Cost minimization analysis of nasopharyngoscope reprocessing in community practice.

BACKGROUND: Reprocessing of nasopharyngoscopes represents a large financial burden to community physicians. The aim of this study was to perform a cost analysis of nasopharyngoscope reprocessing methods at the community level. METHODS: Electronic surveys were distributed by email to community otolaryngologists. Surveys were comprised of 14 questions assessing clinic size, nasopharyngoscope volume, scope reprocessing method and maintenance. Four manual techniques were evaluated: (1) soak with ortho-phthalaldehyde solution (Cidex-OPA; Advanced Sterilization Products, Johnson and Johnson Inc., Markham, Canada), (2) soak with accelerated hydrogen peroxide solution (Revital-Ox; Steris Canada Inc., Mississauga, Canada), (3) disinfection with chlorine dioxide wipe (Tristel Trio Wipes System; Tristel plc., Cambridgeshire, UK), (4) UV-C light system (UV Smart, Delft, The Netherlands). All costs are reported in CAD, and consumable and capital costs for reprocessing methods were obtained from reported vendor prices. Time costs were derived from manufacturer recommendations, the Ontario Medical Association Physician's Guide to Uninsured Services, and the Ontario Nurses Association Collective Agreement. Cost analyses determined the most cost-effective reprocessing method in the community setting. Sensitivity analyses assessed the impact of reprocessing volume and labour costs. RESULTS: Thirty-six (86%) otolaryngologists responded and answered the survey. The cost per reprocessing event for Cidex-OPA, Revital-Ox, Tristel and UV system were $38.59, $26.47, $30.53, and $22.74 respectively when physicians reprocessed their endoscopes themselves. Sensitivity analyses demonstrated that Revital-Ox was the least costly option in a low volume, however, the UV system remained the most cost effective in higher volumes. The cost per reprocessing event when done by clinic staff was $5.51, $4.42, $11.23 and $6.21 for Cidex-OPA, Revital-Ox, Tristel and the UV system. CONCLUSIONS: The UV light system appears to be the most cost-effective method in high volumes of reprocessing, and Revital-Ox is cheaper in lower volumes and when performed by clinic staff rather than physicians. It is important to consider the anticipated work volume, shared clinic space and number of co-workers prior to choosing a reprocessing method.

Recognizing BRCA gene mutation risk subsequent to breast cancer diagnosis in southwestern Ontario.

OBJECTIVE: To describe the population of women in southwestern Ontario who were diagnosed with potentially preventable BRCA mutation-related breast cancer. DESIGN: Retrospective chart review. SETTING: The Cancer Genetics Clinic of the London Regional Cancer Program in London, Ont. PARTICIPANTS: Patients younger than 52 years of age who were referred to the London Regional Cancer Program Cancer Genetics Clinic between 1997 and 2007 for BRCA testing after being diagnosed with breast cancer (N = 1017). MAIN OUTCOME MEASURES: The proportion of women with BRCA1 or BRCA2 gene mutations and the proportion of women who would have qualified, based on family cancer history, for referral for genetic counseling and testing before their breast cancer diagnoses. RESULTS: Among the 1017 women referred for BRCA testing, 63 women younger than 52 years of age who had been diagnosed with breast cancer were found, subsequent to this diagnosis, to have BRCA1 or BRCA2 gene mutations. Of these, 41 (65%) had family cancer histories that would have qualified them for genetic counseling and testing, according to provincial criteria, before their own breast cancer diagnoses. Of the 63 women, most (81%) had been referred for BRCA gene mutation testing by their oncologists or surgeons. CONCLUSION: Our results suggest that the diagnosis of breast cancer could have been anticipated, and perhaps in some cases prevented, in up to two-thirds of high-risk women younger than 52 years of age in southwestern Ontario. If the high-risk status of these women had been recognized, they might have had the opportunity to choose genetic counseling, testing, more effective cancer surveillance, and potentially preventive options. The results of this study call for increased public and care provider awareness about hereditary breast cancer risk to promote women's ability to choose to access genetic counseling.

Glycogen synthase kinase 3beta regulation of nuclear factor of activated T-cells isoform c1 in the vascular smooth muscle cell response to injury.

The migration and proliferation of vascular smooth muscle cells (vSMCs) are critical events in neointima formation during atherosclerosis and restenosis. The transcription factor nuclear factor of activated T-cells-isoform c1 (NFATc1) is regulated by atherogenic cytokines, and has been implicated in the migratory and proliferative responses of vSMCs through the regulation of gene expression. In T-cells, calcineurin de-phosphorylates NFATc1, leading to its nuclear import, while glycogen synthase kinase 3 beta (GSK3beta) phosphorylates NFATc1 and promotes its nuclear export. However, the relationship between NFATc1 and GSK3beta has not been studied during SMC migration and proliferation. We investigated this by scrape wounding vSMCs in vitro, and studying wound repair. NFATc1 protein was transiently increased, reaching a peak at 8 h after wounding. Cell fractionation and immunocytochemistry revealed that NFATc1 accumulation in the nucleus was maximal at 4 h after injury, and this was coincident with a significant 9 fold increase in transcriptional activity. Silencing NFATc1 expression with siRNA or inhibition of NFAT with cyclosporin A (CsA) attenuated wound closure by vSMCs. Phospho-GSK3beta (inactive) increased to a peak at 30 min after injury, preceding the nuclear accumulation of NFATc1. Overexpression of a constitutively active mutant of GSK3beta delayed the nuclear accumulation of NFATc1, caused a 50% decrease in NFAT transcriptional activity, and attenuated vSMC wound repair. We conclude that NFATc1 promotes the vSMC response to injury, and that inhibition of GSK3beta is required for the activation of NFAT during wound repair.

Use of the microdebrider in the surgical management of rhinophyma.

Rhinophyma is a disfiguring end-stage manifestation of acne rosacea. It is characterized by a painless hyperplasia of the sebaceous glands and connective tissues of the nose. Numerous surgical modalities-including scalpel surgery, dermabrasion, CO2 laser ablation, and electrocautery-have been reported with varying results. We describe our experience with using a microdebrider to treat 2 patients-a 65-year-old man and a 74-year-old man-who presented with rhinophyma. The instrument we used was the Medtronic Straightshot M4 Microdebrider. Using a low revolution speed, we easily excised the bulky superficial tissue. At higher revolution speeds with the use of a small shaver tip, we were able to achieve delicate contouring of the nasal tip and ala without causing scarring. Postoperatively, both patients exhibited an excellent cosmetic outcome and expressed a high degree of patient satisfaction. We conclude that the microdebrider is an excellent surgical tool for treating rhinophyma lesions. Its ease of use and its availability at most surgical centers makes it a favorable surgical option.

Epigenetic mechanisms in the dopamine D2 receptor-dependent inhibition of the prolactin gene.

Transcription of the prolactin gene is dynamically controlled by positive and negative hormone signals that target the regulatory promoter region. Based on the inducibility of prolactin gene expression by inhibitors of histone deacetylases (HDACs), we examined the role of histone acetylation at the genomic prolactin promoter as a late step in transcriptional regulation. Chromatin immunoprecipitation analysis of GH4 cells revealed elevated levels of acetylated histones in the promoter and enhancer regions of the gene, compared with downstream intron sequences. 17beta-Estradiol stimulated histone H4 acetylation in the promoter region by 2- to 3-fold within 30 min. Dopamine inhibited histone H4 acetylation by 2-fold in 30 min, an effect mimicked by the MAPK kinase (MEK1) inhibitor U0126. In contrast, the synthetic glucocorticoid dexamethasone, which inhibits prolactin transcription, failed to alter histone acetylation over the same time frame. Association of transcription activator Pit-1 with the prolactin promoter was unchanged by hormone treatment. However, in response to dopamine, histone deacetylase HDAC2 and corepressor mSin3A were rapidly recruited to the prolactin promoter, and association was sustained above basal levels over a 1-h period. Consistent with this corepressor function, depletion of endogenous mSin3A by small interfering RNA was sufficient to enhance prolactin gene expression by 70%, comparable to the induction by the HDAC inhibitor, trichostatin A. These studies demonstrate that dopamine D2 receptor activation and inhibition of MAPK (ERK1/2) signaling lead to rapid deacetylation of histones at the genomic prolactin promoter. Recruitment of specific HDAC/ corepressor complexes may be an important mechanism for repression of target gene transcription by Gi/o-coupled receptors.

Discontinuing routine histopathological analysis after adult tonsillectomy for benign indication.

OBJECTIVE: This study examines the rate of occult malignancy in routine histopathological analysis of tonsillectomy specimens from benign surgical cases in adults. STUDY DESIGN: Retrospective data review. METHODS: 181 consecutive charts of tonsillectomies performed for benign indications between March 2007 and March 2014 were reviewed. Data on age, indications for surgery, preoperative and intraoperative clinical findings, and final pathology results were collected. A literature review of studies examining the rate of occult malignancy in tonsillectomy specimens was also performed, and the combined data was pooled. The financial impact of routine tonsil pathological analysis was determined. RESULTS: In 181 patients, there was one case of occult malignancy. After study inclusion and exclusion criteria were met, a review of the literature yielded 3,724 pooled tonsillectomy cases, with no case of unsuspected occult malignancy reported in the literature. The number needed to screen combining our series with the reported literature was 3,904. The financial impact of routine histopathological analysis at our institution was determined to be CAD $3308 per year. CONCLUSION: Routine pathological analysis of tonsil specimens recovered from surgery performed for benign indications, in the absence of any suspicion preoperatively for malignancy, is not supported by current evidence and is not financially sound. Modern evidence does not support the need for even gross specimen analysis in these cases.

High frequency of activating PIK3CA mutations in human papillomavirus-positive oropharyngeal cancer.

IMPORTANCE: Large-scale whole-exome sequencing studies of head and neck squamous cell carcinoma (HNSCC) have established that the disease is dominated by frequent mutations in tumor suppressor genes with rare activating mutations in oncogenes that would be easily targetable with molecular agents. There was evidence in these reports, however, that activating mutations in phosphoinositide 3-kinase catalytic subunit p110α (PIK3CA) were common in patients with human papillomavirus (HPV)-positive tumors. We set out to test this prediction in oropharyngeal patient samples from our institution. OBJECTIVE: To confirm whether activating mutations in PIK3CA are frequent in HPV-positive HNSCC because this mutated oncogene represents a potential therapeutic target. DESIGN, SETTING, AND PARTICIPANTS: A retrospective search of the London Health Sciences Centre pathology database was performed to identify oropharyngeal cancer samples. DNA from pretreatment primary site biopsy samples from 87 patients were tested for high-risk HPV types 16 and 18 by real-time polymerase chain reaction. MAIN OUTCOMES AND MEASURES: Samples were tested for activating mutations at the 3 mutational hot spots (codons 542, 545, and 1047) by polymerase chain reaction followed by Sanger sequencing using forward and reverse primers. RESULTS: Only 4 of 41 HPV-negative tumors (10%) demonstrated PIK3CA hot spot mutations, including 3 at codon 1047 and 1 at codon 542. Of 46 HPV-positive tumors, 13 (28%) demonstrated activating PIK3CA mutations, including 7 at codon 542, 5 at codon 545, and 1 at codon 1047. The difference in PIK3CA mutation frequency was significantly different between HPV-positive and HPV-negative cancers (P = .03). CONCLUSIONS AND RELEVANCE: Although there has been a suggestion that activating PIK3CA mutations are common in HPV-positive HNSCC, to our knowledge, this is the first study to clearly identify this phenomenon. Targeting PIK3CA with molecular agents in HPV-positive patients may be a mechanism to improve cure rates and decrease treatment toxic effects in this rapidly growing cohort of patients.