Citations

Object The aim in this study was to describe the clinical presentation, differential diagnosis, and risk for neurofibromatosis Type 2 (NF2) in pediatric patients presenting with cerebellopontine angle (CPA) and internal auditory canal (IAC) tumors. Methods The authors conducted a retrospective study at a tertiary care academic referral center. All patients with an age ≤ 18 years who had presented with an extraaxial CPA or IAC tumor between 1987 and 2012 were included in the study cohort. Data regarding symptoms, diagnosis, tumor characteristics, and NF2 status were collected and analyzed. Results Sixty patients (55% female, 45% male) harboring 87 tumors were identified. The mean age at diagnosis was 12.8 years (median 14.0 years, range 0.9–18.9 years). Schwannomas were the most commonly identified lesions (57 of 87 tumors, including 52 vestibular, 3 facial, and 2 trigeminal schwannomas), followed by meningiomas (5 of 87) and epidermoid cysts (4 of 87). Six malignant tumors were diagnosed, including small-cell sarcoma, squamous cell carcinoma, malignant meningioma, atypical rhabdoid-teratoid tumor, endolymphatic sac tumor, and malignant ganglioglioma. Headache, followed by hearing loss and imbalance, was the most common presenting symptom, whereas dysphagia, otalgia, and facial pain were uncommon. Neurofibromatosis Type 2 was diagnosed in 20 (61%) of 33 patients with vestibular schwannoma (VS), while the other 13 patients (39%) had sporadic tumors. Nineteen of the 20 patients with NF2 met the diagnostic criteria for that disorder on initial presentation, and 15 of them presented with bilateral VS. At the last follow-up, 19 of the 20 patients subsequently diagnosed with NF2 demonstrated bilateral VSs, whereas 1 patient with a unilateral VS and multiple other NF2-associated tumors has yet to demonstrate a contralateral VS to date. Only 1 patient presenting with an isolated unilateral VS and no family history of NF2 demonstrated a contralateral VS on subsequent radiological screening. Conclusions Cerebellopontine angle and IAC tumors in the pediatric population are rare. There are several noteworthy differences between the adult and pediatric populations harboring these lesions. While VS is the most common pathology in both age groups, the lesion was found in only 60% of the pediatric patients in the present study. Unlike in adults, VSs in the pediatric population were associated with NF2 in over one-half of all cases. The majority of pediatric patients with NF2 fulfilled the diagnostic criteria at initial presentation; however, approximately 7% of patients presenting with a seemingly sporadic (no family history of NF2) unilateral VS will meet the criteria for NF2 later in life. Finally, malignancies account for a significantly higher percentage (10%) of cases among pediatric patients. These findings underscore the importance of early screening and close radiological follow-up and may be helpful in patient counseling.

AbstractHigh stress is a prevalent problem in the worksite. To reduce stress, improve productivity, reduce absenteeism, and lower healthcare costs, many companies offer exercise classes or stress management programmes. Although physical activity is an important component of stress management, few worksites have integrated physical activity into their comprehensive stress reduction programmes. The purpose of this single‐arm pilot project was to examine the potential effectiveness of an integrated exercise (studio cycling) and cognitive–behavioural stress management programme. Eighty‐four adults, 75% female, mostly aged 40+ years, participated in an integrated 12‐week cycling studio and cognitive–behavioural stress management programme. Participants experienced a significant and clinically meaningful reduction on the Perceived Stress Scale (p < 0.01), rating of current stress level and confidence to manage stress at the programme's end and at a 1‐month follow‐up. Participants also reported having significantly improved overall health, improved nutritional habits, higher physical activity level, greater confidence in their ability to follow a healthy diet, higher spiritual well‐being, improved sleep, receiving more support for maintaining healthy living and improved quality of life at the completion of the 12‐week programme and 1‐month follow‐up. These findings provide further support for an integrated exercise and stress management programme. Copyright © 2013 John Wiley & Sons, Ltd.

Purpose This study sought to characterize transformation incidence and outcome for patients with follicular lymphoma (FL) in a prospective observational series begun after diffusion of rituximab use. Patients and Methods Patients with newly diagnosed FL were prospectively enrolled onto the University of Iowa/Mayo Clinic Specialized Program of Research Excellence Molecular Epidemiology Resource from 2002 to 2009. Patients were actively followed for re-treatment, clinical or pathologic transformation, and death. Risk of transformation was analyzed via time to transformation by using death as a competing risk. Results In all, there were 631 patients with newly diagnosed grade 1 to 3a FL who had a median age at enrollment of 60 years. At a median follow-up of 60 months (range, 11 to 110 months), 79 patients had died, and 60 patients developed transformed lymphoma, of which 51 were biopsy proven. The overall transformation rate at 5 years was 10.7%, with an estimated rate of 2% per year. Increased lactate dehydrogenase was associated with increased risk of transformation. Transformation rate at 5 years was highest in patients who were initially observed and lowest in patients who initially received rituximab monotherapy (14.4% v 3.2%; P = .021). Median overall survival following transformation was 50 months and was superior in patients with transformation greater than 18 months after FL diagnosis compared with patients with earlier transformation (5-year overall survival, 66% v 22%; P < .001). Conclusion Follicular transformation rates in the immunochemotherapy era are similar to risk of death without transformation and may be lower than reported in older series. Post-transformation prognosis is substantially better than described in older series. Initial management strategies may influence the risk of transformation.

Object The goals of this study were to report the clinical presentation, radiographic findings, operative strategy, and outcomes among patients with temporal bone encephaloceles and cerebrospinal fluid fistulas (CSFFs) and to identify clinical variables associated with surgical outcome. Methods A retrospective case series including all patients who underwent a middle fossa craniotomy or combined mastoid–middle cranial fossa repair of encephalocele and/or CSFF between 2000 and 2012 was accrued from 2 tertiary academic referral centers. Results Eighty-nine consecutive surgeries (86 patients, 59.3% women) were included. The mean age at time of surgery was 52.3 years, and the left side was affected in 53.9% of cases. The mean delay between symptom onset and diagnosis was 35.4 months, and the most common presenting symptoms were hearing loss (92.1%) and persistent ipsilateral otorrhea (73.0%). Few reported a history of intracranial infection (6.7%) or seizures (2.2%). Thirteen (14.6%) of 89 cases had a history of major head trauma, 23 (25.8%) were associated with chronic ear disease without prior operation, 17 (19.1%) occurred following tympanomastoidectomy, and 1 (1.1%) developed in a patient with a cerebral aqueduct cyst resulting in obstructive hydrocephalus. The remaining 35 cases (39.3%) were considered spontaneous. Among all patients, the mean body mass index (BMI) was 35.3 kg/m2, and 46.4% exhibited empty sella syndrome. Patients with spontaneous lesions were statistically significantly older (p = 0.007) and were more commonly female (p = 0.048) compared with those with nonspontaneous pathology. Additionally, those with spontaneous lesions had a greater BMI than those with nonspontaneous disease (p = 0.102), although this difference did not achieve statistical significance. Thirty-two surgeries (36.0%) involved a middle fossa craniotomy alone, whereas 57 (64.0%) involved a combined mastoid–middle fossa repair. There were 7 recurrences (7.9%); 2 patients with recurrence developed meningitis. The use of artificial titanium mesh was statistically associated with the development of recurrent CSFF (p = 0.004), postoperative wound infection (p = 0.039), and meningitis (p = 0.014). Also notable, 6 of the 7 cases with recurrence had evidence of intracranial hypertension. When the 11 cases that involved using titanium mesh were excluded, 96.2% of patients whose lesions were reconstructed with an autologous multilayer repair had neither recurrent CSFF nor meningitis at the last follow-up. Conclusions Patients with temporal bone encephalocele and CSFF commonly present with persistent otorrhea and conductive hearing loss mimicking chronic middle ear disease, which likely contributes to a delay in diagnosis. There is a high prevalence of obesity among this patient population, which may play a role in the pathogenesis of primary and recurrent disease. A middle fossa craniotomy or a combined mastoid–middle fossa approach incorporating a multilayer autologous tissue technique is a safe and reliable method of repair that may be particularly useful for large or multifocal defects. Defect reconstruction using artificial titanium mesh should generally be avoided given increased risks of recurrence and postoperative meningitis.

ABSTRACTBackgroundPrescription drug abuse has prompted considerable concern. We evaluated a retrospective drug utilization review program to reduce controlled substance use among individuals with high‐risk utilization.MethodsWe analyzed pharmacy claims from a large pharmaceutical benefits manager. For each eligible member, we calculated a controlled substance score based on the number and type of claims, prescribers and pharmacies, and utilization patterns over three months. Two state health plans sent controlled substance letters to prescribers of members meeting or exceeding a plan‐ and pre‐specified controlled substance score. Two different state health plans did not send such letters. We used a difference‐in‐difference design and generalized estimating equations to quantify the impact of the program on the mean difference in reduction of the controlled substance score over six months.ResultsEligible members in the intervention and comparison states had similar baseline mean controlled substance scores (19.0 vs. 18.6, p = 0.36). Adjusting for individuals' age, sex and pharmacy risk group score, reductions in the mean controlled substance score were greater in the intervention than comparison cohort (5.67 vs. 4.31, p = 0.01), corresponding with a 34.0% reduction in the intervention cohort compared to a 25.5% reduction in the comparison cohort. Changes were driven primarily by reductions in the number of controlled substance claims filled (30.5% vs. 23.1%, p = 0.01), as well as by a non‐statistically significant trend towards reductions in the number of prescribers and pharmacies used (26.9% vs. 20.1%, p = 0.07).ConclusionsRetrospective drug utilization review programs may reduce controlled substance scores and claims among individuals with patterns suggesting high‐risk utilization. Copyright © 2013 John Wiley & Sons, Ltd.

Abstract Background: Epithelial ovarian cancer (EOC) is the fifth leading cause of cancer-related death in females and leading gynecologic cause of cancer-related death. Despite the identification of a number of serum biomarkers, methods to identify early-stage disease and predict prognosis remain scarce. We have evaluated two biologically connected serum biomarkers, serum leukocyte protease inhibitor (SLPI) and progranulin (PGRN). Methods: Two-hundred frozen plasma samples were acquired from the Mayo Clinic Biospecimen Repository for Ovarian Cancer Research. Samples were obtained from 50 patients with benign conditions, 50 with American Joint Committee on Cancer (AJCC) stage I and II EOC, and 100 with AJCC stage III and IV EOC. Samples were obtained before surgical resection of a mass and were analyzed for absolute levels of SLPI and PGRN using ELISA assays. Receiver-operator characteristic curves were generated for SLPI and PGRN. Median follow-up was 48 months. Results: Absolute levels of SLPI were significantly elevated in patients with EOC compared with benign disease and predicted the presence of EOC (AUC of 0.812; P = 0.04); SLPI remained elevated in the subset of patients with normal CA-125. PGRN levels were not significantly increased in patients with early-stage or late-stage EOC as a whole, but an increase in PGRN levels was associated with decreased overall survival in advanced EOC. Conclusions: SLPI levels are elevated in EOC, and SLPI shows promise as a diagnostic biomarker for patients with both elevated and normal CA-125 levels. An increase in PGRN is associated with decreased overall survival. Impact: SLPI is elevated in EOC and warrants investigation in a screening study in women at risk for EOC. Cancer Epidemiol Biomarkers Prev; 22(10); 1730–5. ©2013 AACR.

Object The authors' objective was 2-fold: 1) to compare outcomes of microsurgical resection for vestibular schwannoma (VS) between patients aged 70 years or older and patients younger than 70 years and 2) to test the hypothesis that symptomatic tumors in elderly patients represent a more aggressive variant of VS than those in younger adults, resulting in increased morbidity and a higher rate of recurrence after subtotal resection (STR). Methods A retrospective matched cohort study was conducted. Patients aged 70 years or older who had undergone microsurgical resection of VS were matched to adult patients younger than 70 years; the matching was performed on the basis of surgical approach, completeness of resection, and tumor size. Associations between clinical, radiographic, and surgical data and postoperative outcome were analyzed using conditional logistic regression. Results Twenty patients aged 70 years or older (mean age ± SD 75.9 ± 5.3, range 70–86 years) were identified and matched to a cohort of younger adult patients (mean age ± SD 55.7 ± 13.8, range 25–69 years). The mean tumor size in both groups was approximately 3 cm. Overall, the elderly patients had a poorer preoperative American Society of Anesthesiology physical status score (p = 0.038), were more likely to report imbalance (OR 9.61, p = 0.016), and more commonly exhibited compromised balance and coordination (OR 9.61, p = 0.016) than patients in the younger cohort. There were no differences between the 2 cohorts in perioperative complications (p = 0.26) or facial nerve function (p > 0.5) at any time. The elderly patients were 13 times more likely to have long-term postoperative imbalance (OR 13.00, p = 0.013) than the younger patients. Overall, 9 tumors recurred among 32 patients undergoing STR; 6 of these patients underwent additional interventions (stereotactic radiosurgery in 5 patients and microsurgery in 1) and showed no evidence of tumor progression at the last follow-up. The median growth rate of the recurrent tumor in the 6 elderly patients was 4.8 mm/year (range 2.1–14.9 mm/year) and, in the 3 control patients, 2.2 mm/year (range 1.9–4.0 mm/year). Overall, the mortality data showed a trend toward statistical significance (p = 0.068) with a higher risk of death in the elderly. Conclusions As the number of elderly patients with VS increases, microsurgical resection will remain an important management option for these patients. Despite a poorer preoperative physical status in elderly patients, their morbidity profiles are similar to those in adult patients younger than 70 years. However, elderly patients may require longer convalescence due to prolonged postoperative imbalance. Not surprisingly, overall diminished functional reserve and advanced comorbidities may increase the mortality risk associated with surgical intervention in the elderly patients. Finally, there was a high risk of further tumor growth following STR in the elderly patients (6 [37.5%] of 16), underscoring the need for close postoperative radiological surveillance and consideration of early stereotactic radiosurgery for the tumor remnant following the STR.

Collaborative care management (CCM) for depression has been demonstrated to improve clinical outcomes. The impetus for this study was to determine if outpatient utilization patterns would be associated with depression outcomes. The hypothesis was that depression remission would be independently correlated with outpatient utilization at 6 and 12 months after enrollment into CCM. The study was a retrospective chart review analysis of 773 patients enrolled into CCM with 6- and 12-month follow-up data. The data set comprised baseline demographic data, patient intake self-assessment scores (Patient Health Questionnaire [PHQ-9], Generalized Anxiety Disorder-7, Mood Disorder Questionnaire, and Alcohol Use Disorders Identification Test), the number of outpatient visits, and follow-up PHQ-9 scores. To control for individual patient complexity and pattern of usage, the number of outpatient visits for 6 months prior to enrollment also was measured. With a logistic regression model for outpatient visit outlier status as the dependent variable, remission at 6 months (odds ratio [OR] 0.519, CI [confidence interval] 0.349–0.770, P =0.001) and remission at 12 months (OR 0.573, CI 0.354–0.927, P =0.023) were predictive. With this inverse relationship between remission and outlier status, those patients who were not in remission had an OR of 1.928 for outpatient visit outlier status at 6 months after enrollment and an OR of 1.745 at 12 months. Patients who improved clinically to remission while in CCM had decreased odds of outlier status for outpatient utilization at 6 and 12 months when controlling for all other study variables. Improvement in health care outcomes by CCM could translate into decreased outpatient utilization for depressed patients. ( Population Health Management 2014;17:48–53)