Diagnostic and prognostic prediction models.

Risk prediction models can be used to estimate the probability of either having (diagnostic model) or developing a particular disease or outcome (prognostic model). In clinical practice, these models are used to inform patients and guide therapeutic management. Examples from the field of venous thrombo-embolism (VTE) include the Wells rule for patients suspected of deep venous thrombosis and pulmonary embolism, and more recently prediction rules to estimate the risk of recurrence after a first episode of unprovoked VTE. In this paper, the three phases that are recommended before a prediction model may be used in daily practice are described: development, validation, and impact assessment. In the development phase, the focus is on model development commonly using a multivariable logistic (diagnostic) or survival (prognostic) regression analysis. The performance of the developed model is expressed by discrimination, calibration and (re-) classification. In the validation phase, the developed model is tested in a new set of patients using these same performance measures. This is important, as model performance is commonly poorer in a new set of patients, e.g. due to case-mix or domain differences. Finally, in the impact phase the ability of a prediction model to actually guide patient management is evaluated. Whereas in the development and validation phase single cohort designs are preferred, this last phase asks for comparative designs, ideally randomized designs; therapeutic management and outcomes after using the prediction model is compared to a control group not using the model (e.g. usual care).

Multiple imputation to correct for partial verification bias revisited.

Partial verification refers to the situation where a subset of patients is not verified by the reference (gold) standard and is excluded from the analysis. If partial verification is present, the observed (naive) measures of accuracy such as sensitivity and specificity are most likely to be biased. Recently, Harel and Zhou showed that partial verification can be considered as a missing data problem and that multiple imputation (MI) methods can be used to correct for this bias. They claim that even in simple situations where the verification is random within strata of the index test results, the so-called Begg and Greenes (B&G) correction method underestimates sensitivity and overestimates specificity as compared with the MI method. However, we were able to demonstrate that the B&G method produces similar results as MI, and that the claimed difference has been caused by a computational error. Additional research is needed to better understand which correction methods should be preferred in more complex scenarios of missing reference test outcome in diagnostic research.

Contribution of vibration to musculoskeletal disorders in New Zealand.

The aim of this study was to remind Australasian doctors about the importance of vibration as an occupational exposure capable of causing musculoskeletal disease. This is a common problem in the northern hemisphere, but only four reports have been found in Australasian published work. Nine cases are reported together with a summary of vibration disorders and their nomenclature. Of the nine cases reviewed, six arose from compensation disputes and two resulted in Department of Labour prosecutions. Three patients had hand symptoms arising from using vibrating concrete drills, two patients used heavy floor-polishing machines in hospitals and three used heavy metal polishing machines. One had general pain from whole-body vibration in a digging machine. Minor circulatory signs were found in two patients, but cold exposure was not noted. Vibration disease is underreported in New Zealand. Doctors must question patients about vibration exposure in taking an occupational history, as vibration is an important factor in the causation of occupational musculoskeletal disorders. As vibration can be controlled, illness can be prevented.

Fluoride therapy for cochlear otosclerosis? an audiometric and computerized tomography evaluation.

The progress of sensorineural hearing loss (SNHL) in patients with cochlear otosclerosis was compared for 19 patients treated with fluoride for 1-5 years and 22 untreated controls. CT scans of eight patients before and after fluoride treatment were evaluated visually. Fluoride therapy arrested the progression of SNHL in the low (250, 500 and 1,000 Hz) (p < 0.001) and high (2 and 4 kHz) (p = 0.008) frequencies. It seemed to be more effective for the higher frequencies in cases with an initial SNHL of < 50 dB. Fluoride administration for 4 years did not seem to be superior to a shorter treatment period (1-2 years). For six patients followed up after discontinuing fluoride therapy there was minimal deterioration in SNHL. There was no clear relationship between the size and site of otospongiotic lesions on CT and the severity of SNHL. Follow-up with CT evaluation did not provide reliable information as to the efficacy of fluoride therapy.

Dehiscence of the jugular bulb in Crouzon's disease.

Patients with Crouzon's disease have a distorted nasopharynx, which frequently leads to retained middle ear secretions and necessitates myringotomy. A review of the computed tomographic (CT) scans of 21 ears in 11 patients with Crouzon's disease found that 12 jugular bulbs were protruding or dehiscent. The relationship between the jugular bulb and the middle ear space was normal bilaterally in only 2 of the 11 patients. Consequently, patients with Crouzon's disease are at risk for inadvertent puncture of the jugular bulb during myringotomy. CT scans obtained prior to myringotomy can be helpful in detecting dehiscent or protruding jugular bulbs.

Densitometry of the cochlear capsule and correlation between bone density loss and bone conduction hearing loss in otosclerosis.

Radiodensity of the bony cochlear capsule was investigated by CT-scanning in 134 ears with otosclerosis and 35 normal control ears. A technique of densitometry of the cochlea was developed comprising the measurement of maximum and minimum density together with mapping of the cochlea and measurement of the density at six predefined points in the cochlear capsule. Bone density in the normal cochlea showed very little interindividual variation. In the otosclerosis patients, minimum density was decreased in 58% of the ears, indicating the presence of a focus. At visual examination, foci were only detectable when density loss exceeded 200 Hounsfield. A positive correlation was found between bone density loss and bone conduction hearing loss with a maximum at 2,000 Hz and the medioventral point of the cochlear wall. The method appears to be useful for the follow-up during fluoride treatment, as is demonstrated by a case report.

Labyrinthine otosclerosis studied with a new computed tomography technique.

Forty-two patients (84 ears) with surgically confirmed otosclerosis were examined with a computerized tomographic scanner (Philips Tomoscan 310) equipped with a table swivel mechanism. All ears were scanned in the horizontal and a new semilongitudinal plane. In patients with an unimpaired bone conduction threshold, a normal labyrinthine capsule was found in all ears except two. Normal bone conduction does not exclude extensive labyrinthine otospongiosis. In cases with bone conduction impairment, the bony labyrinth appeared normal in about half the ears. In the other half, areas of bone resorption were present and a positive correlation was found between the degree of bone loss and the amount of bone conduction threshold loss.

[Feasibility of high resolution CT in the demonstration of the vestibular aqueduct (Ménière) and otospongiosis of the labyrinth]. / Die Anwendbarkeit der hochauflösenden CT zur Darstellung des Aquaeductus vestibuli (Ménière) und der Otospongiosis des Labyrinths.

Ever since the introduction of temporal bone imaging by means of high-resolution CT, it appears that the combination of high spatial resolution, high density resolution and the freedom of patient positioning for scanning of optimal otological planes may play a unique role in the diagnosis and follow-up of a number of otological disorders. Two examples are described here. The first is the possibility of determining whether the vestibular aqueduct in idiopathic Ménière's disease is obliterated or not, and if so, whether it is a bony or a fibrous obliteration. Although the results are preliminary, there are indications that all three cathegories occur and that the efficacy of drainage of the endolymphatic sac can be evaluated prior to surgery. The second example is the possibility of outlining and quantifying the bone mineral loss in cases of labyrinthine otospongiosis. Preliminary studies have outlined that there is a relationship between the degree of decalcification and the severity of sensorineural hearing loss. These examples show high-resolution, thin-section multiplanar CT to have great potential in the diagnosis and treatment of otological disorders. This will become evident as the techniques that were used here are worked out in more detail and become more widely known.

CT of cochlear otosclerosis (otospongiosis).

High-resolution CT is the method of choice in determining the extent of demineralization in otospongiosis. By comparing the maximum and minimum densities, this examination has become of clinical importance in the diagnostic approach to otosclerosis and in the follow-up of fluorine therapy.