Everyday Clinical Use Research Articles

Threshold 3: the feasibility of the Threshold Assessment Grid (TAG) for routine assessment of the severity of mental health problems.

Evidence-based practice requires the development of measures which are suitable for everyday clinical use ('feasible'). There is no consensus as to how to establish feasibility. The feasibility of a new assessment - the Threshold Assessment Grid (TAG) - for use when making referrals to mental health services was tested by training mental health teams in using the TAG and other standardised assessments, asking referrers to ten mental health services in London also to complete a TAG, surveying TAG users, and evaluating a feedback meeting at which TAG data were presented. One hundred and one (61%) mental health staff received training, and 445 (74%) referrers of 600 patients completed TAGs. Sixty-five (65%) questionnaires from TAG users were completed, and 24 (80%) people attending feedback meetings evaluated the TAG. These allowed the extent to which the TAG is brief, simple, relevant, acceptable, available and valuable to be investigated. The TAG exhibited good feasibility when used by mental health staff, and moderate feasibility when used by referrers. This approach can be used to investigate the feasibility of other standardised assessments.

Rasch analysis of the hierarchical assessment of balance and mobility (HABAM)

Measuring changes in mobility and balance offers a means of responding to the clinically important challenge of tracking progression and recovery in frail elderly patients who become ill. This article uses Rasch analysis to construct an interval scale from ordinal observations of such changes, using the Hierarchical Assessment of Balance and Mobility (HABAM) on 204 frail elderly inpatients. Principal components analysis confirmed the unidimensionality of the scale. The Rasch analysis confirmed the hierarchy of the HABAM, and pointed to gaps and redundant items. On this basis, an improved version of the HABAM was developed, suitable in its graphical form for everyday clinical use and for research, using the interval numbers that were generated.

Preliminary report: Dynamic stereopsis in patients with impaired binocular function

In this study, 46 strabismic patients aged between 9 and 58 years were tested for dynamic stereopsis in the peripheral visual field with up to 20° eccentricity. Squint angles ranged from +30 to -36 degrees. The effect of surgical realignment of the visual axes on dynamic stereopsis was tested before and after surgery in 40 of these patients. Of the 46 patients, 23 had esotropia and 23 exotropia. A test device was used which presented two projected squares in polarized light (each square being perceived monocularly through a polarization filter) in horizontal motion, thus creating a three-dimensional impression. Patients were tested qualitatively for dynamically stereoactive fields of vision and quantitatively for the threshold value needed to create a three-dimensional impression. We found residual dynamic stereopsis in 30% of patients who had no central static stereopsis. 56% of the patients improved after surgery, either through a significant (p < 0.01) gain of stereoactive fields or through a decrease in threshold values. This emphasizes the necessity of creating a test device suitable for everyday clinical use. Strabismus surgery is especially beneficial in connection with traffic and sports medicine, regardless of the effect on classical tests.

Prescription-event monitoring--recent progress and future horizons.

Post-marketing surveillance (PMS) is essential because the safety database on newly licensed drugs is limited by both the number and characteristics of the patients involved. In the UK, for example, successful applications for product licences for medicines containing new active substances include, as a safety database, information on a median number of 1480 (range 129–9400) patients [1]. Most of these patients will have been carefully chosen to have only one disease being treated with one drug. Few, if any of them, will be typical of the patients likely to receive the drug once it has been marketed. The identification of uncommon, even if serious or lethal, adverse reactions from such a small number of highly selected patients is unlikely. This led the Committee on Safety of Drugs (the forerunner of today's Committee on Safety of Medicines) to conclude that ‘It is well recognised that no drug which is pharmacologically effective is without hazard. Furthermore not all hazards can be known before a drug is marketed: neither tests in animals nor clinical trials in patients will always reveal all the possible side effects of a drug. These may only be known when the drug has been administered to large numbers of patients over considerable periods of time’. The Committee on Safety of Drugs Annual Report [2] which contained these remarkable conclusions was for 1969/1970. Thus, for almost 30 years it has been recognised that drug safety in clinical practice cannot depend solely upon pre-marketing data. The backbone of the post-marketing techniques that have been developed to survey the use of newly marketed drugs in large populations is provided by the hypothesis-generating methods, including spontaneous adverse drug reaction (ADR) reporting and prescription-event monitoring (PEM). The findings of such studies can be confirmed or refuted by hypothesis-testing techniques, such as case-control or cohort studies or randomised controlled clinical trials. Computerised clinical data are currently available from completed PEM studies of 58 newly marketed medicines and, as shown in Table 1, these studies have an average cohort size of 10 624 (median 11 081; range 1371–17 329) patients. Thus, PEM frequently enlarges the available safety database on newly marketed medicines. It also provides information on the ‘real-world’ use of these medicines: the data show the age, sex and geographical distribution that typifies the everyday clinical use of these drugs in general medical practice. Table 1 Details of 58 complete PEM studies. This paper briefly reviews the methodology of PEM and the current and planned activities that relate to this technique.

Perioperative analgesia with non-steroidal analgesics

Non-steroidal anti-inflammatory drugs are widely used for perioperative analgesia as a sole analgesic after minor surgical procedures and in combination with other types of analgesics after major surgery. The development and use of new selective cyclo-oxygenase-2 inhibitors hopefully reduce the likelihood of perioperative adverse effects that may prevent the use of non-steroidal anti-inflammatory analgesics in many patients. It remains to be determined, however, whether they can offer effective analgesia with minimal risks of side-effects in everyday clinical use.

Multicentre clinical evaluation of vigabatrin (Sabril ®) in mild to moderate partial epilepsies

Vigabatrin (VGB) has been shown through several studies to be safe and effective as add-on therapy, particularly for the treatment of partial seizures in patients with severe epilepsies followed for years in hospital-based clinics. We now report additional clinical experience with VGB arising from an open trial of add-on VGB therapy in patients with relatively few seizures followed by qualified neurologists in private practice (the French Neurologists Sabril Study Group). VGB was administered to 397 patients aged 12-74 years (mean age = 37.5 +/- 13.8 years) who presented with no more than seven partial seizures of any type per month during a 3-month baseline period (mean number of seizures = 3.7 +/- 1.9/month). Simple partial seizures were reported in 121 (30.5%) patients, complex partial seizures in 282 (71.0%) and seizures with secondary generalization were reported in 111 (28.0%). The mean number of associated antiepileptic drugs (AEDs) was 1.9 +/- 0.9 and the mean dose of VGB was 2.21 +/- 0.64 g/day. Following introduction of VGB, 53 (13.4%) became seizure-free and remained so during the whole trial. During the fourth month of treatment, 158 patients (39.8%) had no seizures at all and a further 69 (17.4%) had their seizure frequency reduced by more than 50%. Secondary generalization was controlled during the whole period of treatment in 55 out of 97 patients (56.7%), 17 of which remained free of all types of partial seizures. VGB showed a good tolerability profile; adverse experiences more frequently reported were drowsiness and sleep disturbances. No action was necessary in the great majority of cases; the dose was reduced in 26 (6.5%) and VGB was discontinued in 32 (8%) patients. These data provide additional evidence that VGB can be used safely early on to treat patients with mild to moderate partial epilepsies. Secondary generalization was controlled in the majority of patients. Factors associated with the everyday clinical use of VGB, that resulted from a series of organized meetings with the investigators, are discussed.

Evaluation of a Clinical Score for Prognostic Stratification of Elderly Stroke Patients

Orpington Prognostic Score (OPS) is a clinically derived score which incorporates measures of motor deficit, proprioception, balance and cognition. OPS and urinary continence were measured prospectively in 217 stroke survivors over 75 years of age at 1, 2 and 4 weeks after stroke and were correlated with dependence at discharge. Three levels of dependence were defined based on personal self-care abilities. OPS ranged from 2.0 to 3.2 (median 2.8) at 2 weeks after stroke in patients independent at discharge (n = 54). Their initial median Barthel index of 4 improved by a median of 12. Urinary continence was achieved in 95% of these patients by 2 weeks. All patients were discharged home, 39 (72%) within 4 weeks. Patients with limited dependence at discharge (n = 129) had OPS of 3.2-4.8 (median 4.0) at 2 weeks. Two-thirds were continent at 2 weeks. Their initial median Barthel index was 2 and changed by a median of 12. Seventy-one (55%) of these patients went home. OPS ranged from 5.2 to 6.8 (median 6.0) at 2 weeks in patients dependent at discharge (n = 34). About 20% of these patients were continent. Their initial median Barthel index of 2 improved by a median of 6 at discharge. Only five (15%) patients in this group went home. OPS was comparable with urinary incontinence for sensitivity (96% vs. 90%), specificity (36% vs. 39%) and accuracy (75% vs. 66%) in identifying stroke patients achieving independent living. OPS had a greater predictive value than urinary incontinence in identifying patients requiring institutional care (82% vs. 57%). OPS is a simple objective predictor of outcome in elderly stroke patients, suitable for everyday clinical use. It also can facilitate stroke research by identifying a 'middle group' of patients who would be most sensitive to changes in therapy or organization of stroke services.

The Efficacy of Lithium in Prophylaxis of Unipolar Depression Evidence from its Discontinuation

Forty unipolar patients satisfying DSM-III criteria for major depression who discontinued lithium therapy were retrospectively compared with 105 similar patients who continued the drug and served as a control group. The time to readmission from starting lithium was compared while both groups were still on lithium, and after discontinuation in one group and further continuation in the control group. The progressive increase in the probability of recurrence over two years was the greatest after discontinuation of lithium. For the patients who eventually discontinued lithium, the cumulative probability of recurrence in two years was 0.08 on lithium and 0.58 after stopping it. The probability of recurrence was unchanged over the duration of the study for patients who continued to take lithium. There was no evidence of a lithium withdrawal syndrome within three months of stopping the drug. The results support the view that the everyday clinical use of lithium as prophylaxis is beneficial in unipolar depression.

Development of a microcomputer based system for the quantification of coronary arterial disease

The Quantitative Angiographic Mensuration System consists of a standard 35 mm X-ray ciné projector, microcomputer, rear projection graphics table and printer. Projected frames from the catheter investigation are digitized directly from the tablet surface and transmitted in real time to the microcomputer. Subsequently, custom written software corrects for image distortion and data inconsistency before producing relative and absolute measurements which characterize coronary arterial disease morphology. This software has proved repeatable and objective over a series of trials with standard errors of measurement for average maximal artery diameter being 0·015 mm and 0·140 mm respectively. On validation, dimensional results are not significantly different from test objects. This system is proving worthy as a research tool and now requires further development in order to establish a place in everyday clinical use.

Immobilised enzymes as drugs

The main objective of the work is to present the state of the art in a relatively new field of biotechnology — the use of immobilised enzymes in applied medicine. Enzyme therapy seems to be promising in the treatment of cardiovascular, oncological, intestinal, viral and hereditary diseases. At the same time there exist many limitations for the everyday clinical use of native enzymes. Enzymes are unstable, have a short lifetime in the circulation, cause toxic and immune reactions, and are costly, etc. These drawbacks can be at least partially eliminated by enzyme immobilisation onto different carriers. Such immobilisation can make enzymes more stable, less antigenic and impart a longer circulation lifetime in the organism. This present contribution reviews the data on natural and synthetic carriers used for enzyme immobilisation, chemistry of enzyme binding, in vitro and in vivo properties of immobilised enzymes as well as their clinical use. Immobilised enzymes can be used as drugs for either local or systemic application (including soluble and insoluble immobilised enzymes for thrombolytic therapy, and for the treatment of both malignant diseases and some in-born enzyme deficiences). Immobilised enzymes can be also used for preparation of artificial cells (based on semipermeable microcapsules, liposomes, cells and cell ghosts). Special attention is paid to the problem of using the immobilisation principles for the construction of drug targeting systems (vector protein and antibody immobilisation, enzyme-polymer-vector conjugates, etc.).

Evaluation of a rapid method for determination of total urinary estrogens in morning samples from normally menstruating women

Total urinary estrogens (TUE) in morning urine samples delivered during seven days around midcycle from 14 normally menstruating women were analyzed and the results were compared with those obtained by radioimmunoassay of serum estradiol-17β (E 2) and LH. The Spinnbarkeit of the cervical mucus was also determined daily and ovulation was confirmed by RIA of serum progesterone. Significant correlations (p<0.01) between day of peak levels of serum E 2 and the day with the highest TUE value were obtained. Peak values for Spinnbarkeit, estradiol, TUE and LH were on the average obtained on cycle day 13.1 (10–17), 13.3 (10–16), 13.9 (11–18) and 14.1 (11–17), respectively, and the mean cycle length was 27.9 (24–32) days. The difference in mean peak day for estradiol and TUE, estradiol and Spinnbarkeit, estradiol and LH was significant in each comparison (p<0.01). Assays of TUE in morning samples as compared to analysis of TUE in 24 h urine portions were compared during 48 h in 10 women. The day with the highest TUE excretion was found to be the same in 7 women irrespective of the type of urinary sample analyzed. Analysis of urinary creatinine did not improve the TUE results. Levels of TUE in normally cycling females (n=14), in women taking contraceptive steroids (n=10), in menopausal women (n=10) and in normal men (n=10) agreed with those previously reported. It is concluded that the TUE determination by RIA may be helpful as a rapid method for everyday clinical use.

Demineralization of the finger bones in rheumatoid arthritis: a comparative study between visual estimation and bone density values determined by the silver method.

SummaryDeformities of the fingers, changes of the soft parts, erosions and uneven demineralization render the determination of bone density in the finger bones unreliable in rheumatoid arthritis. Moreover, the roentgenologic methods for bone density determinations demand a specialized radiographic technique and are time-consuming and expensive.The visual assessment of the demineralization grade, even though very approximate, is more valuable, if it is expressed as a figure and not as an indefinite statement. The use of a set of standard bones and the adoption of the direct radiographic enlargement technique is advocated by the writers as an aid for visual estimation. At the present stage of investigation, it seems to be the best method for everyday clinical use.

Advantages and limitations of the 0.3-mm. focal spot tube for magnification and other technics.

During the past several years a number of reports have attested to the value of the ultra-fine focal spot in diagnostic radiology. The technics are difficult, however, and still not in general use (1-5). In the course of four years experience with 0.3-mm. focal spot tubes we have had occasion to analyze the factors involved and adapt technics for everyday clinical use. Theoretical and Experimental Evaluation The size of the focal spot affects radiographic sharpness in so far as it directly affects penumbra size. Blurring due to this factor is determined by the relative sizes of the penumbra and the radiographic image. With decrease of the focal spot-object distance and/or increase of the object-film distance, both radiographic image and penumbra are magnified, but not in the same degree. The size of the penumbra is determined only by the relative distances involved and the focal spot size, and is independent of the size of object. With magnification, the penumbra size increases more rapidly than the image size. The practical limit to useful magnification is a little over three times, beyond which finer bony detail is lost. Figure 1 shows the relative sizes of images and penumbrae with 0.3-mm. and 1.0-mm. focal spots, with magnifications up to three times. It is evident in this example that relative penumbra sizes with the ultra-fine focal spot are smaller with magnification than with the larger focal spot without magnification. Magnification is obviously impractical with a 1.0-mm. focal spot or larger. It is also clear that, regardless of focal spot size, the relative penumbra size is minimum with the least possible degree of magnification. In our experience, however, the maximum radiographic detail is obtained with magnifications of about head of the radius picked up with magnification of 1 1/4 but not seen on multiple non-magnified films. The thickness of the upper portion of the fracture line suggests that its size without magnification was less than the defining power of the film. Of far more importance than the overall degree of magnification is the relative magnification that can be obtained. Figure 3 shows films of three strips of wire screening at levels 1, 2 and 3, at distances of 2 1/4, 4 1/2, and 6 3/4 inches, respectively, from the table top. The three exposures were made with focal spot-table top distances of 40, 20, and 20 inches, and with table top-film distances of 0, 20 and 30 inches, respectively. In the first film, where the strips overlap, it is almost impossible to differentiate the three levels. In the second film, the three levels can be distinguished, and in the last film the differential magnification or perspective of the three levels is readily appreciated. With the increased magnification, the screening at level 3 is magnified 34 per cent more than that at level 1.