Hearing interventions to prevent dementia.

Hearing loss is a marker of risk for cognitive decline and dementia. Controlled hearing intervention studies of long-term cognitive outcomes are challenging, and thus the evidence for the impact of hearing interventions is primarily from observational studies and will likely continue to be from studies other than randomised controlled trials. Seven studies of hearing interventions with cognitive outcomes assessed over longer than 3 years are reviewed. Most were of low-to-moderate quality. One cochlear implant study had indeterminate findings. Of six hearing aid studies, three reported a positive impact of hearing aid use while three reported no impact of hearing aid use on cognitive decline or incident cognitive impairment. Further studies are required to elucidate the benefit of hearing interventions on long-term cognitive outcomes. Research should include objectively ascertained hearing data, theoretically motivated cognitive outcomes including dementia subtypes, characterisation, and control for confounds and application of advanced statistical modelling to test causal hypotheses.

Subannular tube insertion: anatomical considerations.

OBJECTIVES: To assess the distance between the bony groove created during subannular tubes placement and the chorda tympani, and examine the depth of the hypotympanum and retrotympanum. METHOD: Grooves drilled in cadaver temporal bones at two levels were imaged to measure: the distance between the chorda tympani nerve and the tympanic sulcus, and the depth of the hypotympanum and the retrotympanum relative to the annulus. RESULTS: The chorda tympani was between 0 and 5 mm from the groove cut across the annulus. The hypotympanum average depth was 2 mm (0.44-6.40 mm) and the retrotympanum average depth was 1 mm (0-2.53 mm). CONCLUSION: Grooves drilled across the tympanic sulcus should be placed at a point 20 per cent of the height of the tympanic membrane or lower; this will ensure least risk of injury to the chorda tympani nerve. The depth of the hypotympanum and retrotympanum dictates that the posteroinferior part of a subannular tube flange should be approximately 2 × 1 mm.

Sinonasal Lymphoma Presenting as a Probable Sanctuary Site for Relapsed B Acute Lymphoblastic Leukaemia: A Case Report and Review of the Literature.

Sinonasal lymphoma is a non-Hodgkin lymphoma (NHL) representing 1.5% of all lymphomas. It presents as an unremitting ulceration with progressive destruction of midline sinonasal and surrounding structures. Poor prognosis warrants early treatment although diagnosis is challenging and frequently delayed. It is usually primary in origin and to our knowledge the sinonasal region has never been reported as a sanctuary site in leukaemia/lymphoma relapse. We present a unique case of B-cell ALL (acute lymphoblastic leukaemia) with late relapse to the nasal septum as a sinonasal lymphoblastic lymphoma and with genetic support for this as a sanctuary site.

Adherence of Candida albicans to silicone is promoted by the human salivary protein SPLUNC2/PSP/BPIFA2.

Interactions between Candida albicans, saliva and saliva-coated oral surfaces are initial events in the colonization of the oral cavity by this commensal yeast, which can cause oral diseases such as candidiasis and denture stomatitis. Candida albicans also colonizes silicone voice prostheses, and the microbial biofilm formed can impair valve function, necessitating frequent prosthesis replacement. We have previously shown that saliva promoted binding of C. albicans cells to silicone in vitro, and that the selective binding of specific salivary proteins to voice prosthesis silicone mediated attachment of C. albicans cells. The C. albicans cells adhered to a polypeptide (or polypeptides) of ~36 kDa eluted from saliva-treated silicone. We show here that a protein of similar size was identified in replicate blots of the eluate from saliva-treated silicone when the blots were probed with antibodies to human SPLUNC2, a salivary protein with reported microbial agglutination properties. In addition, SPLUNC2 was depleted from saliva that had been incubated with silicone coupons. To determine whether SPLUNC2 is a yeast-binding protein, SPLUNC2 cDNA was expressed in Escherichia coli. Purified recombinant His-tagged protein (SPLUNC2r) bound to silicone as demonstrated by immunoblot analysis of an eluate from SPLUNC2r-treated silicone coupons and (35) S-radiolabelled C. albicans cells adhered in a dose-dependent manner to SPLUNC2r-coated silicone. We conclude that SPLUNC2 binds to silicone and acts as a receptor for C. albicans adherence to, and subsequent colonization of, voice prosthesis silicone.

The impact of a nurse-led chronic musculoskeletal pain clinic on healthcare utilization.

AIMS AND OBJECTIVES: To determine whether a nurse-led chronic musculoskeletal pain clinic for fibromyalgia patients can reduce utilization of healthcare services. BACKGROUND: People with fibromyalgia often consult multiple specialities due to the vast nature of their symptoms but receive little or no help in managing their symptoms. DESIGN: A retrospective evaluation of a nurse consultant-led chronic pain management clinic. METHODS: The frequency of hospital attendances in the five years before and three years after pain clinic attendance was evaluated. General practitioner (GP) attendances in the 12-month period before and after pain clinic attendance were compared with attendances for two groups of patients from an established GP cohort: (i) patients referred to rheumatology new patient clinics and (ii) all patients with fibromyalgia referred to any hospital new patient clinic. RESULTS: In the three years following attendance at the pain clinic, the mean number of hospital appointments fell significantly from 2.8 to 1.4 per annum (p < 0.001). The mean reduction seen in hospital clinic attendances in the first year (0.8/annum) improved in the second (1.2/annum) and third (2.1/annum) years. Seventy-eight per cent of pain clinic patients reduced their visits to their GP in the 12 months following treatment in the pain service, compared with 53% of patients referred to rheumatology clinics and 46% of patients with fibromyalgia. CONCLUSION: A nurse-led chronic pain clinic for fibromyalgia patients can have a positive impact on primary and secondary healthcare utilization. RELEVANCE TO CLINICAL PRACTICE: Having a designated nurse-led pain clinic can enable patients to access the appropriate service at an earlier stage in their condition and receive the support needed to manage the impact of their pain.

Iatrogenic injury of the chorda tympani: a systematic review.

OBJECTIVE: To review the currently available literature on iatrogenic injury of the adult chorda tympani. DESIGN: Systematic literature review. METHOD: Five electronic databases and one search engine were used to access available English language literature on the chorda tympani, focusing on iatrogenic injury. RESULTS: The chorda tympani is most often injured during middle-ear surgery, after which at least 15-22 per cent of patients experience symptoms, mostly changes in taste and dryness of the mouth. Numerous factors influence whether injury to the chorda tympani causes symptoms, including the extent of injury, type of surgery, age of the patient, anatomical variables and subjective adaptation. Although most patients experience gradual symptomatic recovery, complaints can be persistent and troublesome. CONCLUSION: Care should be taken to preserve the chorda tympani during middle-ear surgery, and to warn patients pre-operatively about this potential complication. This is particularly important if surgery is bilateral.

Influence of variations across the MMP-1 and -3 genes on the serum levels of MMP-1 and -3 and disease activity in rheumatoid arthritis.

Matrix metalloproteinases (MMPs) are involved in joint destruction in rheumatoid arthritis (RA), and are strongly associated with levels of inflammation. To understand the relationship between MMP-1 and -3 variants and MMP levels in RA, we investigated the genotypic and haplotypic relationships of the MMP-1 and -3 genes with circulating levels of these MMPs. The genotypes of single-nucleotide polymorphisms (SNPs) rs1799750 (1G/2G, MMP-1 promoter), rs495366 (G/A, intergene), rs679620 (A/G, MMP-3 coding region) and rs3025058 (5A/6A, MMP-3 promoter) were determined in 430 RA patients. Each polymorphism was associated with serum levels of MMP-1 (P trend <0.0001 for each SNP), with haplotype 1G-G-A-5A associated with the highest level. The intergenic and MMP-3 SNPs were associated with MMP-1 levels independent of the MMP-1 promoter SNP. The MMP-3 SNPs were associated with serum MMP-3 level (P trend <0.0001 for each SNP), and were each associated with mean time-averaged disease activity (DAS28) in patients followed up for 2 years (P=0.003). Our findings indicate that several closely linked polymorphisms in the MMP-1-MMP-3 loci have an important role in determining the circulating levels of these MMPs in RA, and that MMP-3 polymorphism is associated with the level of disease activity over time.

Clinical anatomy of the chorda tympani: a systematic review.

OBJECTIVE: The chorda tympani is at risk of iatrogenic injury throughout its course. This paper reviews the clinical anatomy of the nerve in adults. DESIGN: Systematic literature review. METHOD: Relevant English-language articles were identified using five electronic databases and one search engine. Data from approximately 70 scientific papers were supplemented with information from selected reference texts. RESULTS: The anatomy of the chorda tympani differs from standard descriptions, particularly regarding its exit from the middle ear and area of lingual innervation. Whilst it is known to convey taste sensation from the anterior two-thirds of the tongue and parasympathetic innervation to the submandibular and sublingual salivary glands, the chorda tympani probably has additional sensory and secretomotor functions. CONCLUSION: A detailed understanding of the anatomy of the chorda tympani may help to reduce the risk of iatrogenic injury during head, neck and middle-ear surgery, and to explain the variable consequences of such injury.

Antinuclear antibodies are associated with tumor necrosis factor receptor I gene polymorphism in patients with rheumatoid arthritis.

OBJECTIVES: Antinuclear antibodies (ANA) are a common feature of autoimmune diseases such as rheumatoid arthritis (RA). Herein, we investigate the relationship between ANA and polymorphism in the tumour necrosis factor receptor (TNFR) genes. METHODS: Serum titers of ANA at diagnosis were measured in 267 patients with RA and a single nucleotide polymorphism (SNP) in each of the TNFR-I (36A/G) and TNFR-II (676T/G) genes was genotyped by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) analysis. Circulating levels of soluble TNFR (sTNFR) and TNF-α were also measured in some patients. RESULTS: Our initial analyses revealed the presence of ANA was associated with the TNFR-I 36A/G SNP, with a trend of increasing ANA frequency with G allele dosage (p=0.004). ANA status was also associated with lower sTNFR-I levels and a raised sTNFR-II/sTNFR-I ratio. The TNFR-II 676T/G SNP and circulating levels of sTNFR-II and TNF-α were not associated with ANA status. In an adjusted multivariate regression model the TNFR-I 36 GG genotype (OR 7.8, p=0.008) and levels of sTNFR-I (p=0.018) were independently associated with ANA status. CONCLUSIONS: Our findings suggest a possible link between the production of ANA and the TNF-α/TNFR-I signalling system, which may be related to the apoptosis-inducing ability of this cytokine.

Long-term middle-ear ventilation with subannular tubes.

OBJECTIVE: Long-term tympanostomy tubes are associated with a significant rate of complications, particularly persistent perforation. We describe the outcomes of 57 subannular ventilation tube insertions in 45 consecutive patients. DESIGN: Retrospective case series. SUBJECTS: We studied 45 consecutive patients with chronic otitis media with effusion and hearing loss (n = 54 cases), associated with adhesive otitis media (n = 7), tympanic membrane retraction (n = 17) and tympanic membrane perforation (n = 3). The mean follow up was 48 months (range, nine to 95 months). RESULTS: The mean duration of ventilation for tubes still in situ was 22 months (range, one to 76 months; n = 29), and for tubes which extruded or were removed 23 months (range, one to 85 months; n = 28). The mean improvement in air-bone gap was 14 dB (range, -14 to 35 dB). Complications included blockage (16 per cent), perforation after extrusion (9 per cent), granulation (5 per cent) and infection (4 per cent). CONCLUSION: Subannular ventilation tubes provide an effective option for management of intractable middle-ear effusion and eustachian tube dysfunction.

Preliminary investigations of the colonisation of upper respiratory tract tissues of infants using a paediatric formulation of the oral probiotic Streptococcus salivarius K12.

A powder preparation of the oral probiotic Streptococcus salivarius K12 has been given to 19 young otitis media-prone children following a 3-day course of amoxicillin administered as a preliminary to ventilation tube placement. In two subjects, the use of strain K12 appeared to effect the expansion of an indigenous population of inhibitory S. salivarius. In other children, strain K12 colonisation extended beyond the oral cavity to also include the nasopharynx or adenoid tissue. The relatively low proportion (33%) of subjects that colonised was attributed to failure of the amoxicillin pre-treatment to sufficiently reduce the indigenous S. salivarius populations prior to dosing with strain K12 powder.

Biofilms and their role in otorhinolaryngological disease.

OBJECTIVE: To describe the pathophysiology of biofilm communities and their role in otorhinolaryngological disease, with reference to the published literature. DESIGN: Review of relevant literature, using Medline and the combined search terms 'biofilms' and 'otorhinolaryngology', and also various related keywords such as 'tonsil' and 'adenoid'. RESULTS: Description of biofilm pathophysiology and of published reports of biofilms in otorhinolaryngological disease. CONCLUSION: Virtually all microbes live in biofilm communities. Within these communities, the microbes assume differing specialised roles which confer survival advantages on the community. These communities cause chronic and device-associated infections. Within the specialist field of otorhinolaryngology, biofilms have been shown to play a role in many infections, including: chronic otitis media, cholesteatoma, chronic tonsillitis, chronic sinusitis, and infections of tracheostomies, endotracheal tubes and cochlear implants.

The overall status in rheumatoid arthritis (OSRA) measure--further evidence to support its use in clinical practice.

OBJECTIVES: The overall status in rheumatoid arthritis (OSRA) instrument is a simple summary of health status, including disease activity (OSRA-A) and damage (OSRA-D) scores. Despite evidence of the validity of the OSRA, uptake has been low. This study aimed to assess the responsiveness and re-examine the validity of the OSRA using the measures from the British Rheumatoid Outcome Study Group (BROSG) randomized controlled trial of aggressive vs symptomatic treatment of rheumatoid arthritis (RA) patients. METHODS: 466 patients were recruited. Outcome measures included the OSRA, the OMERACT core set and the DAS28, and were collected at baseline and annually for the 3 yrs of the trial. X-rays of the hands and feet were taken at baseline and 3 yrs. Patients were assigned a Townsend score (a measure of social deprivation) according to area of residence. Construct validity was assessed by correlating the OSRA with a range of outcome measures, and testing for the known inequality in RA outcome between patients classified by social deprivation. Responsiveness to change was assessed against self-reported change over the first year of the trial. RESULTS: The OSRA-A and OSRA-D measures demonstrated construct validity, performing as hypothesized. The OSRA-A was the most responsive measure in the BROSG trial in detecting patient reported improvement and deterioration. The OSRA-D demonstrated similar responsiveness to alternative measures. CONCLUSIONS: Our results demonstrate the validity and responsiveness of the OSRA, and its potential for inclusion in clinical trials. More important, as the OSRA is quick and easily calculated, uses routinely collected information, and provides useful quantitative information about a patient's status and progress it is suitable for use in the routine clinic.

How we do it: tympanoplasty: are different three- and four-frequency averages comparable?

The results of tympanoplasty may be reported in a variety of ways. Pure-tone audiometry underpins reporting, yet there is no constancy in the pure-tone threshold average used. We examine the relationship between the 0.5, 1, 2 kHz, 0.5, 1, 2, 3 kHz and 0.5, 1, 2, 4 kHz pure-tone audiometry averages. Using audiometric data collected for 77 patients, we have compared hearing threshold using three different frequency averages derived from pure-tone audiometry. The 0.5, 1, 2 kHz, 0.5, 1, 2, 3 kHz and 0.5, 1, 2, 4 kHz three- and four-frequency averages are significantly different, this difference being primarily determined by the changes in the 4-kHz threshold. Using an average including 4 kHz results in 8% few patients achieving an ABG closure to within either 10 dB or 20 dB. When comparing surgical results with others, surgeons should use reports employing comparable audiometric measures of analysis.

Malleus-stapes assembly: experience with two prostheses.

Tympanoplasty is often a necessary part of middle-ear surgery, the most common defect being that between an intact, mobile stapes and the malleus handle. The most readily available tissue is the patient's incus, reshaped to bridge the space between an intact stapes and the malleus. When the incus cannot be used, the hydroxyapatite Wehrs incus prosthesis can be used as an alternative.Twenty-six patients had an autograft incus ossiculoplasty and 20 patients underwent modified Wehrs incus prosthesis ossiculoplasty. The average post-operative air-bone gaps (ABGs) were 16.2 dB hearing loss (dBHL) and 17.2 dBHL, respectively. Air-bone gap closure to within 15 dBHL was achieved for 48 per cent of incus autografts and for 57 per cent of Wehrs prostheses, and to within 20 dBHL for 77 per cent and 62 per cent, respectively. Over four years follow up, the reconstruction was stable for each group, the ABGs being 17.7 dBHL and 17.1 dBHL, respectively.

Association between cigarette smoking and release of tumour necrosis factor alpha and its soluble receptors by peripheral blood mononuclear cells in patients with rheumatoid arthritis.

OBJECTIVE: To investigate the relationship between cigarette smoking and release of TNF-alpha and its soluble receptors (sTNFRI and sTNFRII) by peripheral blood mononuclear cells (PBMCs) from RA patients. METHODS: We studied 71 RA patients with established disease (mean duration 10.6 yr). Smoking history was established by questionnaire. T lymphocytes and monocytes were isolated from peripheral blood and incubated with or without stimulation (phytohaemagglutinin and lipopolysaccharide, respectively). Release of TNF-alpha and sTNFR into culture medium was measured by enzyme-linked immunosorbent assay. RESULTS: TNF-alpha release by stimulated T lymphocytes was significantly higher in patients with a history of smoking than in those who had never smoked (1416.0 vs 767.4 pg/ml, P = 0.04), and showed a relationship with smoking duration and intensity (P for trend < or =0.009). Monocyte TNF-alpha release was not associated with smoking status. Release of sTNFR showed no clear relationships with extent of smoking, although release by stimulated T lymphocytes was higher in past smokers than in those who had never smoked (P < or = 0.03). The ratio of TNF-alpha/sTNFR released from T lymphocytes was higher in past and current smokers, and was associated with extent of smoking. No relationship was found between smoking and plasma TNF-alpha levels, but levels of both receptors were higher in past smokers. CONCLUSION: In RA patients who smoke there is an alteration in the ratio of TNF-alpha/sTNFR released by stimulated T cells that might favour increased TNF-alpha activity. The increased TNF-alpha/sTNFR ratio is associated with extent of smoking, and remains elevated after smoking cessation.

Patients with stable long-standing rheumatoid arthritis continue to deteriorate despite intensified treatment with traditional disease modifying anti-rheumatic drugs--results of the British Rheumatoid Outcome Study Group randomized controlled clinical trial.

OBJECTIVE: Patients with rheumatoid arthritis (RA) should start treatment early with the aim of suppressing the inflammatory process completely. It is not known if this strategy should, or can, be continued in later disease. METHODS: In a multicentre, randomized, observer-blinded, controlled trial, 466 patients with established RA (>5 yr), on stable therapy for at least 6 months, were randomized to adequate symptom control/shared care setting (SCSC) or aggressive treatment/hospital setting (ATH). All were reviewed annually by a rheumatologist. The primary outcome after 3 yr was the Health Assessment Questionnaire (HAQ). Others included the OMERACT core set and the Disease Activity Score (DAS) 28. RESULTS: Three hundred and ninety-nine patients completed the trial. There was a significant deterioration in HAQ in both arms. Only the physician global score differed between the arms. CONCLUSIONS: The trial showed no additional benefit of intensified treatment with traditional disease modifying anti-rheumatic drugs (DMARDs) in patients with stable, established RA. It proved hard to suppress C-reactive protein levels. Patients in the SCSC arm were able to initiate treatment changes when their symptoms deteriorated without frequent hospital assessment. Pending further evidence, the model of shared care with annual hospital review is as good as 4-monthly hospital review for these patients.

Self-referral of symptoms (SOS) follow-up system of appointments for patients with uncertain diagnoses in rheumatology out-patients.

OBJECTIVE: Clinical features in rheumatological conditions often fluctuate with time and this may cause difficulty when evaluating patients whose symptoms or signs do not coincide with their initial rheumatology visit. The aim of this study was to evaluate the outcome of a follow-up system whereby patients with uncertain rheumatological diagnoses at their initial assessment are given easy and rapid access to a rheumatology review. METHOD: We studied the outcome of SOS (self-referral of symptoms) appointments offered to patients over a 44-month period in one consultant's clinic at the Staffordshire Rheumatology Centre. The reattendance rates and diagnoses at the initial and subsequent visits were evaluated over a mean period of 26.3 months (range 7-64 months). RESULTS: Thirty-seven patients (23 males, 14 females) were offered SOS appointments during the period studied. At the initial assessment, a provisional diagnosis was recorded for 29 patients (78.4%), whereas the diagnosis was unclear for the other eight patients. At the end of the study period, 10 patients (27%) had requested specialist review via the SOS system after a mean period of 6.8 months (1-19 months). The diagnosis remained unchanged in 8 of the 10 reattenders, whereas the diagnosis was revised in two patients. None of these patients, however, developed an inflammatory arthritis. CONCLUSION: We suggest that an SOS system of appointments may be a feasible and practical method to follow up patients who have uncertain rheumatological diagnoses at their initial visit. This follow-up system may not easily fit into the current out-patient reforms being implemented in the National Health Service, yet this form of specialist follow-up seems clinically essential for some forms of disease management. The requirements necessary to operate such a system as well as the envisaged pros and cons for the patient and for the rheumatologist are discussed.

How we do it: modified Wehrs incus ossiculoplasty.

Keypoints * Ossiculoplasty is commonly performed as part of tympanoplasty. Hydroxyapatite is a favoured material for ossicular protheses. * A modification to the Wehrs incus prosthesis is described. * Twenty-one procedures were performed on 20 patients and the results are reported. * On average there was a 4-5 dB closure of the air-bone gap (ABG), with patients having a hearing gain procedure averaging 11 dB closure. Air-bone gap closure to