WITHDRAWN: Interventions for ear discharge associated with grommets (ventilation tubes).

BACKGROUND: The insertion of grommets (also known as ventilation or tympanostomy tubes) is one of the most common surgical procedures performed on children. Postoperative otorrhoea (discharge) is the most common complication with a reported incidence ranging from 10% to 50%. In the UK, many ENT surgeons treat with topical antibiotics/steroid combinations, but general practitioners, mainly through fears of ototoxicity, are unlikely to prescribe these and choose systemic broad-spectrum antibiotics. OBJECTIVES: 1. To identify the most effective non-surgical management of discharge from ears with grommets in place.2. To identify the risks of non-surgical management for this condition (e.g. ototoxicity), and to set benefits of treatment against these risks. SEARCH METHODS: We searched the Cochrane Ear, Nose and Throat Disorders Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 1, 2005), MEDLINE (1966 to 2005) and EMBASE (1974 to 2005). We also searched the CINAHL, AMED, LILACS, ISI WEB OF KNOWLEDGE, ISI PROCEEDINGS, mRCT, NNR, ZETOC, KOREAMED, CSA, MEDCARIB, INDMED and SAMED databases. The date of the last search was February 2005. SELECTION CRITERIA: Randomised controlled trials of adults or children, with any type of grommet and an ear with discharge were included. The trials compared treatment with placebo or one treatment with another. The primary outcome measure was the duration of the discharge. DATA COLLECTION AND ANALYSIS: The trials were selected independently according to the above criteria by the four reviewers. Differences in opinion over the inclusion of studies were resolved by discussion. The studies were graded using the CASP critical appraisal tool. Analyses were based on the presence of discharge seven days from the onset of treatment. MAIN RESULTS: There was very little good quality evidence. Four studies were included, all of them investigating different interventions and therefore a meta-analysis was not possible.Only one study demonstrated a significant difference. Oral amoxicillin clavulanate was compared to placebo in 79 patients. The odds of having a discharge persisting eight days after starting treatment was 0.19 (95% CI 0.07 to 0.49) . The number needed to treat to achieve that benefit is 2.5. Participants in both arms of this study also received daily aural toilet. The results will therefore not be applicable to most settings including primary care. No significant benefit was shown in the two studies investigating steroids (oral prednisolone with oral amoxicillin clavulanate and topical dexamethasone with topical ciprofloxacin ear drops), or the one study comparing an antibiotic-steroid combination (Otosporin®) drops versus spray (Otomize®) (although more patients preferred the spray form). AUTHORS' CONCLUSIONS: The authors of this review have been unable to identify the most effective intervention or to assess the associated risks. Research is urgently needed into the effectiveness of oral versus topical antibiotics in this group of patients. Clinicians considering antibiotic treatment need to balance any potential benefit against the risks of side effects and antibiotic resistance.

Stoichiometries and affinities of interacting proteins from concentration series of solution scattering data: decomposition by least squares and quadratic optimization.

In studying interacting proteins, complementary insights are provided by analyzing both the association model (the stoichiometry and affinity constants of the intermediate and final complexes) and the quaternary structure of the resulting complexes. Many current methods for analyzing protein interactions either give a binary answer to the question of association and no information about quaternary structure or at best provide only part of the complete picture. Presented here is a method to extract both types of information from X-ray or neutron scattering data for a series of equilibrium mixtures containing the initial components at different concentrations. The method determines the association pathway and constants, along with the scattering curves of the individual members of the mixture, so as to best explain the scattering data for the mixtures. The derived curves then enable reconstruction of the intermediate and final complexes. Using simulated solution scattering data for four hetero-oligomeric complexes with different structures, molecular weights and association models, it is demonstrated that this method accurately determines the simulated association model and scattering profiles for the initial components and complexes. Recognizing that experimental mixtures contain static contaminants and nonspecific complexes with the lowest affinities (inter-particle interference) as well as the desired specific complex(es), a new analytical method is also employed to extend this approach to evaluating the association models and scattering curves in the presence of static contaminants, testing both a nonparticipating monomer and a large homo-oligomeric aggregate. It is demonstrated that the method is robust to both random noise and systematic noise from such contaminants, and the treatment of nonspecific complexes is discussed. Finally, it is shown that this method is applicable over a large range of weak association constants typical of specific but transient protein-protein complexes.

Reduction of venous thromboembolism (VTE) in hospitalized patients: aligning continuing education with interprofessional team-based quality improvement in an academic medical center.

PROBLEM: Despite clear prophylactic guidelines and national quality emphasis, a minority of hospitalized patients receive appropriate prophylaxis for venous thromboembolism (VTE). Data from the University of Kansas Hospital (KUH) revealed an unacceptably high incidence of VTE. APPROACH: The authors aligned continuing education with quality improvement through formation of an interprofessional, multidisciplinary team to develop strategic educational and system operational plans to decrease VTE incidence. The authors reviewed 261 charts with the secondary diagnosis of VTE for identification of themes or causes of VTE to develop multipronged educational and system-based action plans. The authors reviewed a "menu" of evidence-based content delivery techniques to develop the educational plan. Multiple noneducational adjunct system strategies were also developed and implemented. OUTCOMES: After implementation of all specific action plans, the KUH VTE incidence decreased 51% from November 2010 to June 2012 (from 12.68 to 6.10 per 1,000 patients). Insertion of peripherally inserted central catheters, a common identified theme, dropped from almost 360 insertions in December of 2010 to less than 200 insertions in April 2012. NEXT STEPS: Aligning continuing education with quality improvement through an interprofessional, multidisciplinary team approach was associated with a decrease in VTE. The authors describe challenges and lessons learned to inform implementation of similar quality-improvement-driven continuing education initiatives elsewhere. Challenges included time, resources, multiple service lines, and departments with variable acceptance of data. Lessons learned included the value of leadership commitment, interprofessional team work, assessing individual data, expertise of continuing education, using multiple educational methods, and the need for overall champions.

Quantifying emergency department admission rates for people with a learning disability.

No data is routinely collected by emergency departments (ED) in the UK to identify people who attend and who have a learning disability. This group have numerous additional needs in their healthcare management and a lack of support could be detrimental to their care. F800 codes from the International Classification of Diseases (ICD-10) that identify disorders of psychological development are often used to categorise specific disorders once admitted to hospital. Consequently, the F800 codes of patients who were admitted to hospital from Birmingham Heartlands Hospital ED for 1 year have been analysed to obtain some of this data. This study argues that, although only a small proportion of the admissions from this ED were by people with an F800 code, the exact numbers of attendances in many EDs remain unknown and the impact of their disabilities on their immediate care and the workload of the ED medical staff may be significant.

A report of the medical team activity at the 2009 Special Olympics GB.

OBJECTIVE: To quantify and categorise medical workload from the 2009 Special Olympics GB (SOL GB) which involved 2500 athletes with learning disabilities across 21 different sports supported by nearly 9000 family members, volunteers and staff over a 7-day period. DESIGN AND PARTICIPANTS: Prospective survey of all medical contacts that took place at the 2009 SOL GB with subsequent analysis of consultation rates, medical problems and medical activity. RESULTS: 581 medical consultations occurred during the 2009 SOL GB, with 95% of these for athletes. The majority of the athlete consultations were for musculoskeletal disorders, followed by skin wound care. Most athletes were judged fit to participate following their consultation. CONCLUSION: A large multisport event for athletes with learning disabilities carries a significant medical workload that has not been studied previously, with different sports having different individual risks and demands. The vast majority of consultations are for systemically well athletes that can be managed locally without necessity for hospital admission. This study identifies the quantity and nature of medical consultations undertaken during this event in an attempt to inform planning for future events.

Modulation of polyglutamine conformations and dimer formation by the N-terminus of huntingtin.

Polyglutamine expansions within different proteins are associated with nine different neurodegenerative diseases. There is growing interest in understanding the roles of flanking sequences from disease-relevant proteins in the intrinsic conformational and aggregation properties of polyglutamine. We report results from atomistic simulations and circular dichroism experiments that quantify the effect of the N-terminal 17-residue (Nt17) segment of the huntingtin protein on polyglutamine conformations and intermolecular interactions. We show that the Nt17 segment and polyglutamine domains become increasingly disordered as polyglutamine length (N) increases in Nt17-Q(N) constructs. Hydrophobic groups within Nt17 become sequestered in intramolecular interdomain interfaces. We also show that the Nt17 segment suppresses the intrinsic propensity of polyglutamine aggregation. This inhibition arises from the incipient micellar structures adopted by monomeric forms of the peptides with Nt17 segments. The degree of intermolecular association increases with increasing polyglutamine length and is governed mainly by associations between polyglutamine domains. Comparative analysis of intermolecular associations for different polyglutamine-containing constructs leads to clearer interpretations of recently published experimental data. Our results suggest a framework for fibril formation and identify roles for flanking sequences in the modulation of polyglutamine aggregation.

Analysis of self-associating proteins by singular value decomposition of solution scattering data.

We describe a method by which a single experiment can reveal both association model (pathway and constants) and low-resolution structures of a self-associating system. Small-angle scattering data are collected from solutions at a range of concentrations. These scattering data curves are mass-weighted linear combinations of the scattering from each oligomer. Singular value decomposition of the data yields a set of basis vectors from which the scattering curve for each oligomer is reconstructed using coefficients that depend on the association model. A search identifies the association pathway and constants that provide the best agreement between reconstructed and observed data. Using simulated data with realistic noise, our method finds the correct pathway and association constants. Depending on the simulation parameters, reconstructed curves for each oligomer differ from the ideal by 0.05-0.99% in median absolute relative deviation. The reconstructed scattering curves are fundamental to further analysis, including interatomic distance distribution calculation and low-resolution ab initio shape reconstruction of each oligomer in solution. This method can be applied to x-ray or neutron scattering data from small angles to moderate (or higher) resolution. Data can be taken under physiological conditions, or particular conditions (e.g., temperature) can be varied to extract fundamental association parameters (DeltaH(ass), DeltaS(ass)).