Recent Publications by CFE Educators

PURPOSE

To characterize the effect of palliative care provided concurrently with usual urologic care for patients with bladder cancer undergoing cystectomy.

MATERIALS AND METHODS

Prospective, 6-month, serial cohort study comparing 33 participants receiving usual care with cystectomy for muscle-invasive bladder cancer, with 30 participants also receiving concurrent palliative care. Patients and family caregivers completed validated symptom assessment and satisfaction surveys preoperatively and at 2, 4, and 6 months postoperatively.

RESULTS

The intervention group saw improvements in most symptom measures over the 6 months following cystectomy compared with the control group. Depression and anxiety decreased over the 6-month period for the intervention group patients but increased over this time among the controls (P = 0.01). Fatigue decreased to a minimum for the intervention group participants at 4 months, whereas it peaked at this time for control participants (0.002). Quality-of-life and posttraumatic growth scores followed a similar pattern, with scores peaking at 4 months for the intervention group whereas controls reported their lowest scores at this time (P = 0.01 and P = 0.03, respectively). Changes in pain scores did not reach statistical significance. Neither family caregiver burden nor patient satisfaction showed statistically significant changes over time.

CONCLUSIONS

Patients who received concurrent palliative care in addition to usual urologic care following radical cystectomy for muscle-invasive bladder cancer had better outcomes, including improved fatigue, depression, quality of life, and posttraumatic growth. Although further research on this topic is needed, our results suggest that providing palliative care services in addition to usual urologic care for patients with bladder cancer may significantly reduce postoperative symptoms.

UNLABELLED

We report on the long-term intention-to-treat (ITT) outcome of 118 patients with hepatocellular carcinoma (HCC) undergoing downstaging to within Milan/United Network for Organ Sharing T2 criteria before liver transplantation (LT) since 2002 and compare the results with 488 patients listed for LT with HCC meeting T2 criteria at listing in the same period. The downstaging subgroups include 1 lesion >5 and ≤8 cm (n = 43), 2 or 3 lesions at least one >3 and ≤5 cm with total tumor diameter ≤8 cm (n = 61), or 4-5 lesions each ≤3 cm with total tumor diameter ≤8 cm (n = 14). In the downstaging group, 64 patients (54.2%) had received LT and 5 (7.5%) developed HCC recurrence. Two of the five patients with HCC recurrence had 4-5 tumors at presentation. The 1- and 2-year cumulative probabilities for dropout (competing risk) were 24.1% and 34.2% in the downstaging group versus 20.3% and 25.6% in the T2 group (P = 0.04). Kaplan-Meier's 5-year post-transplant survival and recurrence-free probabilities were 77.8% and 90.8%, respectively, in the downstaging group versus 81% and 88%, respectively, in the T2 group (P = 0.69 and P = 0.66, respectively). The 5-year ITT survival was 56.1% in the downstaging group versus 63.3% in the T2 group (P = 0.29). Factors predicting dropout in the downstaging group included pretreatment alpha-fetoprotein ≥1,000 ng/mL (multivariate hazard ratio [HR]: 2.42; P = 0.02) and Child's B versus Child's A cirrhosis (multivariate HR: 2.19; P = 0.04).

CONCLUSION

Successful downstaging of HCC to within T2 criteria was associated with a low rate of HCC recurrence and excellent post-transplant survival, comparable to those meeting T2 criteria without downstaging. Owing to the small number of patients with 4-5 tumors, further investigations are needed to confirm the efficacy of downstaging in this subgroup.

The autoimmune disease systemic lupus erythematosus has a complex environmental and multifactorial genetic basis. Genome-wide association studies have recently identified numerous disease-associated polymorphisms, but it remains unclear in which cells and during which step of pathogenesis specific polymorphisms interact to cause disease. Using a mouse model in which the same activating mutation (CD45E613R) causes distinct genetic background-dependent disease phenotypes, we performed a screen for genetic modifiers of autoreactivity between anti-nuclear Ab (ANA)-resistant CD45E613R.B6 and ANA-permissive CD45E613R.BALB/c mice. Within a novel autoreactivity-associated locus on chromosome 9, we identify a putative modifier, TLR9. Validating a role for TLR9 in modifying autoreactivity in the context of the CD45E613R mutation, manipulation of TLR9 gene dosage eliminates ANA in CD45E613R.BALB/c mice, but confoundingly permits ANA in CD45E613R.B6 mice. We demonstrate that sensitivity to ANA is modulated by strength of TLR9 signal, because stronger TLR9(B6) signals, but not weaker TLR9(BALB/c) signals, negatively regulate CD45E613R B cell development during competitive reconstitution at the central tolerance checkpoint. Our results identify a novel autoreactivity-associated locus and validate Tlr9 as a candidate gene within the locus. We further demonstrate a novel role for TLR9 signal strength in central tolerance, providing insight into the interplay of disease-associated polymorphisms at a discrete step of systemic lupus erythematosus pathogenesis.

INTRODUCTION/BACKGROUND

Zolpidem is a sedative-hypnotic widely prescribed in the United States. Recently, the US Food and Drug Administration (FDA) issued a drug safety communication regarding its dosing in women.

OBJECTIVE

To compare compliance with FDA-approved dosing for zolpidem in women before and after a drug safety communication, and to evaluate compliance based on pharmacy location and prescriber type.

METHOD

This was a retrospective, observational cohort study. New prescriptions for Ambien, Ambien CR, Edluar, or Zolpimist or their respective generics dispensed from Kerr Drug pharmacies in North Carolina to women 18-64 years of age between April and September of 2012 ("before" cohort) or April and September of 2013 ("after" cohort) were included. χ(2) tests were conducted to assess overall compliance, as well as compliance based on location (urban or rural) and prescriber type (physician or midlevel), with FDA-approved dosing for zolpidem. Trends in total prescription volume and total zolpidem prescription volume for all Kerr Drug pharmacies over the study period were also described.

RESULTS

A total of 14,156 prescriptions for zolpidem were included in the primary analysis. Sixteen percent of prescriptions dispensed were in compliance with FDA recommendations following the FDA alert. A statistically significant increase was observed in compliance with FDA-approved dosing for zolpidem (odds ratio = 1.49; 95% CI, 1.35-1.65; P .0001) postdrug safety communication. Significant increases in compliance were also observed in the post-FDA communication subgroups based on location and prescriber type, though no subgroup was found to be significantly more compliant than another.

CONCLUSIONS

The release of a drug safety communication by the FDA resulted in a statistically significant increase in proper dosing of zolpidem in women. Further research is needed in order to determine the impact of FDA alerts on prescribing patterns and the reasons for therapeutic substitution after such alerts.

OBJECTIVE

To determine national urethroplasty trends based on type of surgery and patient and hospital characteristics. We hypothesized that the number of complex urethroplasty procedures performed has increased over time and may be associated with increased periprocedure complications.

METHODS

The National Inpatient Sample from years 2000 to 2010 was queried for patients with urethroplasty-associated International Classification of Diseases, Ninth Revision, Clinical Modification codes. We analyzed trends in urethroplasty procedures, patient demographics, comorbidities, and hospital characteristics. We evaluated the relationship between patient demographics and comorbid disease, length of hospital stay, hospital charges, and inpatient complications.

RESULTS

During the study period, an estimated 13,700 men (95% confidence interval, 9507-17,894) underwent urethroplasty nationally. Excision with primary anastomosis, buccal graft, and other graft or flap urethroplasty comprised 80.3%, 14.3%, and 5.4%, respectively. Buccal mucosa graft procedures increased over time (P = .03). Only 1.6% of hospitals have ≥ 20 urethroplasties performed annually. Urethroplasty type and urethroplasty volume were not associated with immediate complication rates. Hypertension, diabetes, chronic pulmonary disease, and obesity were the most common comorbidities in urethroplasty patients. Complications during urethroplasty hospitalization occurred in 6.6% of men, with surgical or wound complications being the most common (5.2%). Postoperative mortality was exceedingly rare. Older patients, African Americans, and patients with increased comorbidities were more likely to have complications.

CONCLUSION

An increasing number of buccal mucosa graft urethroplasties occurred over time. Urethroplasty patients have low immediate perioperative morbidity (6.6%) and mortality (0.07%). Patients who are older, African American, or have more comorbid conditions have greater risk for complications.

Burnout and professional dissatisfaction are threats to the primary care workforce. We investigated the relationship between panel management capability, team culture, cynicism, and perceived "do-ability" of primary care among primary care providers (PCPs) and staff in primary care practices. We surveyed 326 PCPs and 142 staff members in 10 county-administered, 6 university-run, and 3 Veterans Affairs primary care clinics in a large urban area in 2013. Predictor variables included capability for performing panel management and perception of team culture. Outcome variables included 2 work experience measures--the Maslach Burnout Inventory cynicism scale and a 1-item measure of the "do-ability" of primary care this year compared with last year. Generalized Estimation Equation (GEE) models were used to account for clustering at the clinic level. Greater panel management capability and higher team culture were associated with lower cynicism among PCPs and staff and higher reported "do-ability" of primary care among PCPs. Panel management capability and team culture interacted to predict the 2 work experience outcomes. Among PCPs and staff reporting high team culture, there was little association between panel management capability and the outcomes, which were uniformly positive. However, there was a strong relationship between greater panel management capability and improved work experience outcomes for PCPs and staff reporting low team culture. Team-based processes of care such as panel management may be an important strategy to protect against cynicism and dissatisfaction in primary care, particularly in settings that are still working to improve their team culture.

BACKGROUND

In the United States, half of men with prostate cancer harbor the androgen-regulated gene fusion TMPRSS2:ERG. We hypothesized that men with TMPRSS2:ERG positive tumors are more responsive to androgen deprivation therapy (ADT).

METHODS

We studied a cohort of 239 men with prostate cancer from the Physicians' Health Study and Health Professionals Follow-up Study who received ADT during their disease course. Fusion status was assessed on available tumor tissue by immunohistochemistry for ERG protein expression. We used Cox models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for assessment of prostate cancer-specific mortality after ADT initiation.

RESULTS

Roughly half of the men had stage T3 or higher tumors at diagnosis and 39% had Gleason 8-10 tumors. During an average follow up of 10.2 years, 42 men died from prostate cancer. There was a non-significant inverse association between positive fusion status and time to death from prostate cancer after ADT (multivariable HR: 0.76; 95% CI: 0.40-1.45). Harboring the TMPRSS2:ERG fusion was associated with a statistically significant lower risk of prostate cancer mortality among men who were treated with orchiectomy (multivariable HR: 0.13; 95% CI: 0.03-0.62), based on 15 events.

CONCLUSIONS

Our results, combined with those from earlier studies, provide suggestive evidence that men with TMPRSS2:ERG positive tumors may have longer prostate cancer survival after ADT. Larger cohorts are needed for more robust results and to assess whether men with tumors harboring the fusion benefit from treatment with ADT in the (neo) adjuvant or metastatic setting specifically.