Practical guide to the Idea, Development and Exploration stages of the IDEAL Framework and Recommendations.

BACKGROUND: Evaluation of new surgical procedures is a complex process challenged by evolution of technique, operator learning curves, the possibility of variable procedural quality, and strong treatment preferences among patients and clinicians. Preliminary studies that address these issues are needed to prepare for a successful randomized trial. The IDEAL (Idea, Development, Exploration, Assessment and Long-term follow-up) Framework and Recommendations provide an integrated step-by-step evaluation pathway that can help investigators achieve this. METHODS: A practical guide was developed for investigators evaluating new surgical interventions in the earlier phases before a randomized trial (corresponding to stages 1, 2a and 2b of the IDEAL Framework). The examples and practical tips included were chosen and agreed upon by consensus among authors with experience either in designing and conducting IDEAL format studies, or in helping others to design such studies. They address the most common challenges encountered by authors attempting to follow the IDEAL Recommendations. RESULTS: A decision aid has been created to help identify the IDEAL stage of an innovation from literature reports, with advice on how to design and report the IDEAL study formats discussed, along with the ethical and scientific rationale for specific recommendations. CONCLUSION: The guide helps readers and researchers to understand and implement the IDEAL Framework and Recommendations to improve the quality of evidence supporting surgical innovation.

Menstrual cycle effects on hypothalamic dopamine receptor function in women with a history of puerperal bipolar disorder.

Neuroendocrine challenge tests of hypothalamic dopamine receptor function in the early postpartum period suggest that the sensitivity of these receptors is increased in women with a history of bipolar disorder after childbirth. We tested the hypothesis that, in women predisposed to bipolar disorder in the puerperium, hypothalamic dopamine receptor function is more sensitive to changes in circulating ovarian hormone concentrations than in women without such histories. Eight fully recovered and drug-free women who had had at least one episode of bipolar illness following childbirth were compared with nine normal controls. Growth hormone (GH) responses to apomorphine (APO 0.005 mg s.c.) were measured in the early follicular phase, when plasma concentrations of ovarian hormones are low, and in the mid-luteal phase, when they are relatively high. The recovered bipolar subjects and the controls did not differ from each other in their follicular and midluteal oestrogen and progesterone concentrations. In the midluteal phase, both groups had increased oestrogen and progesterone levels. The recovered bipolar subjects did not differ from controls in baseline concentrations of GH in either of the menstrual phases. The APO-GH responses of the two groups did not differ in the follicular phase, but in the midluteal phase, when female sex steroids are relatively increased, the recovered group had significantly enhanced APO-GH responses [MANOVA for repeated measures: (i) area under the curve, group by phase effect: p < 0.04; (ii) GH peak rise after APO, group by phase effect: p < 0.056] and the responses were not related to concurrent measures of mood. The results of this small study of women predisposed to bipolar disorder in the puerperium shows an increased dopaminergic receptor sensitivity in the luteal phase of the menstrual cycle. It suggests that their dopaminergic systems have increased sensitivity to changes in circulating female sex steroids. This may be aetiologically relevant to the pathogenesis of puerperal bipolar disorder.

External quality assessment of techniques for the detection of drugs of abuse in urine.

Five chromatographic and six immunoassay techniques were compared using data reported by 131 participants in the UK National External Quality Assessment Scheme for Drugs of Abuse in Urine. Twenty five samples were studied containing none or one of three concentrations of amphetamine, barbiturates, benzodiazepines, benzoylecgonine, methadone and morphine. Technique sensitivity and specificity achieved with realistic clinical samples of 25 mL vol were assessed as the percentage of true positive and true negative tests, respectively. Thin-layer chromatography was inadequate for the detection of several analytes, the sensitivity for 0.5 mg/L of benzoylecgonine being < 30%, and for 1.5 mg/L of amphetamine < 86%. Gas chromatography with mass spectrometry was significantly less sensitive than other techniques for the detection of 0.5 mg/L of benzoylecgonine (71%) and 1.5 mg/L of morphine (88%). High-performance liquid chromatography was the most sensitive for amphetamine. Immunoassays performed well when operating above their specified cut-off concentrations but, because they are directed to quinalbarbitone showed reduced cross-reactivity with amylobarbitone, the barbiturate more commonly prescribed in the UK.

A blood spot assay for apo A1 and B lipoproteins and the apo B/A1 ratio.

A study of conditions for the elution of apo A1 and B lipoproteins from dried blood spots has led to the development of an apo B/A1 ratio assay with results for dried blood spots which are comparable with serum assays. This assay has been developed to be suitable for large scale population screening. The concept of measuring ratios for co-eluting blood constituents improves the accuracy and precision of blood spot assays and opens up the possibility that patients could take their own blood sample and send it to the laboratory by post.

Increased sensitivity of dopamine receptors and recurrence of affective psychosis after childbirth.

OBJECTIVE: To test the hypothesis that affective psychosis after childbirth is associated with an altered sensitivity to dopaminergic stimulation. DESIGN: Prospective study of pregnant women at high risk of developing an affective psychosis after childbirth. Clinical assessments in pregnancy and after delivery were made by using a semistructured interview (schedule for affective disorders and schizophrenia) and psychiatric illnesses were categorised according to operational criteria (research diagnostic criteria). SETTING: Obstetric and psychiatric departments in and around Greater London. SUBJECTS: 29 pregnant women with a history of bipolar or schizoaffective psychosis and 47 control pregnant women. Of these, 16 from each group participated in a growth hormone challenge test and the results for 15 women in each group were analysed. INTERVENTIONS: On the fourth day postpartum women participating in the hormone challenge test were given a subcutaneous injection of a small dose (0.005 mg/kg) of the dopamine agonist apomorphine. MAIN OUTCOME MEASURES: Growth hormone secretion in response to apomorphine as an index of the functional state of hypothalamic dopamine receptors. RESULTS: Eight of the 15 women at risk of psychosis subsequently had a recurrence of illness (five bipolar, one schizomanic, and two major depressive illnesses); these women had significantly greater growth hormone responses to apomorphine than the seven at risk women who remained well and the 15 controls, and there were no significant differences between groups in average baseline growth hormone concentrations. The mean (SD) concentrations for women with recurrence, women at risk who remained well, and control women respectively were: average baseline concentrations 1.06 (1.14), 1.44 (1.39), and 0.90 (1.34) mU/l; peak increase in concentrations 13.68 (12.95), 3.46 (4.68), and 3.40 (3.83) mU/l (between group difference p less than 0.05); average increase in concentrations 6.74 (7.01), 1.78 (3.39), and 1.40 (2.05) mU/l (p less than 0.05). CONCLUSIONS: The onset of affective psychosis after childbirth was associated with increased sensitivity of dopamine receptors in the hypothalamus and possibly elsewhere in the brain. Such changes may be triggered by the sharp fall in circulating oestrogen concentrations after delivery.

Electrodes in clinical chemistry.

On theoretical grounds it would appear preferable to use calibrants which are not adjusted to a constant ionic strength, whether concentration or activity is being estimated directly. For indirect methods, when sample and calibrant are diluted in an ionic strength adjusting buffer, there is probably little difference between adjusted and unadjusted calibrants. In this case a simple calculation of concentration is possible. A simple algorithm may be used for activity estimation. The algorithm for direct concentration estimation is more complex. If concentration, rather than activity, is required an indirect method must be used. If activity is required a direct method must be used. The quantitative effects of variations in calibration procedure may be smaller than variations in junction potential.

A data processing system for a group of three clinical chemistry laboratories. 1. Hardware and organisation.

A real time data processing system for a group of three clinical chemistry laboratories (one base and two satellite) has been developed as a successor to one used previously. This paper describes both the inadequacies of the previous worksheet-based system and the advantages of the new system, including flexibility, fast response and comprehensiveness, incorporating urgent routine and long delay (that is, endocrine) requests, and the use of a parallel flow work scheme.

A data processing system for a group of three clinical chemistry laboratories. 2. File structure and operation.

In the preceding article the hardware and organisation of a new data processing system were described. This paper deals with the file structure and operation, the use of management information, the economical use of disc-file space and hardware, and the transferability of the system.

Development and evaluation of a six-channel automated analyser for 24-h urine specimens.

A system has been developed for the analysis of 24-h urine collections for sodium, potassium, calcium, phosphate, urea, and creatinine, using a six channel AutoAnalyzer for the analysis,and a computer for calculating the results and producing cumulative reports.

Implementation of a British computer system for laboratory data handling.

This paper describes the development and implementation of a small real-time British computer system for the handling of patient and test result data in the chemical pathology laboratories of the King's Health District (Teaching). Work destined for subsequent reporting by the computer system is entered by continuous on-line teletype. Test result data from multichannel analyzers are input using an on-line trace reader. Cumulative reports are printed both by line printer at the central laboratory and by on-line teletypes at two peripheral hospital laboratories. In a working day over 4000 new items of data are generated and 300-500 reports printed. The use of a trace reader as an inputing device and the method of employing a high capacity disk to give both speed of operation and limited archive facility are discussed.