Preservation or removal of the lateral nasal wall in endoscopic management of maxillary sinus neoplasia: A comparison of approach related morbidity.

BACKGROUND: The endoscopic modified medial maxillectomy (MMM) and prelacrimal approach (PLA) are two routinely performed endoscopic approaches to the maxillary sinus when access via a middle meatal antrostomy is insufficient. However, there is no data in the literature that has compared outcomes and complication profile between the two procedures to determine which approach is superior. OBJECTIVE: To compare the approach related morbidity of PLA and MMM. METHODS: A retrospective cohort study of all consecutive adult patients undergoing either MMM or PLA from 2009 to 2023 were identified. The primary outcome was development of epistaxis, paraesthesia, lacrimal injury, iatrogenic sinus dysfunction within a minimum of 3 months post-operative follow up. RESULTS: 39 patients (44 sides) underwent PLA and 96 (96 sides) underwent MMM. There were no statistically significant differences between the rates of paraesthesia (9.1 % vs 14.6 %, p = 0.367) or prolonged paraesthesia (2.3 % vs 5.2 %, p = 0.426), iatrogenic maxillary sinus dysfunction (2.3 % vs 5.2 %, p = 0.426) or adhesions requiring removal (4.5 % vs 4.2 %, p = 0.918). No cases of epiphora or nasal cavity stenosis occurred in either arm in our study. CONCLUSIONS: According to our data, the endoscopic modified medial maxillectomy and prelacrimal approach are both equally safe approaches with their own benefits to access.

Case series: Lymphoid neoplasia in three elasmobranch species.

Elasmobranchs (sharks and rays) are charismatic cartilaginous fish, popular in public aquaria. Almost 200 shark and ray species are listed as threatened by the International Union for Conservation of Nature (IUCN), demonstrating the importance of captive breeding and research programmes. Limited studies investigate diseases of elasmobranchs in captive and free-living environments, and among available literature neoplasia is rarely reported, with even fewer cases of lymphoid neoplasia documented. This article outlines the first reports of lymphoid neoplasia in three elasmobranch species in which haematopoietic neoplasms have not been reported to date. It summarizes signalment, history and histopathologic findings in an undulate ray, Raja undulata (Lacepede), a common smooth-hound, Mustelus mustelus (Linnaeus) and a bat ray, Myliobatis californica (Gill). Lesions were confirmed in a wide range of tissues and evidence of lymphoid leukaemia was seen in two cases. This small-scale review demonstrates that lymphoid neoplasia should be considered as a differential diagnosis in elasmobranchs presenting with lethargy and anorexia and highlights the challenges of immunohistochemical work up.

Recreating the microscopic direct access Draf 2a frontal sinusotomy in the endoscopic era and comparison to an angled instrument approach.

PURPOSE: Microscopic Draf 2a frontal sinusotomy relied on direct access. However, the modern-day endoscopic approach is hindered by the anterior-posterior dimensions of the frontal recess. The nasofrontal beak, angled endoscopes, and variable frontal recess anatomy make the surgery challenging. Carolyn's window frontal sinusotomy removes the limitation of anterior-posterior dimensions and is an endoscopic version of the microscopic Draf 2a. This study aims to compare the perioperative outcomes and morbidity from endoscopic direct access Draf 2a compared to angled access Draf 2a. METHODS: Consecutive adult patients (> 18 years) seen at a tertiary referral clinic who underwent Draf 2a frontal sinus surgery using either endoscopic direct access (Carolyn's window) or endoscopic angled instrumentation were included. Patients who underwent Carolyn's window were compared to those with angled Draf 2a frontal sinusotomy. RESULTS: One hundred patients (age 51.96 ± 15.85 years, 48.0% female, follow-up 60.75 ± 17.34 months) were included. 44% of patients used Carolyn's window approach. 100% [95% CI 98.2-100%] of patients achieved successful frontal sinus patency. Both groups were comparable for early morbidities (bleeding, pain, crusting, and adhesions) and late morbidities (retained frontal recess partitions). There were no other morbidities in the early and late postoperative periods. CONCLUSION: The endoscopic direct access Draf 2a, or Carolyn's window, removes the anteroposterior diameter limitation. The frontal sinus patency and early and late surgical morbidities of direct access Draf 2a were comparable with the angled Draf 2a frontal sinusotomy. Surgical modifications, often with drills and bone removal, can be successfully made to enhance access in endoscopic sinus surgery without concern for additional morbidity.

Overall survival and prognostic factors in diabetic patients with invasive fungal rhinosinusitis.

BACKGROUND: Patients with diabetes mellitus (DM) are susceptible to invasive fungal rhinosinusitis (IFRS). The mortality rate of IFRS varies greatly among the patients with DM. OBJECTIVE: To identify the prognostic factors for the overall survival of patients with DM and IFRS. METHODS: A retrospective study was conducted in four tertiary hospitals in Thailand, Malaysia and Myanmar. Patients diagnosed with IFRS and DM from 2008 to 2019 were identified. The outcome was the overall survival. Variables analyzed for risk factors were age, HbA1C level, ketoacidosis, white blood cell count, hyperglycemia, duration of DM, current use of diabetic medications, serum creatinine level, and the extensions of IFRS to the orbit, the cavernous sinus and intracranial cavity. RESULTS: Sixty-five diabetic patients with IFRS (age 57.9 ± 13.4 years, male 60%) were identified. The mortality rate was 21.5%. The extensions of IFRS to the cavernous sinus (hazard ratio 5.1, 95% CI [1.4-18.2], p = 0.01) and intracranial cavity (hazard ratio 3.4, 95% CI [1.1-11.3, p = 0.05) predicted mortality. Current use of diabetic medications decreased the mortality risk (hazard ratio 0.2, 95% CI [0.1-0.9], p = 0.03). The 6-month overall survival of the patients with and without the cavernous sinus extension were 51.4% and 83.6%, (p = 0.001), with and without intracranial extension 53.3% and 88.9%, (p = 0.001), and with and without current diabetic medications 82.3% and 57.5%, respectively (p = 0.045). CONCLUSIONS: The extensions of IFRS to the cavernous sinus and intracranial cavity increased the risk of death in patients with DM. Survival was primarily related to current use of diabetic medications.

Mepolizumab decreases tissue eosinophils while increasing type-2 cytokines in eosinophilic chronic rhinosinusitis.

BACKGROUND: Eosinophilic chronic rhinosinusitis is an often treatment-resistant inflammatory disease mediated by type-2 cytokines, including interleukin (IL)-5. Mepolizumab, a monoclonal antibody drug targeting IL-5, has demonstrated efficacy and safety in inflammatory airway disease, but there is negligible evidence on direct tissue response. The study's aim was to determine the local effect of mepolizumab on inflammatory biomarkers in sinonasal tissue of eosinophilic chronic rhinosinusitis patients. METHODS: Adult patients with eosinophilic chronic rhinosinusitis received 100mg mepolizumab subcutaneously at four-weekly intervals for 24 weeks in this prospective phase 2 clinical trial. Tissue eosinophil counts, eosinophil degranulation (assessed as submucosal eosinophil peroxidase deposition by immunohistochemistry) and cytokine levels (measured in homogenates by immunoassay) were evaluated in ethmoid sinus tissue biopsies collected at baseline and at weeks 4, 8, 16 and 24. RESULTS: Twenty patients (47.7 ± 11.7 years, 50% female) were included. Sinonasal tissue eosinophil counts decreased after 24 weeks of treatment with mepolizumab (101.64 ± 93.80 vs 41.74 ± 53.76 cells per 0.1 mm2 ; p = .035), eosinophil degranulation remained unchanged (5.79 ± 2.08 vs 6.07 ± 1.20, p = .662), and type-2 cytokine levels increased in sinonasal tissue for IL-5 (10.84 ± 18.65 vs 63.98 ± 50.66, p = .001), IL-4 (4.48 ± 3.77 vs 9.38 ± 7.56, p = .004), IL-13 (4.02 ± 2.57 vs 6.46 ± 3.99, p = .024) and GM-CSF (1.51 ± 1.74 vs 4.50 ± 2.97, p = .001). CONCLUSION: Mepolizumab reduced eosinophils in sinonasal tissue, demonstrating that antagonism of IL-5 suppresses eosinophil trafficking. With reduced tissue eosinophils, a local type-2 inflammatory feedback loop may occur. The study exposes mechanistic factors which may explain incomplete treatment response.

Effect of monoclonal antibody drug therapy on mucosal biomarkers in airway disease: A systematic review.

BACKGROUND: Monoclonal antibody therapies have a growing role in treating refractory airway disease. OBJECTIVE: The review aimed to summarize the response of respiratory mucosa to monoclonal antibody treatments in inflammatory airway conditions. DESIGN: We conducted a systematic review including risk of bias assessment. DATA SOURCES: MEDLINE, EMBASE and PubMed from 1 January 2000 to 16 November 2019 were searched. ELIGIBILITY CRITERIA: Eligible studies assessed the immunological and histological response of airway mucosa to monoclonal antibody therapy compared with baseline or a comparison group in patients with respiratory diseases (asthma, chronic rhinosinusitis and allergic rhinitis). Any prospective interventional studies, including randomized controlled trials (RCTs) and single-arm trials, were eligible. RESULTS: There were 4195 articles screened, and full-text analysis produced n = 11 studies with extractable data. Nine were RCTs, and two were single-arm trials. These studies focused on asthma (n = 9 articles), chronic rhinosinusitis (n = 1) and allergic rhinitis (n = 1). Five monoclonal antibody drugs were assessed (omalizumab, mepolizumab, dupilumab, benralizumab and tralokinumab). Risk of bias was low (n = 6) or unclear (n = 3) in the RCTs and moderate in the single-arm trials. Omalizumab reduced the mucosal concentration of its target, IgE. Dupilumab reduced the concentration of one of its targets, IL-13, but not IL-4. Omalizumab, mepolizumab and benralizumab reduced tissue eosinophil cell density. Dupilumab decreased mucosal eosinophil granule proteins. Tralokinumab did not affect airway mucosa. CONCLUSIONS: Knowledge of the expected biological response of monoclonal antibody therapy on biomarkers in disease tissue provides an important supplement to data about clinical outcomes. An understanding of the biological effect is essential to identify likely responders, reasons for treatment failure and necessary adjustments to monoclonal antibody treatment. Further investigation into the effect of monoclonal antibody therapy on disease mucosa and more precise endotyping are required to move closer to achieving personalized medicine.

The international sinonasal microbiome study: A multicentre, multinational characterization of sinonasal bacterial ecology.

The sinonasal microbiome remains poorly defined, with our current knowledge based on a few cohort studies whose findings are inconsistent. Furthermore, the variability of the sinus microbiome across geographical divides remains unexplored. We characterize the sinonasal microbiome and its geographical variations in both health and disease using 16S rRNA gene sequencing of 410 individuals from across the world. Although the sinus microbial ecology is highly variable between individuals, we identify a core microbiome comprised of Corynebacterium, Staphylococcus, Streptococcus, Haemophilus and Moraxella species in both healthy and chronic rhinosinusitis (CRS) cohorts. Corynebacterium (mean relative abundance = 44.02%) and Staphylococcus (mean relative abundance = 27.34%) appear particularly dominant in the majority of patients sampled. Amongst patients suffering from CRS with nasal polyps, a statistically significant reduction in relative abundance of Corynebacterium (40.29% vs 50.43%; P = .02) was identified. Despite some measured differences in microbiome composition and diversity between some of the participating centres in our cohort, these differences would not alter the general pattern of core organisms described. Nevertheless, atypical or unusual organisms reported in short-read amplicon sequencing studies and that are not part of the core microbiome should be interpreted with caution. The delineation of the sinonasal microbiome and standardized methodology described within our study will enable further characterization and translational application of the sinus microbiota.

Outcomes of pituitary surgery for Cushing's disease: a systematic review and meta-analysis.

PURPOSE: Transsphenoidal surgery (TSS) is the first-line treatment for Cushing's disease (CD). This review aimed to synthesize the remission and recurrence rates following TSS for CD and identify predictors of these outcomes. METHODS: Medline (1946-) and Embase (1947-) were searched until 23rd January 2019 for original studies. A meta-analysis was performed of remission and recurrence rates. Studies were excluded if patients had prior radiosurgery/radiotherapy, mixed pathologies or interventions without separated data, follow-up not reported or population size < 20. For recurrence rate syntheses, studies with follow-up < 6 months were excluded. RESULTS: The search produced 2663 studies, of which n = 68 were included, involving 5664 patients. Remission rates after primary and revision TSS were 80% [77-82] and 58% [50-66] at last follow-up. After primary TSS, predictors of remission were micro- v macroadenomas (83% v 68%, p < 0.01), imaging-visible adenomas (81% v 69%, p < 0.01), adenomas confirmed on histopathology (87% v 45%, p < 0.01), absence of cavernous sinus invasion (80% v 30%, p < 0.01), postoperative serum cortisol (MSeC) nadir < 2 µg/dL (< 55 nmol/L; 95% v 46%, p < 0.01) and lower preoperative 24-h urine free cortisol (1250 nmol v 1726 nmol, p < 0.01). For revision TSS, predictors of remission were postoperative MSeC nadir < 2 µg/dL (< 55 nmol/L; 100% v 38%, p < 0.01) and operations for recurrence v persistence (80% v 54%, p < 0.01). Recurrence rates after primary and revision TSS were 18% [14-22] and 28% [16-42]. CONCLUSIONS: TSS is most effective in primary microadenomas, visible on preoperative imaging and without CS invasion, lower preoperative 24-h urine free cortisol and postoperative MSeC nadir < 2 µg/dL (< 55 nmol/L).

Fungal ball of the maxillary sinus and the risk of persistent sinus dysfunction after simple antrostomy.

BACKGROUND: Maxillary sinus fungal ball is a common cause of unilateral maxillary sinusitis. Fungal balls or mycetomas are primarily treated with surgery to remove the fungus. However, this assumes the pre-fungal ball sinus cavity was normal and post-surgery patients may suffer from mucostasis in the sinus cavity with persistent symptoms. It is proposed that fungal balls are potentially a feature of impaired mucus clearance as they are a pathology in their own right. METHODS: A case series of consecutive patients undergoing antrostomy for maxillary sinus fungal ball was performed. Patient factors including age, gender, smoking status, comorbidities (allergy, asthma, and reflux), disease specific factors including duration of symptoms, microbiology (bacterial co-infection, Gram-positive and/or Gram-negative) and preoperative radiologic findings (extent of sinus development, and neo-osteogenesis/bone thickness) were collected. The primary outcome was sinus function defined by evidence of a normal functioning maxillary sinus, with the absence of mucostasis or pooling, on endoscopic exam at three months, six months and last follow-up. Endoscopic evaluation of inflammation was also collected. RESULTS: 28 patients (age 58.5 ± 15.5 years, 64.3% female) were assessed. Mucostasis was present at three months in 39.3%, at six months in 32.1%, and 17.9% at last follow-up. There was no comorbidity or radiologic finding that was associated with failure to normalize. Those patients with mucostasis had a higher modified Lund-Mackay endoscopic score at last follow-up (5.0 ± 0.7 v 0.2 ± 0.6, p < 0.01). CONCLUSIONS: Long term post-operative mucostasis occurred in 17.9% of patients following an adequate maxillary antrostomy for treatment of a fungal ball. Patients with mucostasis had persistent mucosal inflammation and a greater need for further surgery (modified medial maxillectomy).

Turbinate loss from non-inflammatory sinonasal surgery does not correlate with poor sinonasal function.

OBJECTIVE: The impact of turbinate resection on nasal function remains a controversial topic. In surgery for inflammatory sinonasal disease, turbinate resection is often avoided. In contrast, turbinate tissue is routinely sacrificed in endoscopic tumor and skull base surgery to achieve negative margins or gain adequate exposure. Anecdotally, these patients experience good self-reported post-operative nasal function despite extensive turbinate tissue loss. This study investigates the impact of turbinate resection on self-reported sinonasal function following endoscopic tumor or skull base surgery. STUDY DESIGN: Retrospective case series. SETTING: Tertiary Australian Hospitals. SUBJECTS AND METHODS: A retrospective review was performed on consecutive post-surgical patients after management for non-inflammatory sinus disease such as tumor resection or endoscopic skull base reconstruction. Outcome variables assessed included a 6-point Likert score for nasal obstruction, a 13-point Likert score for global nasal function and a 5-question sleep score. The degree of turbinate tissue loss (0-4) was determined by the number of inferior or middle turbinate subtotal resections. Regression analysis was performed, accounting for the effect of relevant demographic variables (smoking; asthma; allergic status; gastroesophageal reflux; malignancy; vestibule mucositis) and treatment variables (subtotal septectomy; Draf III; nasal radiotherapy.) RESULTS: 294 patients (age 52.9 ±â€¯17.6 years, 51.0% female) were assessed. Number of turbinates resected was not associated with poorer nasal obstruction score, global nasal function score or sleep score (OR = 1.77[0.93-3.38], OR = 0.60[0.33-1.12], B = 0.56[-1.58-2.69] respectively). Allergy and Draf3 were found to improve postoperative global nasal function score (OR = 2.07[1.04-4.13], P = 0.04, OR = 3.97[1.08-14.49], P = 0.04, respectively). CONCLUSION: In patients where surgery was performed for non-inflammatory sinus disease, turbinate resection is not correlated with poorer postoperative nasal obstruction, sinonasal function nor sleep quality.

Osteitis in Chronic Rhinosinusitis.

PURPOSE OF REVIEW: Osteitis is recognized as a common factor in recalcitrant chronic rhinosinusitis (CRS). There is evidence for the association of osteitis with revision surgeries and CRS severity, in terms of higher Lund-Mackay scores. This is a narrative review on the osteitis in CRS patients. RECENT FINDINGS: Evidence to date is inconclusive with regard to the etiology and pathogenesis of this bony thickening. Histopathology of osteitis in primary CRS is likely a process of neo-osteogenesis and bone remodeling. For better understanding, various associating factors have been studied including an inflammatory pattern of rhinosinusitis. Recent studies have associated osteitis with nasal polyps and tissue eosinophilia with the increase in periostin expression and P-glycoprotein mucosal expression. There is no association of osteitis to symptoms or quality of life. Osteitis is an outcome of neo-osteogenesis rather than inflammatory processes in CRS patients without a prior history of surgery. While CT has become a staple in osteitis assessment, the standards for grading osteitic severity remain in an experimental stage. There is no association between the presence or severity of osteitis at the time of surgery and clinical outcomes at 1 year after surgery. This review provides a comprehensive overview of the pathogenesis, epidemiology, and correlation with clinical and biological factors of osteitis in CRS patients.

Local specific Immunoglobulin E among patients with nonallergic rhinitis: a systematic review.

BACKGROUND: Allergen specific immunoglobulin can be present in the nasal mucosa of patients with non-allergic rhinitis (NAR). This condition is defined as local allergic rhinitis. However, the reported presence of nasal specific immunoglobulin E (nspIgE) among NAR is variable. The aim of this review was to summarize the studies which reported the presence of nspIgE among patients diagnosed as NAR. METHODS: Embase (1947- ) and Medline (1946-) were searched until 6th June 2017. A search strategy was utilized to identify studies on nspIgE among patients with NAR. The target population was patients with symptoms of rhinitis, but negative systemic allergen sensitization. Studies with original data on detectable nspIgE among the NAR population were included. Meta-analysis of single proportions as a weighted probability %(95%CI) was performed. Heterogeneity was explored amongst studies. RESULTS: A search strategy returned 2286 studies and 21 were included. These studies involved 648 participants with NAR. NspIgE was detected using either; 1. nasal secretions, 2. epithelial mucosa sampling, 3. tissue biopsies or 4. In-situ tests. Metaanalysis was performed on studies with nasal secretions. The weighted proportion of detectable nspIgE in nasal secretions within patients with NAR was 10.2 (7.4-13.4) %. Population definitions partly explained variability. Detection of nspIgE was lower in patients without a history suggestive of allergy compared to those with a positive allergic history (0 (0-3.1) % v 19.8 (14.5-25.6) %, p<0.01). CONCLUSION: NAR with positive allergy history suggests presence of nspIgE. These patients warrant further allergology evaluation to confirm localized nasal allergy, as they benefit from allergy therapy such as immunotherapy.

The current status of RANZCP CPD 2017 programme: a shift to regulation.

OBJECTIVE: This paper outlines the current status of the Royal Australian and New Zealand College of Psychiatrists' (RANZCP) Continuing Professional Development (CPD) programme, its main drivers and influences, and outlines potential future changes. CONCLUSIONS: The three features that appear to be essential for an effective CPD programme are the presence of high internal motivation for CPD participation, membership valuing workplace learning, and to ensure that the content for learning remains largely work-focused. The need to incorporate best learning evidence has witnessed the international trend to include peer, reflective and interactive learning tasks into the CPD programme. For this latter change to be successful, members need to be informed about the value of these new and different learning methodologies.

Methamphetamine use in patients presenting to emergency departments and psychiatric inpatient facilities: what are the service implications?

OBJECTIVES:: The aim of this study is to understand better the service implications of patients presenting to an inner city Australian Emergency Department (ED) and Acute Psychiatric Inpatient Service (AIS) with a history of recent crystal methamphetamine use. METHODS:: An audit was taken of all patients with recent crystal methamphetamine use presenting to St Vincent's Hospital Melbourne ED and AIS over the month of September 2017. Recorded information included patient demographics, diagnosis, aggressive episodes, restrictive interventions and other risk incidents. RESULTS:: Methamphetamine was related to 21.7% of AIS admissions. Of these individuals, half were involved in aggression towards staff. In the ED, 65.7% of patients with amphetamine use were aggressive to staff and 50% were aggressive towards other patients. There were high rates of physical (69.2%) and mechanical restraint (61.5%) in the ED setting. Methamphetamine use in the AIS was commonly associated with enduring psychotic disorders, whilst those managed exclusively in the ED were most commonly in an acute intoxicated state. CONCLUSIONS:: Methamphetamine use presents a significant challenge to EDs and acute mental health services. Additional resources are required to manage these patients and their impact on the health system needs to be factored into future service planning.

Donepezil for dementia due to Alzheimer's disease.

BACKGROUND: Alzheimer's disease is the most common cause of dementia in older people. One approach to symptomatic treatment of Alzheimer's disease is to enhance cholinergic neurotransmission in the brain by blocking the action of the enzyme responsible for the breakdown of the neurotransmitter acetylcholine. This can be done by a group of drugs known as cholinesterase inhibitors. Donepezil is a cholinesterase inhibitor.This review is an updated version of a review first published in 1998. OBJECTIVES: To assess the clinical efficacy and safety of donepezil in people with mild, moderate or severe dementia due to Alzheimer's disease; to compare the efficacy and safety of different doses of donepezil; and to assess the effect of donepezil on healthcare resource use and costs. SEARCH METHODS: We searched Cochrane Dementia and Cognitive Improvement's Specialized Register, MEDLINE, Embase, PsycINFO and a number of other sources on 20 May 2017 to ensure that the search was as comprehensive and up-to-date as possible. In addition, we contacted members of the Donepezil Study Group and Eisai Inc. SELECTION CRITERIA: We included all double-blind, randomised controlled trials in which treatment with donepezil was administered to people with mild, moderate or severe dementia due to Alzheimer's disease for 12 weeks or more and its effects compared with those of placebo in a parallel group of patients, or where two different doses of donepezil were compared. DATA COLLECTION AND ANALYSIS: One reviewer (JSB) extracted data on cognitive function, activities of daily living, behavioural symptoms, global clinical state, quality of life, adverse events, deaths and healthcare resource costs. Where appropriate and possible, we estimated pooled treatment effects. We used GRADE methods to assess the quality of the evidence for each outcome. MAIN RESULTS: Thirty studies involving 8257 participants met the inclusion criteria of the review, of which 28 studies reported results in sufficient detail for the meta-analyses. Most studies were of six months' duration or less. Only one small trial lasted 52 weeks. The studies tested mainly donepezil capsules at a dose of 5 mg/day or 10 mg/day. Two studies tested a slow-release oral formulation that delivered 23 mg/day. Participants in 21 studies had mild to moderate disease, in five studies moderate to severe, and in four severe disease. Seventeen studies were industry funded or sponsored, four studies were funded independently of industry and for nine studies there was no information on source of funding.Our main analysis compared the safety and efficacy of donepezil 10 mg/day with placebo at 24 to 26 weeks of treatment. Thirteen studies contributed data from 3396 participants to this analysis. Eleven of these studies were multicentre studies. Seven studies recruited patients with mild to moderate Alzheimer's disease, two with moderate to severe, and four with severe Alzheimer's disease, with a mean age of about 75 years. Almost all evidence was of moderate quality, downgraded due to study limitations.After 26 weeks of treatment, donepezil compared with placebo was associated with better outcomes for cognitive function measured with the Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog, range 0 to 70) (mean difference (MD) -2.67, 95% confidence interval (CI) -3.31 to -2.02, 1130 participants, 5 studies), the Mini-Mental State Examination (MMSE) score (MD 1.05, 95% CI 0.73 to 1.37, 1757 participants, 7 studies) and the Severe Impairment Battery (SIB, range 0 to 100) (MD 5.92, 95% CI 4.53 to 7.31, 1348 participants, 5 studies). Donepezil was also associated with better function measured with the Alzheimer's Disease Cooperative Study activities of daily living score for severe Alzheimer's disease (ADCS-ADL-sev) (MD 1.03, 95% CI 0.21 to 1.85, 733 participants, 3 studies). A higher proportion of participants treated with donepezil experienced improvement on the clinician-rated global impression of change scale (odds ratio (OR) 1.92, 95% CI 1.54 to 2.39, 1674 participants, 6 studies). There was no difference between donepezil and placebo for behavioural symptoms measured by the Neuropsychiatric Inventory (NPI) (MD -1.62, 95% CI -3.43 to 0.19, 1035 participants, 4 studies) or by the Behavioural Pathology in Alzheimer's Disease (BEHAVE-AD) scale (MD 0.4, 95% CI -1.28 to 2.08, 194 participants, 1 study). There was also no difference between donepezil and placebo for Quality of Life (QoL) (MD -2.79, 95% CI -8.15 to 2.56, 815 participants, 2 studies).Participants receiving donepezil were more likely to withdraw from the studies before the end of treatment (24% versus 20%, OR 1.25, 95% CI 1.05 to 1.50, 2846 participants, 12 studies) or to experience an adverse event during the studies (72% vs 65%, OR 1.59, 95% 1.31 to 1.95, 2500 participants, 10 studies).There was no evidence of a difference between donepezil and placebo for patient total healthcare resource utilisation.Three studies compared donepezil 10 mg/day to donepezil 5 mg/day over 26 weeks. The 5 mg dose was associated with slightly worse cognitive function on the ADAS-Cog, but not on the MMSE or SIB, with slightly better QoL and with fewer adverse events and withdrawals from treatment. Two studies compared donepezil 10 mg/day to donepezil 23 mg/day. There were no differences on efficacy outcomes, but fewer participants on 10 mg/day experienced adverse events or withdrew from treatment. AUTHORS' CONCLUSIONS: There is moderate-quality evidence that people with mild, moderate or severe dementia due to Alzheimer's disease treated for periods of 12 or 24 weeks with donepezil experience small benefits in cognitive function, activities of daily living and clinician-rated global clinical state. There is some evidence that use of donepezil is neither more nor less expensive compared with placebo when assessing total healthcare resource costs. Benefits on 23 mg/day were no greater than on 10 mg/day, and benefits on the 10 mg/day dose were marginally larger than on the 5 mg/day dose, but the rates of withdrawal and of adverse events before end of treatment were higher the higher the dose.

WITHDRAWN: Topical and systemic antifungal therapy for the symptomatic treatment of chronic rhinosinusitis.

BACKGROUND: Chronic rhinosinusitis (CRS) is an inflammatory disorder of the nose and sinuses. Since fungi were postulated as a potential cause of CRS in the late 1990s, there has been increasing controversy about the use of both topical and systemic antifungal agents in its management. Although interaction between the immune system and fungus has been demonstrated in CRS, this does not necessarily imply that fungi are the cause of CRS or that antifungals will be effective its management. OBJECTIVES: To assess the effectiveness of topical or systemic antifungal therapy in the treatment of CRS. SEARCH METHODS: We searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL); PubMed; EMBASE; CINAHL; Web of Science; BIOSIS Previews; Cambridge Scientific Abstracts; ICTRP and additional sources for published and unpublished trials. The date of the most recent search was 8 March 2011. SELECTION CRITERIA: All randomised, placebo-controlled trials considering the use of topical or systemic antifungal therapy in the treatment of CRS and allergic fungal sinusitis (AFS). CRS was defined using either the European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS) or American Academy of Otolaryngology - Head and Neck Surgery (AAO-HNS) criteria. DATA COLLECTION AND ANALYSIS: We reviewed the titles and abstracts of all studies obtained from the searches and selected trials that met the eligibility criteria. We extracted data using a pre-determined data extraction form. There was significant heterogeneity of outcome data reporting with reports containing both parametric and non-parametric representations of data for the same outcomes. Means and standard deviations for change data were unavailable for a number of trials. Due to the limited reported data, we contacted authors and used original data for data analysis. MAIN RESULTS: Six studies were included (380 participants). Five studies investigated topical antifungals and one study investigated systemic antifungals. The risk of bias in all included studies was low, with all trials being double-blinded and randomised. Pooled meta-analysis showed no statistically significant benefit of topical or systemic antifungals over placebo for any outcome. Symptom scores in fact statistically favoured the placebo group. Adverse event reporting was statistically significantly higher in the antifungal group. AUTHORS' CONCLUSIONS: On the basis of this meta-analysis, there is no evidence to support the use of either topical or systemic antifungal treatment in the management of CRS.

Utility of narrow band imaging in the diagnosis of middle turbinate head edema.

PURPOSE: Middle turbinate head edema has recently been found to have high specificity for diagnosis of inhalant allergy. However, subtle mucosal edema can be difficult to appreciate under white light endoscopy. Narrow band imaging (NBI) has the potential to demonstrate edema by identifying reduced mucosal vascularity and improve sensitivity for the detection of mucosal edema. Narrow band imaging was assessed to determine its utility in objectifying mucosal edema. MEATERIALS AND METHODS: A cross-sectional diagnostic study was performed on patients with edematous mucosa of the middle turbinate head. Under traditional white light endoscopy, areas of edematous mucosa were identified. Using NBI, these areas were compared to areas of normal mucosa on the middle turbinate head. NBI images of these same areas were then converted to grey scale and a vascularity index was created by pixel analysis and brightness in Fiji Image J software (Wisconsin, US). RESULTS: Thirty-three middle turbinates were assessed (age 42.4 ±â€¯12.5, 42.4% female). NBI discriminated between areas identified under white light endoscopy as edematous and normal (158.2 ±â€¯48.4 v 96.9 ±â€¯32.7 p < 0.01). Receiver operating curve (ROC) analysis suggested a threshold of 115 brightness units to define endoscopically visible edematous mucosa with sensitivity 70% and specificity 79% (ROC AUC, p = 0.85). CONCLUSIONS: NBI can differentiate edematous from normal mucosa. The potential for an objective measure of mucosal edema may assist research efforts and may provide a more sensitive tool for subtle mucosal inflammatory changes.

How to Assess, Control, and Manage Uncontrolled CRS/Nasal Polyp Patients.

PURPOSE OF REVIEW: Chronic rhinosinusitis (CRS) is a multidimensional inflammatory disorder of the nose and paranasal sinuses. We reviewed the recent literature to identify improved methods to assess, control, and manage these difficult to control patients. RECENT FINDINGS: The role of endotyping in CRS has offered a better understanding of the underlying pathophysiology and allows for more targeted treatment. The understanding of systemic disorders and their role in CRS and the importance of topical treatment reaching the sinuses has also allowed for better control of these patients. We have provided some of the commonly identified causes for uncontrolled CRS and a sensible approach to assessing these patients. We have also focused on common areas of pitfalls in the surgery and choice of patients and the role for ongoing systemic treatment. The future of managing this difficult condition includes endotyping using inflammatory markers and individualizing the treatment to the patient by using specific monoclonal antibodies.

The Role of Macrolides in Chronic Rhinosinusitis (CRSsNP and CRSwNP).

PURPOSE OF REVIEW: We assess the literature on the pharmacokinetics, indications, important considerations, and effectiveness of long-term, low-dose macrolide antibiotics in chronic rhinosinusitis (CRS). RECENT FINDINGS: The key to effective implementation of macrolide therapy in CRS is appropriate patient selection. Macrolides have demonstrated the most benefit in Th1-mediated non-eosinophilic CRS when used for durations of at least 3 months. Macrolide antibiotics have demonstrated great benefit when used for their anti-inflammatory or immunomodulatory properties, which include the blockage of pro-inflammatory cytokines, such as interleukin (IL)-8 and tumor necrosis factor-α (TNF-α). They have been used in CRS patients not responding to traditional corticosteroid-based treatment regimens, but appear to be most effective specifically in Th1-mediated non-eosinophilic CRS in long durations and low doses. Further research is needed to better identify characteristics known to correlate with macrolide response so early directed therapy can be implemented.

Determining position, velocity and acceleration of free-ranging animals with a low-cost unmanned aerial system.

Unmanned aerial systems (UASs), frequently referred to as 'drones', have become more common and affordable and are a promising tool for collecting data on free-ranging wild animals. We used a Phantom-2 UAS equipped with a gimbal-mounted camera to estimate position, velocity and acceleration of a subject on the ground moving through a grid of GPS surveyed ground control points (area ∼1200 m(2)). We validated the accuracy of the system against a dual frequency survey grade GPS system attached to the subject. When compared with GPS survey data, the estimations of position, velocity and acceleration had a root mean square error of 0.13 m, 0.11 m s(-1) and 2.31 m s(-2), respectively. The system can be used to collect locomotion and localisation data on multiple free-ranging animals simultaneously. It does not require specialist skills to operate, is easily transported to field locations, and is rapidly and easily deployed. It is therefore a useful addition to the range of methods available for field data collection on free-ranging animal locomotion.