An economic evaluation of the randomized controlled trial of topical corticosteroid and home-based narrowband ultraviolet B for active and limited vitiligo (the HI-Light Vitiligo Trial).

BACKGROUND: Economic evidence for vitiligo treatments is absent. OBJECTIVES: To determine the cost-effectiveness of (i) handheld narrowband ultraviolet B (NB-UVB) and (ii) a combination of topical corticosteroid (TCS) and NB-UVB compared with TCS alone for localized vitiligo. METHODS: Cost-effectiveness analysis alongside a pragmatic, three-arm, placebo-controlled randomized controlled trial with 9 months' treatment. In total 517 adults and children (aged ≥ 5 years) with active vitiligo affecting < 10% of skin were recruited from secondary care and the community and were randomized 1: 1: 1 to receive TCS, NB-UVB or both. Cost per successful treatment (measured on the Vitiligo Noticeability Scale) was estimated. Secondary cost-utility analyses measured quality-adjusted life-years using the EuroQol 5 Dimensions 5 Levels for those aged ≥ 11 years and the Child Health Utility 9D for those aged 5 to < 18 years. The trial was registered with number ISRCTN17160087 on 8 January 2015. RESULTS: The mean ± SD cost per participant was £775 ± 83·7 for NB-UVB, £813 ± 111.4 for combination treatment and £600 ± 96·2 for TCS. In analyses adjusted for age and target patch location, the incremental difference in cost for combination treatment compared with TCS was £211 (95% confidence interval 188-235), corresponding to a risk difference of 10·9% (number needed to treat = 9). The incremental cost was £1932 per successful treatment. The incremental difference in cost for NB-UVB compared with TCS was £173 (95% confidence interval 151-196), with a risk difference of 5·2% (number needed to treat = 19). The incremental cost was £3336 per successful treatment. CONCLUSIONS: Combination treatment, compared with TCS alone, has a lower incremental cost per additional successful treatment than NB-UVB only. Combination treatment would be considered cost-effective if decision makers are willing to pay £1932 per additional treatment success.

Randomized controlled trial of topical corticosteroid and home-based narrowband ultraviolet B for active and limited vitiligo: results of the HI-Light Vitiligo Trial.

BACKGROUND: Evidence for the effectiveness of vitiligo treatments is limited. OBJECTIVES: To determine the effectiveness of (i) handheld narrowband UVB (NB-UVB) and (ii) a combination of potent topical corticosteroid (TCS) and NB-UVB, compared with TCS alone, for localized vitiligo. METHODS: A pragmatic, three-arm, placebo-controlled randomized controlled trial (9-month treatment, 12-month follow-up). Adults and children, recruited from secondary care and the community, aged ≥ 5 years and with active vitiligo affecting < 10% of skin, were randomized 1 : 1 : 1 to receive TCS (mometasone furoate 0·1% ointment + dummy NB-UVB), NB-UVB (NB-UVB + placebo TCS) or a combination (TCS + NB-UVB). TCS was applied once daily on alternating weeks; NB-UVB was administered on alternate days in escalating doses, adjusted for erythema. The primary outcome was treatment success at 9 months at a target patch assessed using the participant-reported Vitiligo Noticeability Scale, with multiple imputation for missing data. The trial was registered with number ISRCTN17160087 on 8 January 2015. RESULTS: In total 517 participants were randomized to TCS (n = 173), NB-UVB (n = 169) and combination (n = 175). Primary outcome data were available for 370 (72%) participants. The proportions with target patch treatment success were 17% (TCS), 22% (NB-UVB) and 27% (combination). Combination treatment was superior to TCS: adjusted between-group difference 10·9% (95% confidence interval 1·0%-20·9%; P = 0·032; number needed to treat = 10). NB-UVB alone was not superior to TCS: adjusted between-group difference 5·2% (95% CI - 4·4% to 14·9%; P = 0·29; number needed to treat = 19). Participants using interventions with ≥ 75% expected adherence were more likely to achieve treatment success, but the effects were lost once treatment stopped. Localized grade 3 or 4 erythema was reported in 62 (12%) participants (including three with dummy light). Skin thinning was reported in 13 (2·5%) participants (including one with placebo ointment). CONCLUSIONS: Combination treatment with home-based handheld NB-UVB plus TCS is likely to be superior to TCS alone for treatment of localized vitiligo. Combination treatment was relatively safe and well tolerated but was successful in only around one-quarter of participants.

Assessment of a rapid liquid-based cytology method for measuring sputum cell counts.

Differential sputum cell counting is not widely available despite proven clinical utility in the management of asthma. We compared eosinophil counts obtained using liquid-based cytology (LBC), a routine histopathological processing method, and the current standard method. Eosinophil counts obtained using LBC were a strong predictor of sputum eosinophilia (≥3%) determined by the standard method suggesting LBC could be used in the management of asthma.

The utility of exhaled nitric oxide in patients with suspected asthma.

The value of FENO measurements in patients with symptoms suggestive of asthma is unclear. We performed an observational study to assess the ability of FENO to diagnose asthma and to predict response to inhaled corticosteroids (ICS). Our findings suggest FENO is not useful for asthma diagnosis but is accurate at predicting ICS response.

Do investigator meetings improve recruitment rates in clinical trials? A retrospective before-and-after study of data from nine multi-centre clinical trials.

BACKGROUND: Poor recruitment in clinical trials is well-documented. In large, multi-centre trials, communication between the coordinating centre and trial sites is essential. A commonly used communication tool is the hosting of an investigator/collaborator meeting, which offers an opportunity for sites to re-train and receive trial updates, learn from each other, share best practice and troubleshoot issues. Anecdotally, there is a perception that recruitment rates may increase after holding such a meeting. The aim of this before-and-after study was to examine any changes in recruitment after an investigator meeting. METHODS: We conducted a retrospective study of nine trials at the Nottingham Clinical Trials Unit (NCTU) that were open to recruitment between 2014 and 2018. In the 8 weeks prior to the date of the investigator meeting, 82 sites (across nine trials) were open to recruitment; 60 of which attended the meeting, 22 who did not. Using meeting attendance data available in Trial Master Files (TMF) and recruitment data from randomisation datasets, we examined recruitment rates in the 8 weeks prior to and following the date of the investigator meeting. RESULTS: For the 82 sites included, 284 participants were recruited in the 8 weeks prior to the meeting, with a further 300 participants recruited in the 8 weeks post meeting. This gives a mean change in weekly recruitment of 0.073 (- 0.129, 0.275) per site, demonstrating no statistically significant increase in recruitment after the investigator meeting. For the 60 attending sites, recruitment increased from 254 participants prior to the meeting to 271 post meeting, giving a 0.100 (- 0.160, 0.360) mean change in weekly recruitment per site, providing no evidence that recruitment rates increase following an investigator meeting. CONCLUSION: There is no statistical evidence to conclude that holding an investigator meeting increases recruitment in the 8 weeks following the meeting. Thus, if the meeting has been held in the belief that it will have a positive impact upon recruitment, trialists may wish to consider other evidence-based strategies known to increase recruitment rates. However, since there are a variety of reasons why an investigator meeting may be held, trialists should continue to consider this as a communication strategy with sites.

Motivational influences on anaesthetists' use of practice guidelines.

BACKGROUND: With the proliferation of practice guidelines in anaesthesia comes the possibility that anaesthetists may, during the course of their work, commit 'violations' (actions that are not intended to cause harm to patients, but that deviate from guidelines). These may have a long-term impact on patient safety, and so there is a need to understand what makes anaesthetists decide to follow or deviate from guidelines. METHODS: A questionnaire on the use of guidelines was completed by 629 College Fellows. This presented three anaesthetic scenarios, each of which involved a deviation from a guideline, and asked respondents to rate their beliefs about the likely outcome of the violation, the level of social approval they would have for violating, the amount of control they would have over violating, and the practice of their peers with regard to violating. RESULTS: In all three scenarios, beliefs about the outcome of violating and the amount of control over violating predicted respondents' self-reported likelihood that they would commit the violation. In two scenarios, beliefs about the practice of peers predicted violating. Level of social approval predicted violating in one scenario only. CONCLUSIONS: Anaesthetists' decisions to follow or deviate from guidelines are influenced by the beliefs they hold about the consequences of their actions, the direct or indirect influence of others, and the presence of factors that encourage or facilitate particular courses of action.

Human factors in anaesthetic practice: insights from a task analysis.

BACKGROUND: Despite a growing recognition of the role of human error in anaesthesia, it remains unclear what should be done to mitigate its effects. We addressed this issue by using task analysis to create a systematic description of the behaviours that are involved during anaesthesia, which can be used as a framework for promoting good practice and highlight areas of concern. METHODS: The task steps involved in preparing and delivering anaesthesia were identified using hierarchical task analysis (HTA). The systematic human error reduction and prediction approach (SHERPA) was then used to identify potential human errors at each task step and suggest ways of preventing these errors. RESULTS: The number and type of behaviours involved vary according to the 'phase' of anaesthesia, with tasks in the induction room, including induction of anaesthesia itself, being the most demanding. Errors during preoperative planning and perioperative maintenance could be avoided by measures to support information handling and decision-making. Errors during machine checking, induction, and emergence could be reduced by streamlining or automating task steps, or by making changes to the physical design of the work environment. CONCLUSIONS: We have demonstrated the value of task analysis in improving anaesthetic practice. Task analysis facilitates the identification of relevant human factors issues and suggests ways in which these issues can be addressed. The output of the task analysis will be of use in focusing future interventions and research in this area.

The role of Bradyrhizobium japonicum nitric oxide reductase in nitric oxide detoxification in soya bean root nodules.

The identification of nitric oxide-bound leghaemoglobin within soya bean nodules has led to the question of how Bradyrhizobium japonicum bacteroids overcome the toxicity of this nitric oxide. It has previously been shown that one candidate for nitric oxide detoxification, the respiratory nitric oxide reductase, is expressed in soya bean nodules from plants supplied with nitrate. In this paper, the role of this enzyme in nitric oxide detoxification is assessed and discussion is provided on other possible B. japonicum nitric oxide detoxification systems.

Muscle relaxants in paediatric day case surgery.

It has been estimated that more than 60% of all paediatric surgery is performed on a day case basis. The benefits of this type of surgery in children include reduced costs, avoidance of the stress of hospitalization and less disruption to family life. The growth of day surgery in children has been facilitated by the development of non-depolarizing neuromuscular blocking agents characterized by short and intermediate duration of action and fewer side-effects. The more rapid onset and shorter duration of action of non-depolarizing neuromuscular blocking agents in children should facilitate the use of these agents in place of succinylcholine for day case procedures.

Economics of low-flow anaesthesia in children.

We have measured the consumption of isoflurane and fresh gas flows in 77 infants and children during 20 all-day operating sessions using either the enclosed Mapleson A or the circle absorber mode of the Carden 'Ventmasta' ventilator. The average consumption (SD) of isoflurane in 37 patients anaesthetised using the A mode of the Carden system with a mean fresh gas flow of 2.61 min-1 was 11.1 (4.2) g.h-1, while that in 40 patients anaesthetised using the circle absorber mode with a mean fresh gas flow of 1.21 min-1 was 4.7 (1.0) g.h-1. These figures represent an overall saving of 58% in the use of isoflurane (p < 0.0001) and a mean reduction in fresh gas flow of 54% (p < 0.0001) as a result of using low-flow anaesthesia. With the addition of small bore breathing hoses the adult circle absorber system was practical to use in both infants and children. These findings should stimulate interest in the use of low-flow techniques in children.

Dose-response and minimum time to satisfactory intubation conditions after mivacurium in children.

We assessed neuromuscular blocking effects and tracheal intubation conditions following mivacurium in 121 anaesthetised children aged 1-10 years. The study was conducted in three parts. Parts 1 and 2 were undertaken during thiopentone-alfentanil-nitrous oxide anaesthesia; neuromuscular blockade was evaluated by recording the force of contraction of the adductor pollicis in response to train-of-four stimulation at 0.1 Hz. In part 1 the potency of mivacurium was determined in 15 children using a single dose-response technique; in part 2 onset and recovery times were determined in six children following a dose of mivacurium 0.2 mg.kg-1. In part 3 of the study, clinical intubation conditions were assessed in two groups of 50 children whose tracheas were intubated 60 or 90 s after injection of mivacurium 0.2 mg.kg-1 during thiopentone-nitrous oxide anaesthesia. The ED50 and ED95 of mivacurium were 54 and 105 micrograms.kg-1 respectively. The times to 90% and 100% depression of control twitch were 1.3 (0.3) and 1.9 (0.5) min; times to 5%, 25%, 75% and 90% recovery were 6.4 (1.0), 8.4 (1.1), 12.5 (1.1) and 14.4 (1.9) min, respectively. Intubation conditions were rated satisfactory in 33/50 children (0.66, 95% confidence interval 0.51-0.79) at 60 s and in 49/50 children (0.98, 95% confidence interval 0.89-1.0) at 90 s (p = 0.0001). Intubation conditions 90 s after mivacurium 0.2 mg.kg-1 were significantly better than those obtained in 10 patients given anaesthetic drugs alone (p = 0.002).

Oral midazolam compared with diazepam-droperidol and trimeprazine as premedicants in children.

Ninety children were assigned randomly to one of three groups for premedication with oral midazolam 0.5 mg.kg-1, diazepam 0.25 mg.kg-1 with droperidol 0.25 mg.kg-1, or trimeprazine 2 mg.kg-1. On arrival at the anaesthetic room, anxiolysis was satisfactory in 26 out of 29 (90%) children who received midazolam compared with 23 out of 29 (79%) who received diazepam-droperidol and 18 out of 29 (62%) who received trimeprazine (P < 0.05); at induction of anaesthesia these proportions were 24 out of 29 (83%), 16 out of 29 (55%) and 11 out of 29 (40%) respectively (P < 0.001). When individual groups were compared, anxiolysis was significantly greater in the midazolam group compared with the trimeprazine group on arrival in the anaesthetic room (P < 0.05) and significantly greater in the midazolam group than in either the diazepam-droperidol or the trimeprazine groups at induction of anaesthesia (P < 0.05 and P < 0.001 respectively). There were no significant differences in times to early recovery between the groups (25.4, 24.4 and 28.5 min). Analysis of behavioural questionnaires completed two weeks after hospitalization showed a trend towards fewer postoperative behavioural disturbances in children who received midazolam or diazepam-droperidol compared with trimeprazine (47 and 44% vs 75%); when the results for the benzodiazepine-containing premedicants were combined, the difference between these groups and trimeprazine was statistically significant (P < 0.05).

Nebulised adrenaline 1:1000 in the treatment of croup.

A case of infective croup is described which was successfully treated using nebulised adrenaline 1:1000. The diagnosis of croup and the basis for the use of nebulised adrenaline are discussed.

Use of the post-tetanic count to monitor recovery from intense neuromuscular blockade in children.

The post-tetanic count was investigated as a method of monitoring intense neuromuscular blockade in children. One of five myoneural blockers (atracurium, vecuronium, pancuronium, tubocurarine or alcuronium) was given to groups of six children during nitrous oxide-oxygen-halothane anaesthesia. During recovery, the first post-tetanic response always preceded the first train-of-four response. The interval between the appearance of the first post-tetanic response and the first train-of-four response was typically 5-10 min for the intermediate-acting agents vecuronium and atracurium, and 20-30 min for the long-acting agents pancuronium, alcuronium and tubocurarine. A post-tetanic count of 6 with alcuronium and tubocurarine, or 7 with vecuronium, atracurium and pancuronium indicated that recovery of the first train-of-four response was imminent.

Oral administration of midazolam as a premedicant for paediatric day-case anaesthesia.

Fifty-four children aged 1-10 years, scheduled for day-case anaesthesia were prescribed either oral midazolam 0.5 mg.kg-1 or a placebo preparation 30-60 min pre-operatively on a double-blind basis. On arrival at the induction room, anxiolysis was satisfactory in 23 out of 24 (96%) children who received midazolam compared with 12 out of 27 (44%) of those who received placebo (p < 0.001); at induction of anaesthesia these proportions were 21 out of 24 (88%) and nine out of 27 (33%) respectively (p < 0.001). The time to early recovery from anaesthesia was somewhat longer in children premedicated with midazolam compared with controls (28.2 vs 21.9 min) (p < 0.05). Similarly, the time to hospital discharge was longer in the midazolam group (244 vs 185 min) (p < 0.01). Analysis of behavioural questionnaires completed by parents 2 weeks after hospitalisation indicated that there were fewer postoperative behavioural disturbances in children premedicated with midazolam compared with controls (p < 0.05).

An evaluation of rebreathing with the bain system during anaesthesia with spontaneous ventilation.

Data from 12 anaesthetized patients breathing spontaneously from the Bain system were used to calculate the degree of rebreathing occurring when the fresh gas flowrate (VF) was equal to 2, 1 and 0.7 times the estimated normal minute ventilation (Vtot). Measurements of the expired minute volume (VE) and end-tidal carbon dioxide tension (PE'CO2) were made to determine the effects of this rebreathing. No rebreathing occurred when VF was equal to twice Vtot. When VF was equal to Vtot rebreathing was usually small in amount and produced no changes in VE or PE'CO2. Changes attributable to rebreathing occurred in only two patients when VF was reduced to 0.7 Vtot. These results are explained by the presence of anaesthesia-induced ventilatory depression and favourable changes occurring in the respiratory wave forms in the majority of patients studied. In some patients, greater values of VE and rebreathing occurred in response to strong surgical stimulation. The net result of increased ventilation in these patients was a decrease in PE'CO2. It is concluded that during anaesthesia, when the Bain system is used with VF equal to Vtot, any increase in PE'CO2 which may result from rebreathing is likely to be small and seldom of clinical importance.

Effects of fasting and oral premedication on the pH and volume of gastric aspirate in children.

The pH and volume of gastric aspirate were measured immediately after the induction of anaesthesia in 224 healthy children to determine the effects of decreasing the period of fasting and of giving oral premedicants before anaesthesia. Fasting for less than 4 h was found to increase the volume of gastric aspirate and the risk of developing pulmonary aspiration syndrome. Trimeprazine syrup was found to increase the pH of the gastric contents, and decrease the likelihood of the pulmonary aspiration syndrome. There was a significant increase in gastric volume in patients premedicated with temazepam elixir which did not occur in patients given temazepam capsules. These results support the custom of fasting patients for at least 4 h before anaesthesia and indicate that oral premedicants and their vehicles can have significant effects on the stomach.