinumab was successful in improving clinical, laboratory, and endoscopic markers of disease activity in patients with severe, refractory CD.

Provider Attitudes and Screening Practices Following Changes in Breast and Cervical Cancer Screening Guidelines.

BACKGROUND: Changes to national guidelines for breast and cervical cancer screening have created confusion and controversy for women and their primary care providers. OBJECTIVE: To characterize women's primary health care provider attitudes towards screening and changes in practice in response to recent revisions in guidelines for breast and cervical cancer screening. DESIGN, SETTING, PARTICIPANTS: In 2014, we distributed a confidential web and mail survey to 668 women's health care providers affiliated with the four clinical care networks participating in the three PROSPR (Population-based Research Optimizing Screening through Personalized Regimens) consortium breast cancer research centers (385 respondents; response rate 57.6 %). MAIN MEASURES: We assessed self-reported attitudes toward breast and cervical cancer screening, as well as practice changes in response to the most recent revisions of the U.S. Preventive Services Task Force (USPSTF) recommendations. KEY RESULTS: The majority of providers believed that mammography screening was effective for reducing cancer mortality among women ages 40-74 years, and that Papanicolaou (Pap) testing was very effective for women ages 21-64 years. While the USPSTF breast and cervical cancer screening recommendations were widely perceived by the respondents as influential, 75.7 and 41.2 % of providers (for mammography and cervical cancer screening, respectively) reported screening practices in excess of those recommended by USPSTF. Provider-reported barriers to concordance with guideline recommendations included: patient concerns (74 and 36 % for breast and cervical, respectively), provider disagreement with the recommendations (50 and 14 %), health system measurement of a provider's screening practices that use conflicting measurement criteria (40 and 21 %), concern about malpractice risk (33 and 11 %), and lack of time to discuss the benefits and harms with their patients (17 and 8 %). CONCLUSIONS: Primary care providers do not consistently follow recent USPSTF breast and cervical cancer screening recommendations, despite noting that these guidelines are influential.

NMR-based Structural Analysis of Threonylcarbamoyl-AMP Synthase and Its Substrate Interactions.

The hypermodified nucleoside N(6)-threonylcarbamoyladenosine (t(6)A37) is present in many distinct tRNA species and has been found in organisms in all domains of life. This post-transcriptional modification enhances translation fidelity by stabilizing the anticodon/codon interaction in the ribosomal decoding site. The biosynthetic pathway of t(6)A37 is complex and not well understood. In bacteria, the following four proteins have been discovered to be both required and sufficient for t(6)A37 modification: TsaC, TsaD, TsaB, and TsaE. Of these, TsaC and TsaD are members of universally conserved protein families. Although TsaC has been shown to catalyze the formation of L-threonylcarbamoyl-AMP, a key intermediate in the biosynthesis of t(6)A37, the details of the enzymatic mechanism remain unsolved. Therefore, the solution structure of Escherichia coli TsaC was characterized by NMR to further study the interactions with ATP and L-threonine, both substrates of TsaC in the biosynthesis of L-threonylcarbamoyl-AMP. Several conserved amino acids were identified that create a hydrophobic binding pocket for the adenine of ATP. Additionally, two residues were found to interact with L-threonine. Both binding sites are located in a deep cavity at the center of the protein. Models derived from the NMR data and molecular modeling reveal several sites with considerable conformational flexibility in TsaC that may be important for L-threonine recognition, ATP activation, and/or protein/protein interactions. These observations further the understanding of the enzymatic reaction catalyzed by TsaC, a threonylcarbamoyl-AMP synthase, and provide structure-based insight into the mechanism of t(6)A37 biosynthesis.