Comparison of a Low,Fixed Dose and a High,Weight-Based Dose of Recombinant Factor VIIa in the Treatment of Warfarin-Associated Intracranial Hemorrhage

Background

Recombinant activated Factor VII (rFVIIa) can be used for rapid INR normalization in patients with warfarin-associated intracranial hemorrhage (WA-ICH); however, the optimal dose to normalize INR has not been established.

Methods

This is a retrospective review comparing two rFVIIa hospital protocols for WA-ICH [weight-based dose (80 mcg/kg) or fixed dose (2 mg)]. Primary endpoint was the percentage of patients with INR reversal (INR <1.3) at the next INR draw and the need for further doses of rFVIIa. Secondary endpoints included time to documented INR reversal and sustained INR normalization, morbidity, mortality, change in hematoma size, cost, and adverse drug reactions.

Results

Twenty-nine patients were included in each group. The weight-based group received a mean dose of 78.9 ± 21 mcg/kg versus 26.6 ± 8 mcg/kg in the fixed dose group. More patients in the fixed dose protocol achieved documented INR reversal than those in the weight-based group (92.6 vs 72.4 %, p = 0.19). The weight-based group achieved INR normalization in 229.5 [102, 331] minutes versus 165 [83, 447] minutes in the fixed dose group (p=0.02). Time to sustained INR normalization was similar in both groups. Four patients in the fixed dose group received an additional dose of 1 mg per hospital protocol. With the exception of medication acquisition cost savings of about $4,300 per patient who received fixed dose protocol, all other endpoints were similar between groups.

Conclusions

A low, fixed dose of rFVIIa appears to be as effective as a high, weight-based dose in achieving INR normalization in patients with WA-ICH.     

Cost effectiveness of radiofrequency microremodeling for stress urinary incontinence

Introduction and hypothesis

Stress urinary incontinence (SUI) is a common and growing problem among adult women and affects individuals and society through decreased quality of life (QoL), decreased work productivity, and increased health care costs. A new, nonsurgical treatment option has become available for women who have failed conservative therapy, but its cost effectiveness has not been evaluated. This study examined the cost effectiveness of transurethral radiofrequency microremodeling of the female bladder neck and proximal urethra compared with synthetic transobturator tape (TOT), retropubic transvaginal tape (TVT) sling, and Burch colposuspension surgeries for treating SUI.

Methods

A Markov model was used to compare the cost effectiveness of five strategies for treating SUI for patients who had previously failed conservative therapy. The strategies were designed to compare the value of starting with a less invasive treatment. The cost-effectiveness analysis was conducted from the health care system perspective. Efficacy and adverse event rates were obtained from the literature; reimbursement costs were based on Medicare fee schedule. The model cycle was 3 months, with a 3-year time horizon. Single-variable sensitivity analyses were conducted to assess stability of base-case results.

Results

Two of the five strategies employed the use of transurethral radiofrequency microremodeling and achieved 17–30 % lower mean costs relative to their comparative sling or Burch strategies.

Conclusions

Superior safety and cost effectiveness are recognized when patients are offered a sequential approach to SUI management that employs transurethral radiofrequency microremodeling before invasive surgical procedures. This sequential approach is consistent with treatment strategies for other conditions and offers a solution for women with SUI who want to avoid the inherent risks and costs of invasive continence surgery.     

Antimicrobial and antileishmanial activities of hypocrellins A and B

Hypocrellins A and B were evaluated for in vitro antimicrobial and antileishmanial activities. Hypocrellin A exhibited promising activity against Candida albicans and moderate activity against Staphylococcus aureus, methicillin-resistant S. aureus, Pseudomonas aeruginosa, and Mycobacterium intracellulare. Hypocrellin B showed weak antimicrobial activities. Hypocrellin A exhibited potent antileishmanial activity, while hypocrellin B was only moderately active. These results of promising antifungal and antileishmanial activity of hypocrellin A may be useful for further structure-activity relationship and in vivo studies.     

General in-situation safety behaviors are uniquely associated with post-event processing

Background and objectives

Research suggests that state anxiety and in-situation safety behaviors are associated with post-event processing (PEP) in social anxiety. Past research has obtained mixed results on whether one or both factors contribute to PEP. The current investigation evaluated state anxiety and in-situation safety behaviors (including subtypes of in-situation safety behaviors) simultaneously to determine their relative contributions to PEP.

Methods

A prospective study assessed social anxiety, state anxiety, in-situation safety behaviors, PEP, and depression in the context of a speech stressor.

Results

Consistent with theory, in-situation safety behaviors were uniquely associated with greater PEP. State anxiety was not uniquely associated with PEP. Furthermore, restricting and active subtypes of in-situation safety behaviors showed specificity to PEP.

Limitations

Limitations of the present study include the use of a nonclinical analog sample and retrospective reporting of PEP.

Conclusions

These findings highlight the importance of research on in-situation safety behaviors as a potential contributor to PEP.     

Comparing algorithms for deriving psychosis diagnoses from longitudinal administrative clinical records

Purpose

Registers derived from administrative datasets are valuable tools in psychosis research, but diagnostic accuracy can be problematic. We sought to compare the relative performance of four methods for assigning a single diagnosis from longitudinal administrative clinical records when compared with reference diagnoses.

Methods

Diagnoses recorded in inpatient and community mental health records were compared to research diagnoses of psychotic disorders obtained from semi-structured clinical interviews for 289 persons. Diagnoses were derived from administrative datasets using four algorithms; ‘At least one’ diagnosis, ‘Last’ or most recent diagnosis, ‘Modal’ or most frequently occurring diagnosis, and ‘Hierarchy’ in which a diagnostic hierarchy was applied. Agreements between algorithm-based and reference diagnoses for overall presence/absence of psychosis and for specific diagnoses of schizophrenia, schizoaffective disorder, and affective psychosis were examined using estimated prevalence rates, overall agreement, ROC analysis, and kappa statistics.

Results

For the presence/absence of psychosis, the most sensitive and least specific algorithm (‘At least one’ diagnosis) performed best. For schizophrenia, ‘Modal’ and ‘Last’ diagnoses had greatest agreement with reference diagnosis. For affective psychosis, ‘Hierarchy’ diagnosis performed best. Agreement between clinical and reference diagnoses was no better than chance for diagnoses of schizoaffective disorder. Overall agreement between administrative and reference diagnoses was modest, but may have been limited by the use of participants who had been screened for likely psychosis prior to assessment.

Conclusion

The choice of algorithm for extracting a psychosis diagnosis from administrative datasets may have a substantial impact on the accuracy of the diagnoses derived. An ‘Any diagnosis’ algorithm provides a sensitive measure for the presence of any psychosis, while ‘Last diagnosis’ is more accurate for specific diagnosis of schizophrenia and a hierarchical diagnosis is more accurate for affective psychosis.     

Perioperative Breast MRI Is Not Associated with Lower Locoregional Recurrence Rates in DCIS Patients Treated With or Without Radiation

Introduction

For women with ductal carcinoma in situ (DCIS) undergoing breast-conserving surgery (BCS), the benefit of magnetic resonance imaging (MRI) remains unknown. Here we examine the relationship of MRI and locoregional recurrence (LRR) and contralateral breast cancer (CBC) for DCIS treated with BCS, with and without radiotherapy (RT).

Methods

A total of 2,321 women underwent BCS for DCIS from 1997 to 2010. All underwent mammography, and 596 (26 %) also underwent perioperative MRI; 904 women (39 %) did not receive RT, and 1,391 (61 %) did. Median follow-up was 59 months, and 548 women were followed for ≥8 years. The relationship between MRI and LRR was examined using multivariable analysis.

Results

There were 184 LRR events; 5- and 8-year LRR rates were 8.5 and 14.6 % (MRI), respectively, and 7.2 and 10.2 % (no-MRI), respectively (p = 0.52). LRR was significantly associated with age, menopausal status, margin status, RT, and endocrine therapy. After controlling for these variables and family history, presentation, number of excisions, and time period of surgery, there remained no trend toward association of MRI and lower LRR [hazard ratio (HR) 1.18, 95 % confidence interval (CI) 0.79–1.78, p = 0.42]. Restriction of analysis to the no-RT subgroup showed no association of MRI with lower LRR rates (HR 1.36, 95 % CI 0.78–2.39, p = 0.28). No difference in 5- or 8-year rates of CBC was seen between the MRI (3.5 and 3.5 %) and no-MRI (3.5 and 5.1 %) groups (p = 0.86).

Conclusions

We observed no association between perioperative MRI and lower LRR or CBC rates in patients with DCIS, with or without RT. In the absence of evidence that MRI improves outcomes, the routine perioperative use of MRI for DCIS should be questioned.     

Characterization and Treatment of Local Recurrence Following Breast Conservation for Ductal Carcinoma In Situ

Purpose

The optimal treatment strategy for ductal carcinoma in situ (DCIS) continues to evolve and should consider the consequences of initial treatment on the likelihood, type, and treatment of recurrences.

Methods

We conducted a retrospective cohort study using two data sources of patients who experienced a recurrence (DCIS or invasive cancer) following breast-conserving surgery (BCS) for index DCIS: patients with an index DCIS diagnosed from 1997 to 2008 at the academic institutions of the National Comprehensive Cancer Network (NCCN; N = 88) and patients with an index DCIS diagnosed from 1990 to 2001 at community-based integrated healthcare delivery sites of the Health Maintenance Organization Cancer Research Network (CRN) (N = 182).

Results

Just under half of local recurrences in both cohorts were invasive cancer. While 40 % of patients in both cohorts underwent mastectomy alone at recurrence, treatment of the remaining patients varied. In the earlier CRN cohort, most other patients underwent repeat BCS (39 %) with only 18 % receiving mastectomy with reconstruction, whereas only 16 % had repeat BCS and 44 % had mastectomy with reconstruction in the NCCN cohort. Compared with patients not treated with radiation, those who received radiation for index DCIS were less likely to undergo repeat BCS (NCCN: 6.6 vs. 37 %, p = 0.001; CRN: 20 vs. 48 %, p = 0.0004) and more likely to experience surgical complications after treatment of recurrence (NCCN: 15 vs. 4 %, p = 0.17; CRN: 40 vs. 25 %, p = 0.09).

Conclusion

We found that treatment of recurrences after BCS and subsequent complications may be affected by the use of radiotherapy for the index DCIS. Initial treatment of DCIS may have long-term implications that should be considered.     

Management of Positive Sub‐areolar/Nipple Duct Margins in Nipple‐Sparing Mastectomies

We evaluated management of positive sub‐areolar/nipple duct margins in nipple‐sparing mastectomies (NSM) at our institution. Retrospective chart review of all NSM from January 2007 to April 2012 was performed and patient, tumor, and treatment information was collected. Sub‐areolar/nipple duct margins included ductal tissue from within the nipple. Of 438 NSM, 22 (5%) had positive sub‐areolar/nipple duct margins; 21 of 220 cancer‐bearing breasts (10%) and 1 of 218 prophylactic mastectomies (0.5%). Positive margins included four with invasive lobular carcinoma and 18 with ductal carcinoma in situ (DCIS). Management included removal of eight nipples and nine nipple areola complexes (NAC). Four of 17 nipple/NAC specimens had evidence of residual DCIS and none had residual invasive cancer. The majority of nipple/NAC specimens excised for a positive margin had no residual malignancy. Future studies are needed to determine the extent of NAC tissue removal required for positive margins.