Anterior vestibule salvaging technique to limit silicone orbital implant extrusion following evisceration.

Purpose: The anterior vestibule salvaging ('Birdcage') technique may limit orbital implant extrusion following evisceration. Methods: A 10-year retrospective chart review from 2005 to 2015 of individuals who underwent evisceration procedures utilizing the vestibule salvaging technique was performed. Results: A total of 96 patients (61 male; 35 female; average age 64 years; range 17-96 years) underwent evisceration with a technique avoiding anterior scleral relaxing incisions. Three (3.1%) patients had documented extrusion of the silicone implant. Time from evisceration to extrusion ranged from 26 to 372 days. Conclusions: Maintenance of the anterior scleral vestibule during evisceration may decrease extrusion rates after surgery compared with traditional evisceration techniques that utilize anterior relaxing incisions.

The Candida albicans virulence factor candidalysin polymerizes in solution to form membrane pores and damage epithelial cells.

Candida albicans causes severe invasive candidiasis. C. albicans infection requires the virulence factor candidalysin (CL) which damages target cell membranes. However, the mechanism that CL uses to permeabilize membranes is unclear. We reveal that CL forms membrane pores using a unique mechanism. Unexpectedly, CL readily assembled into polymers in solution. We propose that the basic structural unit in polymer formation is a CL oligomer, which is sequentially added into a string configuration that can close into a loop. CL loops appear to spontaneously insert into the membrane to become pores. A CL mutation (G4W) inhibited the formation of polymers in solution and prevented pore formation in synthetic lipid systems. Epithelial cell studies showed that G4W CL failed to activate the danger response pathway, a hallmark of the pathogenic effect of CL. These results indicate that CL polymerization in solution is a necessary step for the damage of cellular membranes. Analysis of CL pores by atomic force microscopy revealed co-existence of simple depressions and more complex pores, which are likely formed by CL assembled in an alternate oligomer orientation. We propose that this structural rearrangement represents a maturation mechanism that stabilizes pore formation to achieve more robust cellular damage. To summarize, CL uses a previously unknown mechanism to damage membranes, whereby pre-assembly of CL loops in solution leads to formation of membrane pores. Our investigation not only unravels a new paradigm for the formation of membrane pores, but additionally identifies CL polymerization as a novel therapeutic target to treat candidiasis.

The fungus Candida albicans is the most common cause of yeast infections in humans. Like many other disease-causing microbes, it releases several virulent proteins that invade and damage human cells. This includes the peptide candidalysin which has been shown to be crucial for infection. Human cells are surrounded by a protective membrane that separates their interior from their external environment. Previous work showed that candidalysin damages the cell membrane to promote infection. However, how candidalysin does this remained unclear. Similar peptides and proteins cause harm by inserting themselves into the membrane and then grouping together to form a ring. This creates a hole, or 'pore', that weakens the membrane and allows other molecules into the cell's interior. Here, Russell, Schaefer et al. show that candidalysin uses a unique pore forming mechanism to impair the membrane of human cells. A combination of biophysical and cell biology techniques revealed that the peptide groups together to form a chain. This chain of candidalysin proteins then closes in on itself to create a loop structure that can insert into the membrane to form a pore. Once embedded within the membrane, the proteins within the loops rearrange again to make the pores more stable so they can cause greater damage. This type of pore formation has not been observed before, and may open up new avenues of research. For instance, researchers could use this information to develop inhibitors that stop candidalysin from forming chains and harming the membranes of cells. This could help treat the infections caused by C. albicans.

Effectiveness of antibiotics for acute sinusitis in real-life medical practice.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Determining bacterial aetiology of acute sinusitis is difficult without employing invasive procedures. Most episodes of acute sinusitis resolve spontaneously. Antibiotics have demonstrated efficacy for the treatment of acute bacterial sinusitis in clinical trials yet little is known of their effectiveness in real-life treatment settings. WHAT THIS STUDY ADDS: Most cases of untreated acute sinusitis resolved spontaneously. Antibiotics were more effective when given within the first 10 days of treatment. This had no effect on later recurrence. Patients with poor oro-dental condition or recent antibiotic use may derive the most benefit from an antibiotic prescription and this should be considered by prescribers. The antibiotics used were found to be equally effective. Existing recommendations to identify acute sinusitis with high probability of bacterial origin, such as the French recommendations, fever or duration of symptoms fail to identify patients in whom antibiotics are more effective. AIMS: To assess the effectiveness of antibiotics in acute bacterial sinusitis. METHODS: This was a prospective cohort study with 2 months follow-up of 5640 patients with acute sinusitis included by a random sample from 1174 GPs and 120 ENT specialists. Main outcomes were short-term initial success, defined as the absence of prescription of (another) antibiotic or sinus lavage within 10 days, and lack of recurrence between the 11th and 60th day, after initial success. RESULTS: Initial success was found in 88.7% (95% CI 85.1, 91.4%) of patients without antibiotic prescription at inclusion and 96.2% (95% CI 95.7, 96.7%) of patients prescribed antibiotics. The 10 day adjusted hazard ratio (HR) for treatment failure (new antibiotic prescription or sinus drainage) with initial antibiotics compared with no antibiotics was 0.30 (95% CI 0.21, 0.42) with no difference between antibiotics. Antibiotics were more effective in patients with poor oro-dental condition (HR 0.04, 95% CI 0.01, 0.20) and in patients who had already used antibiotics during the previous 2 months (HR 0.09, 95% CI 0.03, 0.28). For patients without failure at 10 days, recurrence between the 11th and 60th day was similar whether or not they had initially been prescribed an antibiotic, 94.1% (95% CI 93.4, 94.7%) and 93.4% (95%CI 90.3, 95.5%), respectively. CONCLUSION: Most acute sinusitis cases not prescribed antibiotics resolve spontaneously. Antibiotics reduced by 3.3-fold the risk of failure within 10 days, without impact on later recurrence. The greatest benefit of antibiotics was found for patients with poor oro-dental condition or with antibiotic use within the previous 2 months.

Concordance between prescriber- and patient-reported previous medical history and NSAID indication in the CADEUS cohort.

PURPOSE: Various data sources may be used in pharmacoepidemiological studies. When they cannot be obtained from valid databases, medical data must be obtained from physicians or patients. In the CADEUS study, both patients and their prescribers reported medical data allowing investigation of the concordance between these sources. METHODS: CADEUS is a French national cohort study of traditional non-steroidal anti-inflammatory drug (NSAID) and coxib users conducted between September 2003 and August 2004 in France that employed self-administered questionnaires to obtain medical data from patients and their prescribers. The Kappa statistic (kappa) was used to measure concordance between patients and prescribers in 18 530 pairs with regard to previous medical history and index NSAID indication. RESULTS: For previous medical history, the proportion of agreement ranged from 70.7 to 99.2% and concordance was: substantial (kappa = 0.61-0.80) for hypertension, myocardial infarction, stroke and diabetes; moderate (kappa = 0.41-0.60) for angina pectoris, peripheral arterial disease and hypercholesterolaemia; fair (kappa = 0.21-0.40) for unstable angina, cardiac insufficiency, dyspepsia, gastroesophageal reflux and gastric ulcer; slight (kappa < 0.21) for upper gastrointestinal haemorrhage. For index NSAID indication, the proportion of agreement ranged from 84.3 to 99.4% and concordance was almost perfect (kappa = 0.81-1.00) for inflammatory rheumatism, flu-like symptoms, dysmenorrhoea and dental pain; substantial for arthritis, back pain and headache; moderate for osteoarticular pain. CONCLUSIONS: Concordance was better for specific or serious conditions both regarding previous medical history and indication. Prescriber or patient perception and understanding may reduce concordance for certain items.

Diclofenac potassium 12.5mg tablets for mild to moderate pain and fever: a review of its pharmacology, clinical efficacy and safety.

Non-prescription (over-the-counter [OTC]) analgesics are used for the short-term treatment of acute painful conditions of mild to moderate intensity in everyday life. Well documented safety and efficacy, a rapid onset of action and a flexible daily dosing regimen are essential in this context. Film-coated, immediate-release, low-dose diclofenac potassium, developed for OTC use, offers a flexible daily dosing regimen with an initial dose of two tablets (2 x 12.5mg) followed by one or two tablets up to a maximum daily dose of six tablets (75 mg/day). The maximum plasma drug concentration is reached 30 minutes after administration, and the mean terminal half-life is 1-2 hours, allowing a 4- to 6-hour duration of activity, depending on the condition. Thirteen randomised, double-blind trials with both placebo and active controls have demonstrated the efficacy of diclofenac potassium 12.5mg tablets in conditions suitable for treatment with OTC medication, for example, acute lower back pain, headache, acute pain after dental extraction, symptoms of cold and influenza (including fever), and dysmenorrhoea. A single dose of diclofenac potassium 12.5mg is the lowest recommended effective dose. A two-tablet single dose of 25mg is at least as effective as ibuprofen 400mg. A flexible dosing regimen of an initial two tablets followed by one or two tablets up to a total daily dose of 75 mg is as effective as ibuprofen used in comparable fashion up to a total daily dose of 1200 mg. The incidence of adverse events in patients taking single or multiple doses of diclofenac potassium is similar to that of ibuprofen and placebo. In a safety study conducted to compare diclofenac potassium with ibuprofen for up to 3 months in patients with osteoarthritis of the knee, no differences in the pattern of adverse events were noted. There was no evidence of either hepatic injury or cardiovascular safety-related issues at any time during the study. Patients are generally capable of taking diclofenac potassium appropriately. A maximum OTC treatment duration of 5 days for pain and 3 days for fever is recommended.

Suffer the little children: fixed intraoral habit appliances for treating childhood thumbsucking habits: a critical review of the literature.

A critical review of the literature is presented covering the treatment of childhood thumbsucking habits using fixed intraoral habit appliances (hayrake, palatal crib). The habit appliances are classified into type and function. Data is tabulated for key references revealing the fragmented and distorted nature of the literature and its lack of consistency. A chronological approach is presented to confirm the confused and idiosyncratic character of the literature. Information is provided on the early work of Massler and Graber and the paradox of Mack, Korner and Reider. Haryett's seminal studies at the University of Alberta regarding aspects of the treatment used are critically reviewed. Reflections are presented on why Larsson's study, casting doubt on the wisdom of using habit appliances, continues to be ignored. The emergence of the Bluegrass Appliance is discussed in terms of its being a more humane appliance and the seeming reluctance of practitioners to apply it as a kinder form of appliance therapy. Information is reported on the pain and serious injuries inflicted on children by habit appliances. A comparison of the use of appliances in the USA is made with the UK, where fixed habit appliances are not popular. Concludes that fixed intraoral habit appliances are cruel and inflict pain and suffering on children out of all proportion to their necessity. Questions why these appliances continue to be used, implying that it could be a combination of financial inducement, professional insularity and the absence of concerted opposition from behavioural therapists.