Providing an extended use of an otological-specific outcome instrument to derive cost-effectiveness estimates of treatment.

OBJECTIVES: Although quality-adjusted life years (QALYs) are increasingly being used by decision-makers to make comparisons of cost-effectiveness, there are no otological-specific outcome measures that fit within this QALY framework. This study had two main objectives. The first was to provide a means to derive QALYs from a condition-specific otological instrument (Cambridge Otology Quality of Life, COQOL), and the second was to assess the convergent validity, or degree of correlation, between the COQOL and SF-6D, an established QALY instrument. DESIGN: Longitudinal cohort study designed to assess the convergent validity between SF-6D and COQOL and to generate a mapping function to enable SF-6D values to be predicted from the COQOL responses. SETTING: Cambridge University Hospital, UK. PARTICIPANTS: A total of 207 patients attending a routine outpatient general otology clinic. MAIN OUTCOME MEASURES: SF-6D and the COQOL instrument completed at baseline and again 3 months later. RESULTS: Convergent validity was demonstrated with mean SF-6D values decreasing linearly with increasing severity on the COQOL instrument. Overall, the correlation between the COQOL scores and the SF-6D values was moderate and statistically significant (r = 0.490, P = <0.001). A simple mapping model based on an ordinary least squares (OLS) regression function predicted SF-6D values from the COQOL data with a reasonable degree of accuracy. Further validation using the follow-up 3-month data confirmed the prediction power of this mapping model. CONCLUSIONS: This study provides a method for estimating QALYs from condition-specific COQOL data and provides the opportunity for the cost-effectiveness of otological treatment to be measured and placed within the national QALY framework.

The Cambridge Otology Quality of Life Questionnaire: an otology-specific patient-recorded outcome measure. A paper describing the instrument design and a report of preliminary reliability and validity.

OBJECTIVE: The Cambridge Otology Quality of Life Questionnaire (COQOL) is a patient-recorded outcome measurement (PROM) designed to quantify the quality of life of patients attending otology clinics. DESIGN: Item-reduction model. A systematically designed long-form version (74 items) was tested with patient focus groups before being presented to adult otology patients (n. 137). Preliminary item analysis tested reliability, reducing the COQOL to 24 questions. This was then presented in conjunction with the SF-36 (V1) questionnaire to a total of 203 patients. Subsequently, these were re-presented at T + 3 months, and patients recorded whether they felt their condition had improved, deteriorated or remained the same. Non-responders were contacted by post. A correlation between COQOL scores and patient perception of change was examined to analyse content validity. SETTING: Teaching hospital and university psychology department. PARTICIPANTS: Adult patients attending otology clinics with a wide range of otological conditions. MAIN OUTCOME MEASUREMENTS: Item reliability measured by item­total correlation, internal consistency and test­ retest reliability. Validity measured by correlation between COQOL scores and patient-reported symptom change. RESULTS: Reliability: the COQOL showed excellent internal consistency at both initial presentation (a = 0.90) and 3 months later (a = 0.93). Validity: One-way analysis of variance showed a significant difference between groups reporting change and those reporting no change in quality of life (F(2, 80) = 5.866, P < 0.01). CONCLUSIONS: The COQOL is the first otology-specific PROM. Initial studies demonstrate excellent reliability and encouraging preliminary criterion validity: further studies will allow a deeper validation of the instrument.

Using a tunable quantum wire to measure the large out-of-plane spin splitting of quasi two-dimensional holes in a GaAs nanostructure.

The out-of-plane g-factor g([perpendicular])(*) for quasi two-dimensional (2D) holes in a (100) GaAs heterostructure is studied using a variable width quantum wire. A direct measurement of the Zeeman splitting is performed in a magnetic field applied perpendicular to the 2D plane. We measure an out-of-plane g-factor up to g([perpendicular])(*) = 5, which is larger than previous optical studies of g([perpendicular])(*) and is approaching the long predicted but never experimentally verified out-of-plane g-factor of 7.2 for heavy holes.

Conservative management, surgery and radiosurgery for treatment of vestibular schwannomas: a model-based approach to cost-effectiveness.

OBJECTIVE: To undertake a cost-effectiveness analysis comparing conservative management, surgery and radiosurgery for treating small-to-medium (1-20 mm)-sized vestibular schwannomas. DESIGN: Model-based economic evaluation using individual-level data from a Birmingham-based longitudinal patient database and from published sources. Both a decision tree and state-transition (Markov) model were developed, from an National Health Service (NHS) perspective. Sensitivity analyses were also carried out. SETTING: Secondary care treatment for patients with small-to-medium-sized vestibular schwannomas. PARTICIPANTS: Three hypothetical cohorts of adult patients receiving conservative management, radiosurgery or surgery treatment, aged 58 years as starting age within model. MAIN OUTCOME MEASURES: Cost-effectiveness based on cost per quality-adjusted life year (QALY). RESULTS: Conservative management is the preferred strategy for the treatment of small-to-medium-sized vestibular schwannomas. Conservative management is both cheaper (-£ 722 and -£ 2764) and more effective (0.136 and 0.554 quality-adjusted life years) than both radiosurgery and surgery, respectively. A conservative strategy can therefore be considered as highly cost-effective. This result is sensitive to the assumed quality-of-life parameters in the model. Sensitivity analysis suggests that the probability of a conservative strategy being the most cost-effective approach compared with surgery and radiosurgery at a willingness to pay of £ 20 000/quality-adjusted life year gained is 80% and 55%, respectively. CONCLUSIONS: A conservative approach is the preferred strategy for treatment of small-to-medium vestibular schwannomas. This result is sensitive to quality-of-life values used in the analysis. More research is required to assess the impact of treatment upon patients' health-related quality of life over time.

Open and closed cavity mastoid operations: comparing early hearing results.

The aim of the study is to compare audiological results in patients treated surgically with either an open or closed cavity mastoidectomy. A prospective review of a single surgeon's case series based at two district general hospitals. All patients with 1-year post-operative hearing results following an open or closed cavity mastoid surgery were included. Outcome measured included the preoperative and postoperative air-bone gap (ABG). Belfast rule of thumb was used to assess the benefit from middle ear surgery. A total of 128 patients were identified from the database with 1 year post-operative hearing results. Sixty-three patients had undergone an open cavity mastoidectomy and 65 had a closed cavity mastoidectomy. The mean post-operative ABG in patients with open cavity mastoidectomy was 24 dB and for closed cavity 21 dB (p = 0.12). There was no statistical difference between open and closed cavity mastoidectomy with or without ossiculoplasty and if the underlying pathology was squamous or mucosal disease. However, patient with post-operative ABG below or equal to 20 dB was 41% for closed cavity compared to 21% for open cavity. Using the Belfast rule of thumb, 79% of the patients in both groups had successful hearing results post surgery. The 1-year post-operative audiological results between open and closed cavity masoidectomy showed no statistical difference. The pathology affecting the middle ear also had no influence on the hearing results between the two groups. However, there was a higher percentage of patients with closed cavity procedures who had a post-operative ABG that was below or equal to 20 dB.

The bone-anchored hearing aid in the rehabilitation of single-sided deafness: experience with 58 patients.

OBJECTIVES: To assess the efficacy of the bone-anchored hearing aid (BAHA) in the rehabilitation of single-sided deafness (SSD). STUDY DESIGN: Retrospective case-control series review. SETTING: Tertiary referral unit. PATIENTS: Fifty-eight consecutive patients that had a bone-anchored hearing aid for single-sided deafness completed outcome questionnaires, building upon earlier audiological assessment of 19 patients. Single-sided deafness controls (n = 49) were mainly acoustic neuroma patients. MAIN OUTCOME MEASUREMENTS: speech discrimination testing in directional noise, speech and spatial qualities of hearing questionnaire and the Glasgow Benefit Inventory (GBI). RESULTS: The mean follow-up time was 28.4 months. Five (13%) of the bone-anchored hearing aid patients were non-users because of lack of benefit. The audiometric testing confirmed that when noise was on the bone-anchored hearing aid side speech perception was reduced but benefited when noise was on the side of the hearing ear. There was no difference between the Speech and Spatial Qualities of Hearing Scores in bone-anchored hearing aid users and controls. In particular there was no difference in the spatial subscores. In the bone-anchored hearing aid users the median Glasgow Benefit Inventory score was 11. If the non-users are included then 13 (22%) patients had no or detrimental (negative) Benefit scores. No or negative benefit scores were more frequent in those deaf for <10 years. In open-field questions, patients felt the bone-anchored hearing aid was most useful in small groups or in 'one-to-one' conversation. CONCLUSIONS: Bone-anchored hearing aid rehabilitation for single-sided deafness is less successful than for other indications, reflected here by relatively low median Glasgow Benefit Inventory scores. There was also no significant difference between controls and bone-anchored hearing aid users in the Speech and Spatial Qualities of Hearing Questionnaire. Patients with a longer duration of deafness report greater subjective benefit than those more recently deafened, perhaps due to differing expectations.

Results of primary ossiculoplasty in ears with an intact stapes superstructure and malleus handle: inflammation in the middle ear at the time of surgery does not affect hearing outcomes.

OBJECTIVE: To determine whether any factors are predictive of success or failure in primary ossiculoplasty employing autologous bone in Austin-Kartush Group A (stapes and malleus handle present) ears. STUDY DESIGN: Retrospective review of a single-surgeon case series. SETTING: Two District General Hospitals in the United Kingdom. PATIENTS: Of 135 patients undergoing primary repair, 116 had sufficient data for analysis (mean follow-up 33 months). MAIN OUTCOMES MEASURED: Postoperative air-bone gaps (pABG) in patients with differing qualities of middle-ear mucosa (active versus inactive), differing pathologies (mucosal versus squamous) and differing surgical procedures [canal-wall up (CWU) versus canal-wall down (CWD)]. SECONDARY OUTCOME MEASURE: 'Belfast Rule of Thumb' (operated ear hearing brought to 30 dB or better or to within 15 dB of contralateral ear). RESULTS: Postoperative ABGs were closed within 10 dB in 37%, 20 dB in 74% at latest follow-up. The only significant factors predicting hearing outcomes were the status of the canal wall (CWU = 14.1 dB, CWD = 24.7 dB: significant, P = 0.00) and whether surgery was primary or revision. Mean ABG was 14.7 for inactive middle ear mucosa, 17.2 for active middle ear mucosa (not significant, P = 0.25). Excluding CWD procedures from the analysis improved outcomes to 80% (within 20 dB) and 41% (within 10 dB) overall, and the mean for active and inactive ears to 14.2 and 14.0 dB respectively. Postoperatively, 82% of patients fulfilled the 'Belfast Rule of Thumb'. CONCLUSION: The most significant prognostic factor affecting hearing outcomes - status of the canal wall - is independent of staging. The factor most associated with staging - the status of the middle ear mucosa - is only weakly associated with a successful functional outcome.

Conservative versus primary surgical treatment of acoustic neuromas: a comparison of rates of facial nerve and hearing preservation.

OBJECTIVES: To determine whether patients with small to medium sized acoustic neuromas managed conservatively suffer reduced rates of facial nerve and hearing preservation when compared with patients undergoing primary surgery. DESIGN: An intention-to-treat comparison between patients managed conservatively at first presentation and those managed with primary surgery. SETTING: Tertiary referral neurotological centre in Birmingham, UK. PARTICIPANTS: Data were drawn from our database of 487 sporadic acoustic neuromas managed from 1997 to present day. MAIN OUTCOME MEASURES: Facial nerve status (assessed using the House-Brackmann system) was collated for all conservatively managed patients (n = 167) and compared with that expected when calculated from primarily surgically managed tumours of equivalent size (n = 121). A chi-square test was employed to test the statistical significance of any difference. Hearing preservation (maintenance of AAO-HNS Class) in patients presenting with Class A or B hearing was compared between conservatively managed patients and those with primary surgical management. RESULTS: Observed facial nerve preservation in conservatively managed patients was significantly better (P < 0.001) than expected when calculated from rates of facial nerve preservation in surgically managed patients. Hearing preservation was also significantly more successful in conservatively managed patients (Pearson chi-square: P < 0.000). CONCLUSIONS: An initial period of conservative management is a safe and reasonable management policy in all acoustic neuromas up to 2 cm in size at the cerebello-pontine angle. Given that there are no failsafe ways of deciding potential for growth in acoustic neuromas, initial conservative management of these tumours offers superior hearing and facial nerve preservation when compared with primary surgical treatment.

Initiated chemical vapor deposition of antimicrobial polymer coatings.

The vapor phase deposition of polymeric antimicrobial coatings is reported. Initiated chemical vapor deposition (iCVD), a solventless low-temperature process, is used to form thin films of polymers on fragile substrates. For this work, finished nylon fabric is coated by iCVD with no affect on the color or feel of the fabric. Infrared characterization confirms the polymer structure. Coatings of poly(dimethylaminomethyl styrene) of up to 540 microg/cm2 were deposited on the fabric. The antimicrobial properties were tested using standard method ASTM E2149-01. A coating of 40 microg/cm2 of fabric was found to be very effective against gram-negative Escherichia coli, with over a 99.99%, or 4 log, kill in just 2 min continuing to over a 99.9999%, or 6 log, reduction in viable bacteria in 60 min. A coating of 120 microg/cm2 was most effective against the gram-positive Bacillus subtilis. Further tests confirmed that the iCVD polymer did not leach off the fabric.

Seeing shapes in seemingly random spatial patterns: Fractal analysis of Rorschach inkblots.

Rorschach inkblots have had a striking impact on the worlds of art and science because of the remarkable variety of associations with recognizable and namable objects they induce. Originally adopted as a projective psychological tool to probe mental health, psychologists and artists have more recently interpreted the variety of induced images simply as a signature of the observers' creativity. Here we analyze the relationship between the spatial scaling parameters of the inkblot patterns and the number of induced associations, and suggest that the perceived images are induced by the fractal characteristics of the blot edges. We discuss how this relationship explains the frequent observation of images in natural scenery.

An investigation into the role of Chlamydophila spp. in bovine upper respiratory tract disease.

An outbreak of upper respiratory tract disease was investigated in a group of 17 housed home-bred calves on a mixed dairy, beef and sheep farm in Devon. Conjunctival swabs were collected and tested for Chlamydophila spp. DNA using a PCR test that detects Chlamydophila abortus and Chlamydophila psittaci. Six of the calves tested gave a positive result. Further epidemiological observations and laboratory testing indicated that the adult dairy cows, from which the affected calves originated, were the most likely source of infection.

A large and uncharacteristically aggressive cholesterol granuloma of the middle ear.

Cholesterol granulomas of the middle ear tend to be benign in nature, frequently seen by otologists during cholesteatoma or chronic otitis media surgery and easily dealt with by evacuation. In contrast, cholesterol granulomas of the petrous apex appear to have a more aggressive nature and present significant pathological threats. We present a case of a large destructive cholesterol granuloma of the middle ear eroding the middle and posterior cranial fossa bone and dura to exert a mass effect upon the temporal lobe. We emphasize the destructive potential of this extremely rare middle-ear cholesterol granuloma, and draw attention to the distinction between this variant and the commonplace and benign form of the lesion more usually found at this site. We also present the current theories of the aetiology of cholesterol granuloma formation with possible explanations for the rare aggressive behaviour.

Perceptual and physiological responses to the visual complexity of fractal patterns.

Fractals have experienced considerable success in quantifying the complex structure exhibited by many natural patterns and have captured the imagination of scientists and artists alike. With ever widening appeal, they have been referred to both as "fingerprints of nature" and "the new aesthetics." Our research has shown that the drip patterns of the American abstract painter Jackson Pollock are fractal. In this paper, we consider the implications of this discovery. We first present an overview of our research from the past five years to establish a context for our current investigations of human response to fractals. We discuss results showing that fractal images generated by mathematical, natural and human processes possess a shared aesthetic quality based on visual complexity. In particular, participants in visual perception tests display a preference for fractals with mid-range fractal dimensions. We also present recent preliminary work based on skin conductance measurements that indicate that these mid-range fractals also affect the observer's physiological condition and discuss future directions based on these results.

Quantitative histochemical determination of muscle enzymes: biochemical verification.

We established quantitative histochemical assays for the enzymatic activity of succinate dehydrogenase and alpha-glycerol phosphate dehydrogenase for cat skeletal muscle. A computer-enhanced image analysis system was used to quantitate the histochemical enzyme-activity reaction products. We describe a series of experiments that verify the reliability and validity of the assays. Histochemically determined enzyme activities were linear with respect to tissue thickness and reaction time. Biochemically determined enzyme activities were also linear with respect to tissue thickness and incubation time. Consecutive tissue sections, assayed either histochemically or biochemically, were used to establish a linear regression equation that allowed quantitative histochemically determined reaction rates, measured in optical density per minute, to be calibrated as nanomoles per minute.

Distribution of muscle fiber types and EMG activity in cat intercostal muscles.

The electromyogram (EMG) activity and histochemical properties of intercostal muscles in the anesthetized cat were studied. The parasternal muscles were consistently active during inspiration. The external intercostals in the rostral spaces and the ventral portions of the midthoracic spaces were also recruited during inspiration. The remaining external intercostals were typically silent, regardless of the level of respiratory drive. The internal intercostal muscles located in the caudal spaces were occasionally recruited during expiration. There was a clear correlation between recruitment patterns of the intercostals and the histochemically defined fiber type properties of the muscles. Intercostal muscles that were routinely recruited during inspiration had a significantly higher proportion of slow-oxidative muscle fibers.

Influence of spaceflight on rat skeletal muscle.

The size, succinate dehydrogenase (SDH) and alpha-glycerolphosphate dehydrogenase (GPD) activities, and alkaline myofibrillar adenosinetriphosphatase (ATPase) staining properties were determined from quantitative histochemical analyses of single fibers from five hindlimb muscles of six male rats exposed to a 7-day National Aeronautics and Space Administration spaceflight mission (SL-3). These same properties were determined in a group of ground-based control rats housed under simulated environmental conditions. The wet weight of each of the flight muscles was significantly reduced relative to control. However, the loss of mass varied from 36% in the soleus to 15% in the extensor digitorum longus. The cross-sectional areas of fibers in the flight muscles also were reduced, except for the dark ATPase fibers in the medial gastrocnemius. The greatest relative fiber atrophy occurred in the muscles with the highest proportion of light ATPase fibers. An increase in the percentage of dark ATPase fibers also was observed in flight muscles with a predominance of light ATPase fibers. Also, there was an increase in the biochemically determined myofibrillar ATPase activity of tissue sections of the flight soleus. No changes in histochemical or biochemical measures of ATPase activity were observed in the flight extensor digitorum longus. In general, the SDH activity of flight muscles was maintained, whereas GPD activity either was maintained or increased. Based on a metabolic profile of ATPase, SDH, and GPD, there was an increase in the proportion of fast oxidative-glycolytic fibers in some muscles.

Influence of electrical stimulation on the morphological and metabolic properties of paralyzed muscle.

Selected morphological and metabolic properties of single fibers were studied in biopsy samples from the tibialis anterior of normal control and spinal cord-injured (SCI) subjects. In the SCI subjects, one muscle was electrically stimulated progressively over 24 wk, in 6-wk blocks for less than or equal to 8 h/day, while the contralateral muscle remained untreated. The percentage of fibers classified as type I [qualitative alkaline preincubation myofibrillar adenosinetriphosphatase (ATPase)] was significantly less in the unstimulated paralyzed muscles than in the muscles of normal control subjects. Electrical stimulation increased the proportion of type I fibers in the SCI subjects. For both type I and type II fibers, the cross-sectional area, activities of myofibrillar ATPase and succinate dehydrogenase, and the capillary-to-fiber ratio were also significantly less in the paralyzed muscles than in the normal control muscles. Electrical stimulation increased only the activity of succinate dehydrogenase in both fiber types of the SCI subjects. These data are discussed in relation to the electromechanical properties of the respective muscles described in an accompanying paper (J. Appl. Physiol. 72: 1393-1400, 1992). In general, the electrical stimulation protocol used in this study enhanced the oxidative capacity and endurance properties of the paralyzed muscles but had no effect on fiber size and strength.

Incomplete normalization of dog gracilis muscle grafts with neurovascular repair despite long-term recovery.

Skeletal muscle grafts performed with neurovascular repair are used extensively in clinical situations. However, most controlled experimental studies on the efficacy of such grafts have been conducted on muscles with a relatively small mass and over a limited recovery period. Therefore, selected cellular and matrix component properties of the comparatively large dog gracilis muscle (75 g) were studied 9-12 mo after orthotopic neurovascular grafting. The grafted muscle wet weights were 71% of the contralateral control (sham-operated) muscles. In addition, the concentrations of noncollagenous protein (13%), DNA (28%), and RNA (34%) were significantly reduced in the grafts. However, the concentration of collagen was significantly higher (41%) in the grafts. In this regard, the type III collagen phenotype showed the greatest relative increase. There was no difference between the grafted and control proteoglycan concentration. The metabolic profiles of the grafted muscles were significantly different from control. The activities of myofibrillar adenosinetriphosphatase (34%) and alpha-glycerophosphate dehydrogenase (25%) were reduced, whereas citrate synthase remained unchanged. These data suggest that recovery of up to 1 yr was insufficient for the normalization of several connective tissue matrix components and biochemical properties of the grafts.

Altered distribution of mitochondria in rat soleus muscle fibers after spaceflight.

The influence of spaceflight on the distribution of succinate dehydrogenase (SDH) activity throughout the cross section of fibers in the soleus was studied in five male rats and in five rats maintained under ground-based simulated flight conditions (control). The flight (COSMOS 1887) was 12.5 days in duration, and the animals were killed approximately 2 days after return to 1 G. Fibers were classified as slow-twitch oxidative or fast-twitch oxidative-glycolytic in histochemically prepared tissue sections. The distribution of SDH activity throughout the cross section of 20-30 fibers (each type) was determined using quantitative histochemical and computer-assisted image analysis techniques. In all the fibers, the distribution of SDH activity was significantly higher in the subsarcolemmal than in intermyofibrillar region. After spaceflight the entire regional distribution of SDH activity was significantly altered in the slow-twitch oxidative fibers. The fast-twitch oxidative-glycolytic fibers of the spaceflight muscles exhibited a significantly lower SDH activity only in their subsarcolemmal region. These data suggest that when determining the influence of spaceflight on muscle fiber oxidative metabolism enzymes, it is important to consider the location of the enzyme throughout the cross section of a fiber. Furthermore the functional properties of the soleus that depend on the metabolic support of mitochondria in the subsarcolemmal region may be primarily affected by exposure to microgravity.