Ultra-high resolution array painting facilitates breakpoint sequencing.

OBJECTIVE: To describe a considerably advanced method of array painting, which allows the rapid, ultra-high resolution mapping of translocation breakpoints such that rearrangement junction fragments can be amplified directly and sequenced. METHOD: Ultra-high resolution array painting involves the hybridisation of probes generated by the amplification of small numbers of flow-sorted derivative chromosomes to oligonucleotide arrays designed to tile breakpoint regions at extremely high resolution. RESULTS AND DISCUSSION: How ultra-high resolution array painting of four balanced translocation cases rapidly and efficiently maps breakpoints to a point where junction fragments can be amplified easily and sequenced is demonstrated. With this new development, breakpoints can be mapped using just two array experiments: the first using whole-genome array painting to tiling resolution large insert clone arrays, the second using ultra-high-resolution oligonucleotide arrays targeted to the breakpoint regions. In this way, breakpoints can be mapped and then sequenced in a few weeks.

An investigation of language used by children to describe discomfort during dental pulp-testing.

AIM: Studies of the descriptions of pain by children have neglected their linguistic development, therefore estimates of dental pain in children may not be accurate. This study sought (1) to identify words chosen by children to describe dental pain and (2) to establish the effect of linguistic development on that description. SAMPLE: Seventy-eight consecutive children between the ages of 5 and 13 years attending a paediatric dental clinic. METHOD: Each child completed the WORD reading comprehension test. They then underwent a pulp test and a simulated pulp test, administered by a dentist in a counterbalanced order, of a healthy primary canine or permanent incisor, according to the child's age. To describe each test, the children had to (1) select words from a list of 58 read by the experimenter and (2) give ratings on scales representing 'sore' and 'tingly'. RESULTS: Analysis of variance confirmed that the children chose more words for the pulp test than for the simulated test (P < 0.001); the former also elicited higher ratings for 'sore' and 'tingly'. The numbers of words chosen were transformed by a square root constant to ensure a normal distribution. Multiple regression analysis then showed that (1) the better the children's reading comprehension, the fewer words they chose, possibly because they were less inclined to choose unfamiliar words, and (2) the older they were, the more words they chose, possibly because of having more experience of pain. There were similar findings for ratings of 'sore' and 'tingly'. CONCLUSIONS: To assess children's experience of pain (1) they need to be presented with a list of words like the ones in this study, (2) the numbers of words chosen by them would represent the severity of pain, and (3) those numbers need to be adjusted for the children's reading comprehension and age.

Digoxin and mortality in chronic heart failure. UK Heart Investigation.

Data from recent clinical trials suggest digoxin is now widely used in patients with chronic heart failure in sinus rhythm. We present data from a heart failure registry that reiterates concerns about the safety of digoxin in this population.

The relationship between QT intervals and mortality in ambulant patients with chronic heart failure. The united kingdom heart failure evaluation and assessment of risk trial (UK-HEART)

AIMS: Mortality in patients with heart failure remains high and is difficult to predict. QT interval parameters on a 12-lead ECG have been shown to predict arrhythmic events in patients with a variety of myocardial diseases. There is some, but not consistent, evidence that QT interval parameters may act as predictors of mortality, in particular sudden death, in patients with heart failure. In an adequately powered prospective study we have studied QT interval parameters in patients with stable chronic heart failure in order to determine whether they are predictive of all-cause mortality or mode of death. METHODS AND RESULTS: Five hundred and fifty-four ambulant outpatients with chronic heart failure were recruited. A 12-lead ECG, chest radiograph, echocardiogram, 24 h ambulatory electrocardiogram and serum for biochemical analysis were obtained at baseline. Patients were followed for 471+/-168 days. QT intervals were measured in all leads blinded to patient's characteristics and outcome, were corrected for heart rate, and the maximum QT intervals, and QT dispersion (range of QT intervals) were determined. The same parameters were determined for JT intervals. The primary end-point was all-cause mortality, secondary end-points were sudden cardiac death and death due to progressive heart failure. Multivariate analysis with the Cox's proportional hazards model was used to determine which variables were independently related to outcome. Four hundred and ninety-five patients had analysable ECGs at study entry and of these 71 died during follow-up. The heart rate corrected QT dispersion and maximum QT interval were significant univariate predictors of all-cause mortality (P=0.026 and <0.0001 respectively), and also of sudden death and progressive heart failure death, but were not related to outcome in the multivariate analysis. The independent predictors of all-cause mortality were cardiothoracic ratio (P=0.0003), creatinine (P=0.0009), heart rate (P=0.007), echocardiographically derived left ventricular end-diastolic dimension (P=0.007) and ventricular couplets on 24 h electrocardiographic monitoring (P=0.015). CONCLUSION: In an adequately powered prospective study none of the QT or JT parameters were shown to be independent predictors of outcome in patients with mild to moderate congestive heart failure. These variables do not therefore add to the prognostic information which can be gained from simple radiographic, biochemical, echocardiographic and Holter data in this group of patients.

QT dispersion as a predictor of long-term mortality in patients with acute myocardial infarction and clinical evidence of heart failure.

BACKGROUND: QT interval dispersion is a marker of inhomogeneous ventricular repolarization, and therefore has the potential to predict re-entry arrhythmias. Following acute myocardial infarction, increased QT dispersion has been associated with a higher risk of ventricular arrhythmias. However, whether or not QT dispersion predicts prognosis post-acute myocardial infarction is not clear. We addressed this issue by analysing the AIREX study registry. METHODS: AIREX was a follow-up study of 603 post-acute myocardial infarction patients who exhibited clinical signs of heart failure and were randomly allocated to ramipril or placebo. An interpretable 12-lead ECG obtained between day 0 and day 9 after the index infarction (median time 2 days) was available in 501 patients. We examined whether QT dispersion was a predictor of all-cause mortality in the AIREX study registry (mean follow-up 6 years). RESULTS: QT dispersion measurements were significantly increased in patients who subsequently died (QT dispersion: 92.0 +/- 38.5 ms vs 82.7 +/- 34.3 ins. P=0.005; rate corrected QT dispersion: 105.7 +/- 42.7 ms vs 93.1 +/- 35.9 ms, P<0.001). Univariate analysis showed that QT dispersion as a predictor of all-cause mortality risk (QT dispersion: hazard ratio per l0 ms 1.05, [95% CI 1.02 to 1.09]. P= 0.004; rate corrected QT dispersion: 1-07 [1.03 to 1.10], P<0.001): an increase of 10 ms added a 5-7%, relative risk of death. QT dispersion remained an independent predictor of all-cause mortality risk on multivariate analysis (QT dispersion: 1.05 [1.01 to 1.09], P=0.027; rate corrected QT dispersion: 1.05 [1.01 to 1.09]. P=0.022). CONCLUSION: QT dispersion. measured from Li routine 12-lead ECG following acute myocardial infarction complicated by heart failure provides independent information regarding the probability of long-term survival. However. the low sensitivity of this electrocardiographic marker limits its usefulness for risk stratification if used in isolation.

Ramipril reduces QT dispersion in patients with acute myocardial infarction and heart failure.

In a cohort of 67 patients from the Acute Infarction Ramipril Efficacy study, we showed that ramipril therapy was associated with a significant reduction in QT dispersion over a 2-month period after acute myocardial infarction. This reduction of ventricular repolarization inhomogeneity indicates an antiarrhythmic effect and may be an important additional mechanism for the reduced all-cause mortality and sudden death incidence achieved with angiotensin-converting enzyme inhibition after acute myocardial infarction.

Prospective study of heart rate variability and mortality in chronic heart failure: results of the United Kingdom heart failure evaluation and assessment of risk trial (UK-heart).

BACKGROUND: Patients with chronic heart failure (CHF) have a continuing high mortality. Autonomic dysfunction may play an important role in the pathophysiology of cardiac death in CHF. UK-HEART examined the value of heart rate variability (HRV) measures as independent predictors of death in CHF. METHODS AND RESULTS: In a prospective study powered for mortality, we recruited 433 outpatients 62+/-9.6 years old with CHF (NYHA functional class I to III; mean ejection fraction, 0.41+/-0.17). Time-domain HRV indices and conventional prognostic indicators were related to death by multivariate analysis. During 482+/-161 days of follow-up, cardiothoracic ratio, SDNN, left ventricular end-systolic diameter, and serum sodium were significant predictors of all-cause mortality. The risk ratio for a 41.2-ms decrease in SDNN was 1.62 (95% CI, 1.16 to 2.44). The annual mortality rate for the study population in SDNN subgroups was 5.5% for >100 ms, 12.7% for 50 to 100 ms, and 51.4% for <50 ms. SDNN, creatinine, and serum sodium were related to progressive heart failure death. Cardiothoracic ratio, left ventricular end-diastolic diameter, the presence of nonsustained ventricular tachycardia, and serum potassium were related to sudden cardiac death. A reduction in SDNN was the most powerful predictor of the risk of death due to progressive heart failure. CONCLUSIONS: CHF is associated with autonomic dysfunction, which can be quantified by measuring HRV. A reduction in SDNN identifies patients at high risk of death and is a better predictor of death due to progressive heart failure than other conventional clinical measurements. High-risk subgroups identified by this measurement are candidates for additional therapy after prescription of an ACE inhibitor.

Junior doctors and clinical audit.

OBJECTIVES: To assess the extent of junior doctor involvement in clinical audit, the degree of support from audit staff, and the perceived value of the resulting audits. DESIGN: Postal survey of National Health Service (NHS) junior doctors. SUBJECTS AND SETTINGS: 704 junior doctors in central Leeds hospitals, June 1996. RESULTS: Questionnaires were returned by 232 respondents (33%), 211 (31%) were completed; 157 respondents (74%) had personally performed audit. Mean (+/- SD) duration since last audit project was 14.9 (14.1) (range 0-84) months. Of the respondents who had personally performed audit, 88 (56%) did not use the hospital audit department, 60 (38%) received no guidance and only 19 (12%) were involved in re-auditing the same project. Mean (+/- SD) time spent per audit project was 27.8 (37.7), (range 2-212) hours. Seventy-five junior doctors (48%) were aware of subsequent change in clinical practice, 41 (26%) perceived a negative personal benefit from audit, 33 (21%) perceived a negative departmental benefit, and 42 (27%) felt that audit was a waste of time. CONCLUSIONS: A large proportion of junior doctors are involved in audit projects that do not conform to established good practice and which have a low impact on clinical behaviour. Although junior doctors feel that there is inadequate assistance and poor supervision whilst performing audit, they still support the principle of audit. There is a need to improve the quality and supervision of audit projects performed by junior doctors.

A partial double-blind, placebo-controlled study of electronic dental anaesthesia in children.

This study was carried out to determine the effectiveness of electronic dental anaesthesia (EDA) in restorative dental treatment for children. Thirty children were allocated at random to three groups to receive either EDA, a placebo-EDA or anaesthesia by oral injection. One dentist, having introduced and administered these procedures, completed an occlusal restoration in a maxillary permanent first molar in each child. The results showed that the children changed the EDA controls in accordance with pain assessed by their reports and by their facial signs counted in video records by an observer. Both the children and the observer were 'blind' to the difference between EDA and placebo-EDA. There were no statistical differences in: (1) the number of additional oral injections required in all groups to complete treatment, (2) the depth of cavity prepared, (3) the frequency of disruptive activities, (4) the dentist's management behaviour, (5) the dentist's rating of the children's disruptiveness, (6) pain estimated by the children's reports and by facial signs. Treatment time was shortest in the oral injection group, but had no significant correlation with any measure of pain, disruptive behaviour or depth of cavity. It was concluded that EDA was no less effective than anaesthesia administered by injection but, being no more effective than a placebo-EDA, probably worked by distracting the patients.

The Modified Dental Anxiety Scale: validation and United Kingdom norms.

The Corah Dental Anxiety Scale (CDAS) has been used extensively in epidemiology and clinical research. It is brief and is claimed to have good psychometric properties. However, it does not include any reference to local anaesthetic injections, a major focus of anxiety for many. Also, the multiple choice answers for three of the four questions are not clearly in order of severity of anxiety as the CDAS intends. The answers differ among the questions thus making them difficult to compare. They include descriptions of physiological reactions and anxiety, confusing two loosely related components of the experience. The Modified Dental Anxiety Scale (MDAS) described, added a question on anxiety about oral injections. New multiple choice answers, in clear order of anxiety and the same for each question, were provided. Twenty five dental personnel all confirmed independently the order of the multiple choice answers for the MDAS. They disagreed among themselves however, about the appropriate sequence for the answers denoting intermediate anxiety in the CDAS. Therefore the CDAS, unlike the MDAS, can provide meaningful measures only of extremely high or extremely low dental anxiety. Of 1392 subjects tested, 13 per cent expressed extreme anxiety about injections on the MDAS but were only 'fairly' or less anxious about drilling. Thus, the CDAS, unlike the MDAS, must overlook subjects very afraid of injections only. Data confirm the high reliability and validity of the MDAS and provide norms for phobic and nonphobic subjects.

Implementing universal precautions against infection.

As noted recently in the Journal, a small number of dentists, according to their own reports, do not always wear protective clothing such as gloves and a mask in treating their patients. The profession's recommendations for infection control have thus not been observed. The following describes some of the influences on the decisions taken by dentists to take or neglect these measures.

Children's expectations and recollections of discomfort associated with dental treatment.

It has been reported that adults, especially those most anxious about dentistry, expect more discomfort than they actually experience during treatment, and that, months after conservative treatment, they describe that experience as more uncomfortable than they had done immediately after treatment. This study sought to determine whether children's expectations and recollections of their discomfort are distorted in this way. Thirty-four children were asked to estimate, using a standard rating-scale, the degree of discomfort, if any, which they expected to experience in the dental treatment that was to follow. Immediately after treatment, which involved injection of local anaesthetic and preparation of a cavity, the children were asked to rate the degree of discomfort which they had just experienced. Six weeks and three months later, the children were sent an identical rating-scale and asked to record, under the supervision of their parents, the degree of discomfort which they recalled having experienced during that treatment. Like adults, the children experienced less discomfort during treatment than they had expected. Unlike adults, even the most anxious children recalled, 6 weeks and 3 months later, no more discomfort than they had reported immediately after treatment. Nevertheless, the unrealistic expectations of discomfort by children should be a prominent target for behavioural management by dentists.