Recent Publications by CFE Educators

PURPOSE

To characterize demographic, disease, and cancer outcomes of men on active surveillance (AS) at a safety-net hospital and characterize those who were lost to follow-up (LTFU).

METHODS

From January 2004 to November 2014, 104 men with low-risk prostate cancer (PCa) were followed with AS at Zuckerberg San Francisco General Hospital (ZSFG). Criteria for AS have evolved over time; however, patients with diagnostic prostate-specific antigen (PSA) 10ng/mL or less, clinical stage T1/2, biopsy Gleason score 3 + 3 or 3 + 4, 33% or fewer positive cores, and 50% or less tumor in any single core were potentially eligible for AS. Men were longitudinally followed with a PSA or digital rectal examination or both every 3 to 6 months, and repeat prostate biopsy every 1 to 2 years. Clinical staging and grading were based on a physical examination and at least a 12-core biopsy, respectively. LTFU was defined as failure to successfully contact patients with 3 phone calls or any urology visit recorded within 18 months from a prior visit or biopsy. A secondary chart review was performed using the electronic medical record at ZSFG as well as EPIC Systems CareEverywhere which allows access to select non-ZSFG institutions to confirm that patients were truly LTFU.

RESULTS

Among the 104 men on AS at ZSFG, the median age at diagnosis of PCa was 61.5 years (range: 44-81). The median follow-up period was 29 months (range: 0-186 months) during which 18 (17.3%) men were LTFU and 48 (46%) remained on surveillance. Men underwent a median of 7 (1-21) serum PSA measurements and an average of 2 prostate biopsies (1-5). In total, 22 (20.6%) men had definitive treatment with the median time from diagnosis to active treatment being 26 (range: 2-87) months. Radiation therapy was more common than radical prostatectomy (12.5% vs. 7.7%). There was 1 PCa-related death and 3 noncancer deaths. Initial adherence to AS was poor; however, men committed to AS initially were ultimately more compliant over time.

CONCLUSION

AS for low-risk PCa is challenging among a vulnerable population receiving care in a safety-net hospital, as rates of LTFU were high. Our findings suggest the need for AS support programs to improve adherence and follow-up among vulnerable and underserved populations.

INTRODUCTION

The incidence of papillary thyroid cancer is increasing faster than any other cancer in young patients. The purpose of this review is to discuss the most recent determinants of risk of recurrence and compromised outcomes in this population. Areas covered: This review discusses the most updated data on patient age, including children and young adults, extent of disease and subsequent dynamic staging over time, molecular markers for disease aggressiveness, adequacy of surgical resection and surgeon volume, and novel therapies for advanced non-resectable disease as predictors of patient outcomes. Expert commentary: Young patients enjoy excellent outcomes, with long-term survivorship, but face higher risks of short-term complications and disease recurrence. Thoughtful evaluation of the extent of disease, tumor features associated with more aggressive behavior, the presence of locoregional or distant metastases, and an understanding of molecular changes in their tumors are important areas of consideration. High-volume surgeons should work collaboratively with endocrinologists, radiologists, and pathologists specializing in thyroid cancer to help patients achieve excellent outcomes. Emerging data challenging the status quo regarding the relative importance of patient age, tumor features, and dynamic risk-adjustment for overall prognosis of these patients will likely impact future care and staging systems.

BACKGROUND AND AIMS

Varying recommendations regarding the detection and management of dysplasia can lead to uncertainty and may impede the uptake of strategies that could improve surveillance in patients with inflammatory bowel disease (IBD). An educational event was held to assist in disseminating the recently published Surveillance for Colorectal Endoscopic Neoplasia Detection and Management in Inflammatory Bowel Disease Patients: International Consensus Recommendations (SCENIC).

METHODS

Specialists in IBD and endoscopy led the Optimizing Quality of Endoscopy in IBD course. The American Society for Gastrointestinal Endoscopy (ASGE) organized the course, and the Crohn's and Colitis Foundation of America (CCFA) provided endorsement. One was held in March 2015 at the ASGE Institute for Training and Technology in Chicago, Illinois, and the second in September 2016 preceding the ASGE Endofest in Chandler, Arizona. The program included interactive case-based discussions and didactic presentations on topics including the rationale and current approach of surveillance in IBD; endoscopic characterization and nomenclature of active and quiescent disease; detection of dysplasia during IBD surveillance; role of image-enhanced endoscopy in IBD surveillance, with a focus on chromoendoscopy technique; and management of dysplasia in IBD. Participants were surveyed before and after the course to assess their perspectives and practice.

RESULTS

Eighteen presenters or panel members and approximately 92 IBD and endoscopist physician leaders attended the meeting. Most attendees were aged 30 to 49 years (88.1%), had been in practice less than 10 years (89.7%), were from academic medical centers (90.7%), and spent >50% of their time caring for patients with IBD (59.7%). Recommended quality improvements for endoscopy in IBD included the use of endoscopic scoring systems to describe disease activity, the use of a modified Paris classification to characterize visible dysplastic lesions (polypoid, nonpolypoid with description of presence of ulcer and distinct or indistinct borders), the use of chromoendoscopy for dysplasia detection, and the endoscopic removal of visible dysplastic lesions. In the follow-up survey, participants were asked to indicate whether they had changed their practice as a result of attending the course. Ninety-three percent (93%) indicated they had changed their practice. For dysplasia detection, the use of chromoendoscopy increased: 51.7% of respondents reported using chromoendoscopy in most surveillance colonoscopies compared with 34.3% before the course. For dysplasia management, the use of EMR increased for polypoid and nonpolypoid lesions 10 to 20 mm in size; and the referral of dysplastic lesions 20 mm or larger that appeared endoscopically resectable shifted toward removal by an experienced endoscopist.

CONCLUSIONS

Evidence-based advances in endoscopy have occurred in the characterization and nomenclature of active and quiescent disease, polypoid and nonpolypoid dysplasia in IBD, and in the detection and management of dysplasia in colonic IBD. Implementation of updated guidelines and recommendations into clinical practice may be facilitated by interactive image- and video-based courses on the topic.

BACKGROUND

A low proportion of CD28CD8 T cells that express CD57 is associated with increased mortality in HIV infection. The effect of increasing body mass index (BMI) changes in the proportion of CD57CD28CD8 T cells among HIV-infected individuals on antiretroviral therapy is unknown.

SETTING

In a US cohort of HIV-infected women, we evaluated associations of BMI and waist circumference with 3 distinct CD8 T cell phenotypes: % CD28CD57CD8 T cells, % CD57 of CD28CD8 T cells, and % CD28 of all CD8 T cells.

METHODS

Multivariable linear regression analysis was used to estimate beta coefficients for each of 3 T-cell phenotypes. Covariates included HIV parameters (current and nadir CD4, current viral load), demographics (age, race, income, and study site), and lifestyle (tobacco and alcohol use) factors.

RESULTS

Of 225 participants, the median age was 46 years and 50% were obese (BMI >30 m/kg). Greater BMI and waist circumference were both associated with higher % CD28CD57CD8 T cells and % CD57 of all CD28CD8 T cells in multivariable analysis, including adjustment for HIV viral load (all P 0.05). The association between greater BMI and the overall proportion of CD28 CD8 cells in fully adjusted models (0.078, 95% confidence interval: -0.053 to 0.209) was not significant.

CONCLUSIONS

In this analysis, greater BMI and waist circumference are associated with greater expression of CD57 on CD28CD8 T cells and a greater proportion of CD57CD28 CD8 T cells. These findings may indicate that increasing BMI is immunologically protective in HIV-infected women. Future research is needed to understand the prognostic importance of these associations on clinical outcomes.

Importance

High-risk medical devices often undergo modifications, which are approved by the US Food and Drug Administration (FDA) through various kinds of premarket approval (PMA) supplements. There have been multiple high-profile recalls of devices approved as PMA supplements.

Objective

To characterize the quality of the clinical studies and data (strength of evidence) used to support FDA approval of panel-track supplements (a type of PMA supplement pathway that is used for significant changes in a device or indication for use and always requires clinical data).

Design and Setting

Descriptive study of clinical studies supporting panel-track supplements approved by the FDA between April 19, 2006, and October 9, 2015.

Exposure

Panel-track supplement approval.

Main Outcomes and Measures

Methodological quality of studies including randomization, blinding, type of controls, clinical vs surrogate primary end points, use of post hoc analyses, and reporting of age and sex.

Results

Eighty-three clinical studies supported the approval of 78 panel-track supplements, with 71 panel-track supplements (91%) supported by a single study. Of the 83 studies, 37 (45%) were randomized clinical trials and 25 (30%) were blinded. The median number of patients per study was 185 (interquartile range, 75-305), and the median follow-up duration was 180 days (interquartile range, 84-270 days). There were a total of 150 primary end points (mean [SD], 1.8 [1.2] per study), and 57 primary end points (38%) were compared with controls. Of primary end points with controls, 6 (11%) were retrospective controls and 51 (89%) were active controls. One hundred twenty-one primary end points (81%) were surrogate end points. Thirty-three studies (40%) did not report age and 25 (30%) did not report sex for all enrolled patients. The FDA required postapproval studies for 29 of 78 (37%) panel-track supplements.

Conclusions and Relevance

Among clinical studies used to support FDA approval of high-risk medical device modifications, fewer than half were randomized, blinded, or controlled, and most primary outcomes were based on surrogate end points. These findings suggest that the quality of studies and data evaluated to support approval by the FDA of modifications of high-risk devices should be improved.

BACKGROUND/OBJECTIVES

The P.A.L.Li.A.T.E. (prognostic assessment of life and limitations after trauma in the elderly) consortium has previously created a prognosis calculator for mortality after geriatric injury based on age, injury severity, and transfusion requirement called the geriatric trauma outcome score (GTOS). Here, we sought to create and validate a prognosis calculator called the geriatric trauma outcome score ii (GTOS II) estimating probability of unfavorable discharge.

DESIGN

Retrospective cohort.

SETTING

Four geographically diverse Level 1 trauma centers.

PARTICIPANTS

Trauma admissions aged 65 to 102 years surviving to discharge from 2000 to 2013.

INTERVENTION

None.

MEASUREMENTS

Age, injury severity score (ISS), transfusion at 24 hours post-admission, discharge dichotomized as favorable (home/rehabilitation) or unfavorable (skilled nursing/long term acute care/hospice). Training and testing samples were created using the holdout method. A multiple logistic mixed model (GTOS II) was created to estimate the odds of unfavorable disposition then re-specified using the GTOS II as the sole predictor in a logistic mixed model using the testing sample.

RESULTS

The final dataset was 16,114 subjects (unfavorable discharge status = 15.4%). Training (n = 8,057) and testing (n = 8,057) samples had similar demographics. The formula based on the training sample was (GTOS II = Age + [0.71 × ISS] + 8.79 [if transfused by 24 hours]). Misclassification rate and AUC were 15.63% and 0.67 for the training sample, respectively, and 15.85% and 0.67 for the testing sample.

CONCLUSION

GTOS II estimates the probability of unfavorable discharge in injured elders with moderate accuracy. With the GTOS mortality calculator, it can help in goal setting conversations after geriatric injury.

OBJECTIVE

To examine the association between distance traveled for an abortion and site of postabortion care among low-income women.

METHODS

We conducted a retrospective cohort study using claims data from 39,747 abortions covered by California's Medicaid program in 2011-2012. Primary outcomes were the odds of abortion-related visits to an emergency department (ED) and the original abortion site, and the secondary outcome was total abortion care costs. We used mixed-effects logistic regression adjusting for patient and abortion characteristics to examine the associations between distance traveled and subsequent abortion-related care at each location.

RESULTS

Among all abortions (N=39,747), 3% (95% CI 2.9-3.3, n=1,232) were followed by an ED visit (3% first-trimester aspirations, 2% second trimester or later, and 4% medication abortions) and 25% (95% CI 24.1-24.9, n=9,745) were followed by a visit to the original abortion site (4% first-trimester aspirations, 3% second-trimester or later, and 77% medication abortions). Women traveling farther for their abortions had higher odds of visiting an ED (100 or more miles compared with less than 25 miles, first-trimester aspirations: adjusted odds ratio [OR] 2.29, 95% CI 1.50-3.49; medication abortions: adjusted OR 2.30, 95% CI 1.34-3.93) and lower odds of returning to their abortion site for follow-up (100 or more miles compared with less than 25 miles, first-trimester aspirations: adjusted OR 0.36, 95% CI 0.18-0.70; second trimester or later: adjusted OR 0.52, 95% CI 0.31-0.88; and medication abortions: adjusted OR 0.33, 95% CI 0.23-0.50). Costs were consistently higher when subsequent care occurred at an ED rather than the abortion site (median cost $941 compared with $536, P.001).

CONCLUSION

For most patients, greater distance traveled for abortion was associated with increased likelihood of seeking subsequent care at an ED. Increasing the number of rural Medicaid abortion providers and reimbursing providers for telemedicine and alternatives to routine follow-up would likely improve continuity of care and reduce state costs by shifting the location of follow-up from EDs back to abortion providers.

BACKGROUND

There is a paucity of studies on transitions from IV insulin infusion (IVII) to subcutaneous (SC) insulin in the medical ICU (MICU).

METHODS

We conducted a retrospective study of patients admitted to the Cleveland Clinic MICU from June 2013 to January 2014 who received IVII. We compared blood glucose (BG) control between 3 cohorts based on timing of basal insulin dose: (1) NB (no basal), (2) IB (incorrect basal), (3) CB (correct basal) at 5 time points post-IVII discontinuation (1, 4, 8, 12, and 24h). Insulin doses used for transitioning were compared with 80% of estimated 24h IVII total. Analysis was done using chi-square, ANOVA and t-tests.

RESULTS

There were 269 patients (NB 166, IB 45, CB 58), 55% male with a mean age 58±16years. 103 patients (38%) had a transition attempted (IB 21%, CB 17%). The NB cohort had better BG than the IB cohort at all time points (p0.001) but also lower HbA1c, prior DM diagnosis and home insulin use (p0.001). IB and CB did not have significantly different BG with mean BG>180mg/dL at 4/5 time intervals. However, the dose of basal insulin used was less than 80% of estimated 24h IVII total (IB 21.4 vs 49.6U, CB 25vs 57.1U). Despite this, 15% of patients in the IB cohort and 24% of patients in the CB had hypoglycemic events.

CONCLUSION

The low rates of IV to SC insulin transitions raises the question of challenges to transitions.

PURPOSE

We sought to determine whether a behavioral weight reduction intervention would improve nonurinary incontinence lower urinary tract storage symptoms at 6 months, including urinary frequency, nocturia and urgency, compared to a structured education program serving as the control group among overweight and obese women with urinary incontinence.

MATERIALS AND METHODS

PRIDE (Program to Reduce Incontinence by Diet and Exercise) was a randomized clinical trial performed in 338 overweight or obese women with urinary incontinence. Participants were randomized, including 226 to 6-month behavioral weight loss intervention and 112 to the control group. All participants received a self-help behavioral treatment booklet to improve bladder control. On this secondary data analysis we examined changes in nonurinary incontinence lower urinary tract storage symptoms from baseline to 6 months and the impact of treatment allocation (intervention vs control), weight loss and physical activity.

RESULTS

Nonurinary incontinence lower urinary tract storage symptoms were common at baseline, varying from 48% to 62%. In the 2 groups combined women experienced significant improvement in nocturia, urgency and International Prostate Symptom Score at 6 months (all p 0.001). However, lower urinary tract storage symptom outcomes at 6 months did not differ between the intervention and control groups. Similarly no difference was observed in the amount of weight lost (5% or greater vs less than 5%) or physical activity (1,500 kcal or greater expenditure per week compared to less than 1,500 kcal).

CONCLUSIONS

Lower urinary tract storage symptoms were common among overweight and obese women with urinary incontinence. The prevalence decreased significantly after 6 months independent of treatment group assignment, amount of weight lost or physical activity. These improvements may have been due to self-help behavioral educational materials, trial participation or repeat assessment of symptoms.

Medulloblastoma is the most common malignant brain tumor affecting children. These tumors are high grade with propensity to metastasize within the central nervous system and, less frequently, outside the neuraxis. Recent advancements in molecular subgrouping of medulloblastoma refine diagnosis and improve counseling in regards to overall prognosis. Both are predicated on the molecular drivers of each subgroup-WNT-activated, SHH-activated, group 3, and group 4. The traditional therapeutic mainstay for medulloblastoma includes a multimodal approach with surgery, radiation, and multiagent chemotherapy. As we discover more about the molecular basis of medulloblastoma, efforts to adjust treatment approaches based on molecular risk stratification are under active investigation. Certainly, the known neurological, developmental, endocrine, and psychosocial injury related to medulloblastoma and its associated therapies motivate ongoing research towards improving treatment for this life-threatening tumor while at the same time minimizing long-term side effects.