Use of GlideScope in Patients Undergoing NIM Thyroidectomy.

OBJECTIVES: Thyroidectomy and parathyroidectomy using the nerve integrity monitor (NIM) require proper placement of the endotracheal tube with electrodes aligned correctly within the larynx. The purpose of this study is to determine the percentage of patients who require positional adjustments of the endotracheal tube prior to beginning surgery and to understand the value of using the GlideScope to assure proper NIM tube placement within the larynx. METHODS: This prospective study examines operative data from 297 patients who underwent NIM thyroidectomy and parathyroidectomy. After routine orotracheal intubation by an anesthesiologist and positioning of the patient for surgery, a GlideScope was used to check the position of the tube in 2 planes: depth of tube placement and rotation of the tube within the larynx assuring proper placement of the electromyogram electrodes within the glottis. RESULTS: Tube adjustment was required for 66.5% of patients. In 48.1% of cases, tube retraction or advancement to a proper depth was needed. Tube rotation was required for 30.1% of patients, and 11.8% of patients required both adjustment of tube depth and tube rotation to properly align electrodes. CONCLUSIONS: After the anesthesiologist places the NIM endotracheal tube, and the patient is positioned for surgery, additional tube adjustment is often needed prior to the start of surgery. The GlideScope is readily available in the operating suite, its use adds little time to the procedure, and assures proper NIM tube placement. The use of the GlideScope is recommended.

Long-term safety and efficacy of anacetrapib in patients with atherosclerotic vascular disease.

AIMS: REVEAL was the first randomized controlled trial to demonstrate that adding cholesteryl ester transfer protein inhibitor therapy to intensive statin therapy reduced the risk of major coronary events. We now report results from extended follow-up beyond the scheduled study treatment period. METHODS AND RESULTS: A total of 30 449 adults with prior atherosclerotic vascular disease were randomly allocated to anacetrapib 100 mg daily or matching placebo, in addition to open-label atorvastatin therapy. After stopping the randomly allocated treatment, 26 129 survivors entered a post-trial follow-up period, blind to their original treatment allocation. The primary outcome was first post-randomization major coronary event (i.e. coronary death, myocardial infarction, or coronary revascularization) during the in-trial and post-trial treatment periods, with analysis by intention-to-treat. Allocation to anacetrapib conferred a 9% [95% confidence interval (CI) 3-15%; P = 0.004] proportional reduction in the incidence of major coronary events during the study treatment period (median 4.1 years). During extended follow-up (median 2.2 years), there was a further 20% (95% CI 10-29%; P < 0.001) reduction. Overall, there was a 12% (95% CI 7-17%, P < 0.001) proportional reduction in major coronary events during the overall follow-up period (median 6.3 years), corresponding to a 1.8% (95% CI 1.0-2.6%) absolute reduction. There were no significant effects on non-vascular mortality, site-specific cancer, or other serious adverse events. Morbidity follow-up was obtained for 25 784 (99%) participants. CONCLUSION: The beneficial effects of anacetrapib on major coronary events increased with longer follow-up, and no adverse effects emerged on non-vascular mortality or morbidity. These findings illustrate the importance of sufficiently long treatment and follow-up duration in randomized trials of lipid-modifying agents to assess their full benefits and potential harms. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number (ISRCTN) 48678192; ClinicalTrials.gov No. NCT01252953; EudraCT No. 2010-023467-18.

101 Dothideomycetes genomes: A test case for predicting lifestyles and emergence of pathogens.

Dothideomycetes is the largest class of kingdom Fungi and comprises an incredible diversity of lifestyles, many of which have evolved multiple times. Plant pathogens represent a major ecological niche of the class Dothideomycetes and they are known to infect most major food crops and feedstocks for biomass and biofuel production. Studying the ecology and evolution of Dothideomycetes has significant implications for our fundamental understanding of fungal evolution, their adaptation to stress and host specificity, and practical implications with regard to the effects of climate change and on the food, feed, and livestock elements of the agro-economy. In this study, we present the first large-scale, whole-genome comparison of 101 Dothideomycetes introducing 55 newly sequenced species. The availability of whole-genome data produced a high-confidence phylogeny leading to reclassification of 25 organisms, provided a clearer picture of the relationships among the various families, and indicated that pathogenicity evolved multiple times within this class. We also identified gene family expansions and contractions across the Dothideomycetes phylogeny linked to ecological niches providing insights into genome evolution and adaptation across this group. Using machine-learning methods we classified fungi into lifestyle classes with >95 % accuracy and identified a small number of gene families that positively correlated with these distinctions. This can become a valuable tool for genome-based prediction of species lifestyle, especially for rarely seen and poorly studied species.

Breed is associated with the ABCB1-1Δ mutation in Australian dogs.

OBJECTIVE: The ABCB1 gene encodes P-glycoprotein (P-gp), a cellular membrane pump. One functional mutation that leads to expression of a less functional form of P-gp, ABCB1-1Δ, has been described in dogs. Individuals with this mutation can have severe adverse reactions to common veterinary pharmaceuticals that are known substrates of this pump. We investigated the detection of this mutation in samples submitted to two Australian diagnostic laboratories. METHODS: A total of 4842 dogs across 27 breeds were tested for the ABCB1-1Δ mutation from buccal swabs or EDTA blood using standard PCR, multiplex PCR, or genotyping chip. Statistical analysis was applied to determine the proportions and odds ratios of the ABCB1-1Δ mutation in herding breeds compared with non-herding breeds. RESULTS: The ABCB1-1Δ mutation was detected in nine breeds. The most commonly affected breeds were collies, Australian shepherds, white Swiss shepherds, and Shetland sheepdogs. Of 32 dogs in 18 non-herding breeds tested, one cocker spaniel and one labradoodle were positive for the mutation, both heterozygous. CONCLUSION: The most frequently affected breeds for ABCB1-1Δ mutation are the collie, Australian shepherd, white Swiss shepherd and Shetland sheepdog. As the mutation is associated with an increased incidence of adverse reactions to commonly used pharmaceuticals, veterinarians need to be aware of the breeds at most risk of carrying this mutation and consider testing these individuals prior to administering these medications.

Clinicopathologic features of lingual canine T-zone lymphoma.

Canine T-zone lymphoma (TZL) is a subtype of T-cell lymphoma characterized by unique histologic pattern and cytomorphology, immunophenotypic loss of CD45 expression, and an indolent clinical behaviour. Dogs with TZL typically present with 1 or more enlarged lymph nodes and/or lymphocytosis. We describe a novel extranodal presentation of TZL involving the tongue. Twelve dogs with tongue masses were diagnosed with lingual TZL based on a variable combination of immunophenotyping via flow cytometry, cytology, histopathology, immunohistochemistry and/or PCR for antigen receptor rearrangement (PARR) assay. Eleven dogs exhibited concurrent lymphocytosis and/or lymph node enlargement. Three cases were initially diagnosed as plasma cell tumours based on histology alone, thereby revealing a potential diagnostic challenge. Seven dogs achieved clinical remission and 4 achieved stable disease following variable treatment, consistent with the indolent nature of typical TZL involving the lymph nodes and peripheral blood. In 1 case the TZL resulted in progressive disease and failure to respond to treatment. In this case, the TZL exhibited histologic features of a higher grade neoplasm. This case series highlights a unique presentation of TZL and identifies a new differential diagnosis for lingual neoplasia. In this study, we characterize the clinical presentation, diagnostic features and patient outcomes of 12 dogs with lingual TZL.

Prior joint disease is associated with increased risk of periarticular histiocytic sarcoma in dogs.

Periarticular histiocytic sarcoma (PAHS) is the most common synovial tumour in dogs and is characterized by aggressive local disease with a high rate of distant metastasis. Previously, an association between PAHS and prior joint disease has been demonstrated in the Bernese Mountain Dog breed and suggested in the Rottweiler. We hypothesized that this association would be present in other breeds and investigated this via a retrospective, case-controlled analysis. Cases were dogs diagnosed with PAHS of the stifle or elbow. Controls were age, breed and sex-matched dogs without a diagnosis of histiocytic sarcoma. Diagnosis of prior joint disease was determined based on review of medical records and direct veterinarian and owner communications. Data were evaluated using logistic regression, 2-sampled t tests, and chi-squared analysis. Our study population consisted of 28 cases and 46 controls, including Flat-Coated, Golden and Labrador Retrievers, Rottweilers, English Bulldogs, Shih Tzus, Australian Shepherds, Staffordshire Terriers and mixed breed dogs. Dogs with PAHS were more likely to have prior joint disease in the tumour-affected joint compared with the control population (odds ratio [OR] = 13.42, P < .0001, 95% confidence interval [CI] = 4.33-48.63). A total of 88.2% of dogs with stifle PAHS had prior joint disease in their tumour-affected joint, most commonly cranial cruciate ligament rupture. This study confirms that the previously noted association between prior joint disease and PAHS in Bernese Mountain Dogs also applies to other breeds. Additional studies are needed to further investigate for a causal relationship.

Low-grade gastrointestinal lymphoma in dogs: 20 cases (2010 to 2016).

OBJECTIVES: To report the clinical presentation, treatment and prognosis of dogs with low-grade gastrointestinal lymphoma. MATERIALS AND METHODS: Cases were solicited from the American College of Veterinary Internal Medicine Oncology Diplomate listserv. Medical records of dogs with low-grade gastrointestinal lymphoma diagnosed via a combination of histology and immunohistochemistry with or without analysis of polymerase chain reaction for antigen receptor rearrangement were included. Signalment, clinical signs, diagnostic test results, chemotherapy protocol, response to treatment, date of first progression, rescue therapies and date and cause of death or last follow-up visit were collected. RESULTS: Twenty cases were included. Males and small breed dogs were over-represented. Frequent clinical signs included weight loss, vomiting and diarrhoea. Most lymphomas were T-cell phenotype (95%), and epitheliotropism was commonly described (60%). Immunohistochemistry, polymerase chain reaction for antigen receptor rearrangement or both were frequently required for definitive diagnosis. Two dogs had resection of an intestinal mass, and all dogs were treated with chemotherapy; chlorambucil and prednisone were most commonly prescribed. Overall response rate was 70%, and median survival time was 424 days (95% confidence interval: 105 to 1206 days). CLINICAL SIGNIFICANCE: Low-grade gastrointestinal lymphoma appears to be a rare condition in dogs, and treatment with chemotherapy results in a high response rate and favourable survival times. Further study is needed to determine its prevalence in dogs with chronic enteropathies.

Histiocytic sarcoma in 14 miniature schnauzers - a new breed predisposition?

OBJECTIVES: To describe a series of miniature schnauzers diagnosed with histiocytic sarcoma and assess for possible breed predisposition. MATERIALS AND METHODS: Medical records of miniature schnauzers with a diagnosis of histiocytic sarcoma between January 2008 and April 2015 were reviewed. Data collected included signalment, body weight, presenting complaint, date of diagnosis, clinicopathologic and diagnostic imaging findings, treatment, therapeutic response, date of death or last follow-up and necropsy findings. Breed predisposition was assessed with odds ratios, using breed-matched dogs without histiocytic sarcoma admitted during the study period as controls. Pedigree analysis was performed for dogs with available registration information. RESULTS: Fourteen miniature schnauzers were diagnosed with histiocytic sarcoma during the study period, making them over-represented among the hospital population (odds ratio=4·8, P=0·0009). Disease was considered localised in ten dogs and disseminated in four. Of the dogs with localised disease, nine were diagnosed with primary pulmonary histiocytic sarcoma based on the presence of a large pulmonary mass with (n=7) or without (n=2) evidence of intra-thoracic metastasis, and one had gastric histiocytic sarcoma with nodal metastasis. Treatments varied, but an aggressive clinical course was found in most patients. Pedigree analysis revealed a recent common ancestor for a subset of the dogs assessed. CLINICAL SIGNIFICANCE: Miniature schnauzers were over-represented among dogs with histiocytic sarcoma in this patient population. Pedigree analysis supports an inherited risk factor, which has not previously been suggested in the breed. Primary pulmonary involvement with or without intra-thoracic metastasis was common in this cohort.

Randomized Evaluation of the Effects of Anacetrapib through Lipid-modification (REVEAL)-A large-scale, randomized, placebo-controlled trial of the clinical effects of anacetrapib among people with established vascular disease: Trial design, recruitment, and baseline characteristics.

Patients with prior vascular disease remain at high risk for cardiovascular events despite intensive statin-based treatment. Inhibition of cholesteryl ester transfer protein by anacetrapib reduces low-density lipoprotein (LDL) cholesterol by around 25% to 40% and more than doubles high-density lipoprotein (HDL) cholesterol. However, it is not known if these apparently favorable lipid changes translate into reductions in cardiovascular events. METHODS: The REVEAL study is a randomized, double-blind, placebo-controlled clinical trial that is assessing the efficacy and safety of adding anacetrapib to effective LDL-lowering treatment with atorvastatin for an average of at least 4years among patients with preexisting atherosclerotic vascular disease. The primary assessment is an intention-to-treat comparison among all randomized participants of the effects of allocation to anacetrapib on major coronary events (defined as the occurrence of coronary death, myocardial infarction, or coronary revascularization). RESULTS: Between August 2011 and October 2013, 30,449 individuals in Europe, North America, and China were randomized to receive anacetrapib 100mg daily or matching placebo. Mean (SD) age was 67 (8) years, 84% were male, 88% had a history of coronary heart disease, 22% had cerebrovascular disease, and 37% had diabetes mellitus. At the randomization visit (after at least 8weeks on a protocol-defined atorvastatin regimen), mean plasma LDL cholesterol was 61 (15) mg/dL and HDL cholesterol was 40 (10) mg/dL. INTERPRETATION: The REVEAL trial will provide a robust evaluation of the clinical efficacy and safety of adding anacetrapib to an effective statin regimen. Results are anticipated in 2017.

Effects of empagliflozin on blood pressure and markers of arterial stiffness and vascular resistance in patients with type 2 diabetes.

AIMS: To determine the effects of empagliflozin on blood pressure (BP) and markers of arterial stiffness and vascular resistance in patients with type 2 diabetes mellitus (T2DM). METHODS: We conducted a post hoc analysis of data from a phase III trial in patients with T2DM and hypertension receiving 12 weeks' empagliflozin and four phase III trials in patients with T2DM receiving 24 weeks' empagliflozin (cohort 1, n = 823; cohort 2, n = 2477). BP was measured using 24-h BP monitoring (cohort 1) or seated office measurements (cohort 2). RESULTS: Empagliflozin reduced systolic BP (SBP) and diastolic BP in both cohorts (p < 0.001 vs placebo), without increasing heart rate. Empagliflozin reduced pulse pressure (PP; adjusted mean difference vs placebo cohort 1: -2.3 mmHg; cohort 2: -2.3 mmHg), mean arterial pressure (MAP; cohort 1, -2.3 mmHg; cohort 2, -2.1 mmHg) and double product (cohort 1, -385 mmHg × bpm; cohort 2, -369 mmHg × bpm) all p < 0.001 vs placebo. There was a trend towards a reduction in the ambulatory arterial stiffness index (AASI) with empagliflozin in cohort 1 (p = 0.059 vs placebo). AASI was not measured in cohort 2. Subgroup analyses showed that there were greater reductions in PP with increasing baseline SBP in cohort 1 (p = 0.092). In cohort 2, greater reductions in MAP were achieved in patients with higher baseline SBP (p = 0.027) and greater reductions in PP were observed in older patients (p = 0.011). CONCLUSIONS: Empagliflozin reduced BP and had favourable effects on markers of arterial stiffness and vascular resistance.

The effects of proton pump inhibition on patient-reported severity of dyspepsia when receiving dual anti-platelet therapy with clopidogrel and low-dose aspirin: analysis from the Clopidogrel and the Optimization of Gastrointestinal Events Trial.

BACKGROUND: Dual anti-platelet therapy with clopidogrel and low-dose aspirin increases the risk for gastrointestinal clinical events. Omeprazole has been shown to significantly reduce these events without compromising cardiovascular safety in patients treated with dual anti-platelet therapy. Whether or not omeprazole improves patient-reported outcomes is undetermined. AIM: To assess the impact of prophylactic omeprazole with background dual anti-platelet therapy on patient-reported symptoms of dyspepsia compared to placebo. METHODS: We analysed results of the Severity of Dyspepsia Assessment questionnaires collected in the Clopidogrel and the Optimization of Gastrointestinal Events Trial. RESULTS: Patient-reported outcome data from 3759 subjects were available for analysis. At 4 weeks, the mean scores of pain intensity and nonpain symptoms were lower in the omeprazole group (5.61 ± 0.17 vs. 6.40 ± 0.17, P = 0.001, and 10.61 ± 0.07 vs. 11.00 ± 0.07, P < 0.001 respectively). These differences were maintained at 24 weeks (5.91 ± 0.35 vs. 7.10 ± 0.37, P = 0.020 for pain intensity; 10.36 ± 0.12 vs. 10.93 ± 0.13, P = 0.001 for nonpain symptoms). After adjusting for covariates there were no statistically significant differences between the groups in the percent of patients with dyspepsia during follow-up. CONCLUSIONS: In addition to reducing the risk of gastrointestinal bleeding, statistically significant benefits with prophylactic omeprazole use on both pain and nonpain symptoms were evident at 4 weeks and sustained through 24 weeks. The clinical significance of these overall results is unclear, but greater in patients with pain at baseline.

Evaluation of a combination chemotherapy protocol including lomustine and doxorubicin in canine histiocytic sarcoma.

OBJECTIVES: To describe a chemotherapy protocol combining lomustine and doxorubicin in canine histiocytic sarcoma, including outcomes and toxicity. MATERIALS AND METHODS: Retrospective review of case records for dogs with histiocytic sarcoma treated with lomustine and doxorubicin (± cyclophosphamide) alternating every 2 weeks. Data collected included signalment, clinical signs, clinicopathological abnormalities, extent of disease, response, toxicity, time to tumour progression and survival time. RESULTS: Of 17 dogs, 15 had disseminated or metastatic disease. The median number of chemotherapy cycles (one dose of each drug) received was three; most dogs discontinued therapy due to progressive disease. Dose reductions or delays occurred in 18% of cycles. The overall response rate was 58%, with a median time to tumour progression of 185 (range, 59 to 268) days for responders. The overall median survival time was 185 (18 to 402) days. No significant prognostic factors were identified. CLINICAL SIGNIFICANCE: The protocol appeared well-tolerated, had some efficacy against canine histiocytic sarcoma in the study population and could be considered as an alternative to single-agent protocols; prospective comparison may be warranted.

Genetic risk, coronary heart disease events, and the clinical benefit of statin therapy: an analysis of primary and secondary prevention trials.

BACKGROUND: Genetic variants have been associated with the risk of coronary heart disease. In this study, we tested whether or not a composite of these variants could ascertain the risk of both incident and recurrent coronary heart disease events and identify those individuals who derive greater clinical benefit from statin therapy. METHODS: A community-based cohort study (the Malmo Diet and Cancer Study) and four randomised controlled trials of both primary prevention (JUPITER and ASCOT) and secondary prevention (CARE and PROVE IT-TIMI 22) with statin therapy, comprising a total of 48,421 individuals and 3477 events, were included in these analyses. We studied the association of a genetic risk score based on 27 genetic variants with incident or recurrent coronary heart disease, adjusting for traditional clinical risk factors. We then investigated the relative and absolute risk reductions in coronary heart disease events with statin therapy stratified by genetic risk. We combined data from the different studies using a meta-analysis. FINDINGS: When individuals were divided into low (quintile 1), intermediate (quintiles 2-4), and high (quintile 5) genetic risk categories, a significant gradient in risk for incident or recurrent coronary heart disease was shown. Compared with the low genetic risk category, the multivariable-adjusted hazard ratio for coronary heart disease for the intermediate genetic risk category was 1·34 (95% CI 1·22-1·47, p<0·0001) and that for the high genetic risk category was 1·72 (1·55-1·92, p<0·0001). In terms of the benefit of statin therapy in the four randomised trials, we noted a significant gradient (p=0·0277) of increasing relative risk reductions across the low (13%), intermediate (29%), and high (48%) genetic risk categories. Similarly, we noted greater absolute risk reductions in those individuals in higher genetic risk categories (p=0·0101), resulting in a roughly threefold decrease in the number needed to treat to prevent one coronary heart disease event in the primary prevention trials. Specifically, in the primary prevention trials, the number needed to treat to prevent one such event in 10 years was 66 in people at low genetic risk, 42 in those at intermediate genetic risk, and 25 in those at high genetic risk in JUPITER, and 57, 47, and 20, respectively, in ASCOT. INTERPRETATION: A genetic risk score identified individuals at increased risk for both incident and recurrent coronary heart disease events. People with the highest burden of genetic risk derived the largest relative and absolute clinical benefit from statin therapy. FUNDING: National Institutes of Health.

Health economic analysis of ticagrelor in patients with acute coronary syndromes intended for non-invasive therapy.

OBJECTIVE: To investigate the cost effectiveness of ticagrelor versus clopidogrel in patients with acute coronary syndromes (ACS) in the Platelet Inhibition and Patient Outcomes (PLATO) study who were scheduled for non-invasive management. METHODS: A previously developed cost effectiveness model was used to estimate long-term costs and outcomes for patients scheduled for non-invasive management. Healthcare costs, event rates and health-related quality of life under treatment with either ticagrelor or clopidogrel over 12 months were estimated from the PLATO study. Long-term costs and health outcomes were estimated based on data from PLATO and published literature sources. To investigate the importance of different healthcare cost structures and life expectancy for the results, the analysis was carried out from the perspectives of the Swedish, UK, German and Brazilian public healthcare systems. RESULTS: Ticagrelor was associated with lifetime quality-adjusted life-year (QALY) gains of 0.17 in Sweden, 0.16 in the UK, 0.17 in Germany and 0.13 in Brazil compared with generic clopidogrel, with increased healthcare costs of €467, €551, €739 and €574, respectively. The cost per QALY gained with ticagrelor was €2747, €3395, €4419 and €4471 from a Swedish, UK, German and Brazilian public healthcare system perspective, respectively. Probabilistic sensitivity analyses indicated that the cost per QALY gained with ticagrelor was below conventional threshold values of cost effectiveness with a high probability. CONCLUSIONS: Treatment of patients with ACS scheduled for 12 months' non-invasive management with ticagrelor is associated with a cost per QALY gained below conventional threshold values of cost effectiveness compared with generic clopidogrel. TRIAL REGISTRATION NUMBER: NCT000391872.

Canine osteosarcoma cells exhibit resistance to aurora kinase inhibitors.

We evaluated the effect of Aurora kinase inhibitors AZD1152 and VX680 on canine osteosarcoma cells. Cytotoxicity was seen in all four cell lines; however, half-maximal inhibitory concentrations were significantly higher than in human leukaemia and canine lymphoma cells. AZD1152 reduced Aurora kinase B phosphorylation, indicating resistance was not because of failure of target recognition. Efflux mediated by ABCB1 and ABCG2 transporters is one known mechanism of resistance against these drugs and verapamil enhanced AZD1152-induced apoptosis; however, these transporters were only expressed by a small percentage of cells in each line and the effects of verapamil were modest, suggesting other mechanisms contribute to resistance. Our results indicate that canine osteosarcoma cells are resistant to Aurora kinase inhibitors and suggest that these compounds are unlikely to be useful as single agents for this disease. Further investigation of these resistance mechanisms and the potential utility of Aurora kinase inhibitors in multi-agent protocols is warranted.

Footprints of divergent selection in natural populations of Castanopsis fargesii (Fagaceae).

Given predicted rapid climate change, an understanding of how environmental factors affect genetic diversity in natural populations is important. Future selection pressures are inherently unpredictable, so forest management policies should maintain both overall diversity and identify genetic markers associated with the environmental factors expected to change most rapidly, like temperature and rainfall. In this study, we genotyped 648 individuals in 28 populations of Castanopsis fargesii (Fagaceae) using 32 expressed sequence tag (EST)-derived microsatellite markers. After removing six loci that departed from Hardy-Weinberg equilibrium, we measured genetic variation, population structure and identified candidate loci putatively under selection by temperature and precipitation. We found that C. fargesii populations possessed high genetic diversity and moderate differentiation among them, indicating predominant outcrossing and few restrictions to gene flow. These patterns reduce the possible impact of stochastic effects or the influence of genetic isolation. Clear footprints of divergent selection at four loci were discovered. Frequencies of five alleles at these loci were strongly correlated with environmental factors, particularly extremes in precipitation. These alleles varied from being near fixation at one end of the gradient to being completely absent at the other. Our study species is an important forest tree in the subtropical regions of China and could have a major role in future management and reforestation plans. Our results demonstrate that the gene flow is widespread and abundant in natural populations, maintaining high diversity, while diversifying selection is acting on specific genomic regions.

Clinical practice guideline: acute otitis externa executive summary.

The American Academy of Otolaryngology--Head and Neck Surgery Foundation (AAO-HNSF) has published a supplement to this issue featuring the updated Clinical Practice Guideline: Acute Otitis Externa, as a supplement to Otolaryngology-Head and Neck Surgery. To assist in implementing the guideline recommendations, this article summarizes the rationale, purpose, and key action statements. The 8 recommendations developed address appropriate diagnosis of acute otitis externa (AOE) and the use of oral and topical antimicrobials and highlight the need for adequate pain relief. An updated guideline is needed due to new clinical trials, new systematic reviews, and the lack of consumer participation in the initial guideline development group.

Clinical practice guideline: acute otitis externa.

OBJECTIVE: This clinical practice guideline is an update and replacement for an earlier guideline published in 2006 by the American Academy of Otolaryngology-Head and Neck Surgery Foundation. This update provides evidence-based recommendations to manage acute otitis externa (AOE), defined as diffuse inflammation of the external ear canal, which may also involve the pinna or tympanic membrane. The variations in management of AOE and the importance of accurate diagnosis suggest a need for updating the clinical practice guideline. The primary outcome considered in this guideline is clinical resolution of AOE. PURPOSE: The primary purpose of the original guideline was to promote appropriate use of oral and topical antimicrobials for AOE and to highlight the need for adequate pain relief. An updated guideline is needed because of new clinical trials, new systematic reviews, and the lack of consumer participation in the initial guideline development group. The target patient is aged 2 years or older with diffuse AOE. Differential diagnosis will be discussed, but recommendations for management will be limited to diffuse AOE, which is almost exclusively a bacterial infection. This guideline is intended for primary care and specialist clinicians, including otolaryngologists-head and neck surgeons, pediatricians, family physicians, emergency physicians, internists, nurse practitioners, and physician assistants. This guideline is applicable in any setting in which patients with diffuse AOE would be identified, monitored, or managed. ACTION STATEMENTS: The development group made strong recommendations that (1) clinicians should assess patients with AOE for pain and recommend analgesic treatment based on the severity of pain and (2) clinicians should not prescribe systemic antimicrobials as initial therapy for diffuse, uncomplicated AOE unless there is extension outside the ear canal or the presence of specific host factors that would indicate a need for systemic therapy. The development group made recommendations that (1) clinicians should distinguish diffuse AOE from other causes of otalgia, otorrhea, and inflammation of the external ear canal; (2) clinicians should assess the patient with diffuse AOE for factors that modify management (nonintact tympanic membrane, tympanostomy tube, diabetes, immunocompromised state, prior radiotherapy); (3) clinicians should prescribe topical preparations for initial therapy of diffuse, uncomplicated AOE; (4) clinicians should enhance the delivery of topical drops by informing the patient how to administer topical drops and by performing aural toilet, placing a wick, or both, when the ear canal is obstructed; (5) clinicians should prescribe a non-ototoxic preparation when the patient has a known or suspected perforation of the tympanic membrane, including a tympanostomy tube; and (6) clinicians should reassess the patient who fails to respond to the initial therapeutic option within 48 to 72 hours [corrected] to confirm the diagnosis of diffuse AOE and to exclude other causes of illness.

Ultrasound-guided fine needle aspiration in the diagnosis of thyroid nodules.

A retrospective study of 28 patients who underwent ultrasound-guided fine needle aspiration (FNA) biopsy for thyroid nodular disease was performed to assess the diagnostic accuracy of ultrasound-guided FNA biopsy in detecting malignancy of the thyroid. Sensitivity, specificity, positive predictive value, and negative predicative value were evaluated with respect to final histological surgical pathology. The study's results substantiate those of previous studies: when there is a negative ultrasound-guided FNA, there is high probability that the patient is free of thyroid malignancy and may be followed clinically without the need for surgery.