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.

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.

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.

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.

The safety and efficacy of cisatracurium 0.15 mg.kg(-1) during nitrous oxide-opioid anaesthesia in infants and children.

We studied the neuromuscular and cardiovascular effects of a single, rapidly administered intravenous dose of cisatracurium 0.15 mg.kg(-1) in 27 infants (aged 1-23 months) and 24 children (aged 2-12.5 years). After midazolam premedication, anaesthesia was induced and maintained with thiopental and alfentanil in addition to nitrous oxide in oxygen. Neuromuscular function was monitored by evoked adductor pollicis electromyography. At least 15 min after intubation, each patient received cisatracurium 0.15 mg.kg(-1) over 5 s. Complete neuromuscular blockade was produced by this dose in all but one infant. The mean (SD) onset time of maximal blockade was more rapid in infants [2.0 (0.8) min] than in children [3.0 (1.2) min], p = 0. 0011. The clinical duration of action of cisatracurium (recovery of evoked response to 25% of control) was significantly longer in infants [43.3 (6.2) min] than in children [36.0 (5.4) min], p < 0.0001. Once neuromuscular function started to recover, the rate of recovery was similar in both age groups. Changes in blood pressure and heart rate after the administration of cisatracurium were negligible in both age groups. Cisatracurium, at a dose of 0.15 mg. kg(-1), was effective and well tolerated in infants and children.

A dose-ranging study of rapacuronium in pediatric patients.

BACKGROUND: The aim of this study was to determine the dose or doses of the new rapid-onset, short-acting, neuromuscular blocking drug rapacuronium that would provide satisfactory conditions for tracheal intubation at 60 s in infants and children. METHODS: Sixty-five infants (< 1 yr), 51 younger children (1-6 yr), and 49 older children (7-12 yr) were studied. Anesthesia was induced with thiopental-nitrous oxide-oxygen. Tracheal intubation was attempted 60 s after administration of one of five doses of rapacuronium (0.5, 1.0, 1.5, 2.0, or 2.5 mg/kg) and intubating conditions were assessed using a four-point scale. Following tracheal intubation, anesthesia was maintained with nitrous oxide-oxygen and alfentanil (12.5-50 microg/kg) as necessary. Neuromuscular transmission was monitored in an uncalibrated fashion using an acceleromyograph. RESULTS: Intubating conditions were good or excellent at 60 s in all infants after doses of 1.5 mg/kg or more and in all younger and older children after doses of 2.0 mg/kg or more. The duration of action of rapacuronium was dose- and age-dependent. Mean times to reappearance of the third twitch of the train-of-four (TOF; T3) were less than 10 min in infants at doses of 1.5 mg/kg or less and in younger and older children at doses of 2.0 mg/kg or less. Recovery of T3 after 1.0-2.0 mg/kg rapacuronium was significantly slower in infants compared with younger (P = 0.001) and older (P = 0.02) children. Five adverse experiences were related to rapacuronium administration: Bronchospasm (two instances), tachycardia (one instance), and increased salivation (two instances). None were serious. CONCLUSIONS: Doses of 1.5 and 2.0 mg/kg rapacuronium can produce satisfactory intubating conditions at 60 s in anesthetized infants and children, respectively, and are associated with a short duration of action.

Effective time to satisfactory intubation conditions after administration of rocuronium in adults. Comparison of propofol and thiopentone for rapid sequence induction of anaesthesia.

We determined the effective time to satisfactory intubation conditions after the administration of rocuronium 0.6 mg.kg-1 to 120 unpremedicated adult patients anaesthetised with propofol 2.5 mg.kg-1 or thiopentone 5 mg.kg-1. Intubation conditions were assessed in 10 subgroups of 12 patients at 30, 40, 50, 60 and 70 s. The effective times to satisfactory intubation conditions in 50 and 90% of patients were obtained by the method of maximum likelihood after log time-probit response transformations. Intubation conditions after induction of anaesthesia with propofol were satisfactory in 5/12 patients at 30 s, 7/12 at 40 s, 10/12 at 50 s, 11/12 at 60 s and 11/12 at 70 s compared with 1/12 patients at 30 s, 2/12 at 40 s, 5/12 at 50 s, 7/12 at 60 s and 8/12 at 70 s after induction with thiopentone. The effective times to satisfactory intubation conditions in 50% and 90% (95% confidence intervals) of patients after rocuronium 0.6 mg.kg-1 were 34 (26-40) s and 61 (50-81) s in patients given propofol compared with 57 (48-69) s and 101 (79-167) s in patients given thiopentone. We conclude that rocuronium 0.6 mg.kg-1 may be a suitable alternative to suxamethonium during rapid sequence induction of anaesthesia with propofol in situations where suxamethonium is contraindicated.