Jennifer Freeman

SABRE: a multicentre randomised control trial of nebulised hypertonic saline in infants hospitalised with acute bronchiolitis

Aim Acute bronchiolitis is the commonest cause for hospitalisation in infancy. Supportive care remains the cornerstone of current management and no other therapy has been shown to influence the course of the disease. It has been suggested that adding nebulised hypertonic saline to usual care may shorten the duration of hospitalisation. To determine whether hypertonic saline does have beneficial effects we undertook an open, multi-centre parallel-group, pragmatic RCT in ten UK hospitals. Methods Infants admitted to hospital with a clinical diagnosis of acute bronchiolitis and requiring oxygen therapy were randomised to receive usual care alone or nebulised 3% hypertonic saline (HS) administered 6-hourly. Randomisation was within 4 h of admission. The primary outcome was time to being assessed as ‘fit’ for discharge with secondary outcomes including time to discharge, incidence of adverse events together with follow up to 28 days assessing patient centred health related outcomes. Results A total of 317 infants were recruited to the study. 158 infants were randomised to HS (141 analysed) and 159 to standard care (149 analysed). There was no difference between the two arms in time to being declared fit for discharge (hazard ratio: 0−95, 95% CI: 0.75−1.20) nor to actual discharge (hazard ratio: 0.97, 95% CI: 0.76−1.23). There was no difference in adverse events. One infant in the HS group developed bradycardia with desaturation. Conclusion This study does not support the use of nebulised HS in the treatment of acute bronchiolitis over usual care with minimal handlings. ClinicalTrials.gov registration number NCT01469845.

Computerised cognitive behavioural therapy for the treatment of depression in people with multiple sclerosis: external pilot trial

BackgroundPeople with multiple sclerosis (MS) are at high risk of depression. We undertook a pilot trial of computerised cognitive behavioural therapy (CCBT) for the treatment of depression in people with MS to test the feasibility of undertaking a full trial.MethodsParticipants with a diagnosis of MS and clinical levels of depression were recruited through out-patient clinics and postal screening questionnaires at two UK centres and randomised to CCBT or usual care. Clinical outcomes included the Beck Depression Inventory (BDI-II) and Multiple Sclerosis Impact Scale (MSIS-29) at baseline, 8 and 21 weeks. Feasibility outcomes included: recruitment rate; reasons for refusal, withdrawal and dropout; feasibility and acceptability of the proposed outcome measures; sample size estimation and variation in and preferences for service delivery.ResultsTwenty-four participants were recruited. The recruitment rate, calculated as the proportion of those invited to fill in a screening questionnaire who were consented into the trial, was 4.1%. Recruitment through out-patient clinics was somewhat slower than through screening questionnaire mail-out but the overall recruitment yield was similar. Of the 12 patients in the CCBT arm, 9 (75%) completed at least four, and 6 completed all 8 CCBT sessions. For completers, the median time (IQR) to complete all eight CCBT sessions was 15 (13 to 20) weeks. Participants expressed concern about the face validity of the Beck Depression Inventory II for the measurement of self-reported depression in people with MS. The MSIS-29 was the patient-reported outcome measure which participants felt best reflected their concerns. The estimated sample size for a full trial is between 180 and 390 participants. NHS partners were not delivering CCBT in community facilities and participants preferred to access CCBT at home, with no one expressing a preference for use of CCBT in an alternative location.ConclusionsA definitive trial, with a recruitment window of one year, would require the participation of around 13 MS centres. This number of centres could be reduced by expanding the eligibility criteria to include either other neurological conditions or people with more severe depression. The MSIS-29 should be used as a patient-important outcome measurement.Trial registrationISRCTN: ISRCTN81846800

Surface replacement trapeziometacarpal joint arthroplasty--early results.

This study reviews the results of Surface Replacement Trapeziometacarpal (SR TMC, Avanta®, San Diego, CA) total joint arthroplasty. Fifty patients (62 joints) were included in the study. Forty-three patients (54 joints) were seen at final follow up. Seven patients (eight joints) were interviewed over the phone. Seven patients were revised to trapeziectomy and ligament reconstruction with tendon interposition, five for aseptic loosening and two for dislocation. At final follow up, the mean Quick DASH score was 30.4 and the Sollerman Score was 77.3. Radiological review of the surviving 55 joints showed subsidence of four trapezial components in asymptomatic patients. Cumulative survival rate was 91% at 3 years. Eighty-five percent of the patients were satisfied with the outcome of their treatment.

Avascular necrosis in acute and acute-on-chronic slipped capital femoral epiphysis.

This study reviews the factors affecting the development of avascular necrosis (AVN) after slipped capital femoral epiphysis. Seventy-three patients (n=73) with ninety-two (n=92) hips were included in the study. Out of these 92, 16 were acute, 43 acute-on-chronic, 29 chronic, and four were preslips. Postoperative radiographs showed a reduction in 18 (19.5%) slips. The mean preoperative slip angle was 32° (range 9–76) compared with the postoperative slip angle of 29.9° (range 10–75°) (P=0.004). Four patients developed AVN. Our results showed that intraoperative reduction of the slip (P<0.001) was significantly related to the development of AVN and was also associated with poor functional outcome.

Esthetic judgments of palatally displaced canines 3 months postdebond after surgical exposure with either a closed or an open technique.

INTRODUCTION The aim of this study was to compare the esthetic judgments of orthodontists and laypeople regarding the appearance of palatally displaced canines 3 months after treatment with either a closed or an open surgical exposure and orthodontic alignment. METHODS A multicenter randomized controlled trial was undertaken in 3 hospitals in the United Kingdom. Patients with unilateral palatally displaced canines were randomly allocated to receive either a closed or an open surgical exposure. The teeth were aligned with fixed appliances, and 3 months after debond, intraoral photographs were taken. The photographs were projected in random order to 2 panels of judges (orthodontists and laypeople), who completed a questionnaire. RESULTS The images of 67 participants (closed, 33; open, 34) were included. The laypeople were able to identify the operated tooth only 49.7% of the time (95% CI, 45.3%-54.0%); this was no better than chance (P = 0.880). The orthodontists were more successful but still identified the treated canine with certainty only 60.7% of the time (95% CI, 53.7%-67.8%; P = 0.003). Both panels more frequently assessed the unoperated canine to have a better appearance than the contralateral operated canine; however, there were no differences between the closed and open groups (proportion preferring unoperated canine-laypeople: closed, 58.7%; open, 57.0%; P = 0.43; and orthodontists: closed, 60.9%; open, 60.6%; P = 0.27). CONCLUSIONS There is an esthetic impact to aligning a palatally displaced canine, but it is mostly minor and unlikely to be detectable by laypeople. The esthetic impact was the same, whether the canine was exposed with a closed or an open surgical technique.

Social and psychosocial factors associated with high-risk sexual behaviour among university students in the United Kingdom: a web-survey.

In the UK there are limited data about university students’ risky sexual behaviour. A cross-sectional web-survey was conducted to investigate factors associated with high-risk sex among students at two UK universities. High-risk sex was reported by 25% of 1108. High personal sexually transmitted infection (STI) risk perception and permissive attitudes towards casual sex were associated with high-risk sex for both men (odds ratio [OR]: 12.12; 95% confidence interval [CI]: 4.10–35.81; OR: 2.49; 95%CI: 1.11–5.56, respectively) and women (OR: 22.31; 95% CI: 9.34–53.26; OR: 3.02; 95% CI: 1.82–5.01, respectively). For men, drinking alcohol (OR: 17.67; 95% CI: 1.90–164.23) and for women age and frequent drinking (OR: 2.02; 95% CI: 1.05–3.89; OR: 1.89; 95% CI: 1.08–3.31, respectively) were associated with high-risk sex. However, perceiving an average student as more likely to contract STIs (men, OR: 0.34; 95% CI: 0.16–0.75) or HIV (men, OR: 0.44; 95% CI: 0.20–0.96; women, OR: 0.42; 95% CI: 0.28–0.63) and finding it difficult to discuss sexual matters (women, OR: 0.60; 95% CI: 0.39–0.91) were negatively associated with high-risk sex. Most of the factors found were similar to other populations, but some psychosocial factors showed complex patterns of association that require further investigation.

An assessment of the psychometric performance of the Health Utilities Index 2 and 3 in children following discharge from a U.K. pediatric intensive care unit.

Objective: Our objective was to assess the psychometric performance of the Health Utilities Index 2 and 3 in a pediatric population following admission to a pediatric intensive care unit. Design: As part of a larger study of pediatric intensive care outcomes, children were followed up at 6 and 12 months post admission from pediatric intensive care using the Health Utilities Index 2 and 3. We evaluated and compared the psychometric performance of the Health Utilities Index 2 and 3 in this population by assessing their practicality, reliability, and limited information regarding validity. Setting: Twenty-two pediatric intensive care units in the United Kingdom. Patients: A total of 685 children aged 5 yrs and over. Interventions: The Health Utilities Index 2 and 3, which are both generic preference-based measures of health-related quality of life, were completed by proxy and children over 11 yrs of age were invited to self-complete. Measurement and Main Results: Both Health Utilities Index 2 and 3 demonstrated good practicality, with excellent completion rates (>97%) and a mean time to complete of around 8 mins. Both Health Utilities Index 2 and 3 demonstrated very good inter-rater reliability and evidence of sensitivity to change. At 6 months after admission, mean scores of the Health Utilities Index 2 and 3 were different in some groups of children with different degrees of in-hospital severity of illness, but those differences were not found at 12 months of follow-up. Conclusions: The Health Utilities Index 2 and 3 both perform well in a pediatric intensive care setting whether by self-complete or proxy complete. Evidence of good inter-rater reliability gives confidence that the measures can be reliably used with a proxy completer, such as parent or caregiver. Additional research is important to investigate their construct validity further in this population, ideally using baseline data collected at the time of hospital stay in pediatric intensive care and other measures of health status at the times of follow-up.

Saline in Acute Bronchiolitis RCT and Economic evaluation: hypertonic saline in acute bronchiolitis – randomised controlled trial and systematic review

BACKGROUND Acute bronchiolitis is the most common cause of hospitalisation in infancy. Supportive care and oxygen are the cornerstones of management. A Cochrane review concluded that the use of nebulised 3% hypertonic saline (HS) may significantly reduce the duration of hospitalisation. OBJECTIVE To test the hypothesis that HS reduces the time to when infants were assessed as being fit for discharge, defined as in air with saturations of > 92% for 6 hours, by 25%. DESIGN Parallel-group, pragmatic randomised controlled trial, cost-utility analysis and systematic review. SETTING Ten UK hospitals. PARTICIPANTS Infants with acute bronchiolitis requiring oxygen therapy were allocated within 4 hours of admission. INTERVENTIONS Supportive care with oxygen as required, minimal handling and fluid administration as appropriate to the severity of the disease, 3% nebulised HS every ± 6 hours. MAIN OUTCOME MEASURES The trial primary outcome was time until the infant met objective discharge criteria. Secondary end points included time to discharge and adverse events. The costs analysed related to length of stay (LoS), readmissions, nebulised saline and other NHS resource use. Quality-adjusted life-years (QALYs) were estimated using an existing utility decrement derived for hospitalisation in children, together with the time spent in hospital in the trial. DATA SOURCES We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials and other databases from inception or from 2010 onwards, searched ClinicalTrials.gov and other registries and hand-searched Chest, Paediatrics and Journal of Paediatrics to January 2015. REVIEW METHODS We included randomised/quasi-randomised trials which compared HS versus saline (± adjunct treatment) or no treatment. We used a fixed-effects model to combine mean differences for LoS and assessed statistical heterogeneity using the I (2) statistic. RESULTS The trial randomised 158 infants to HS (n = 141 analysed) and 159 to standard care (n = 149 analysed). There was no difference between the two arms in the time to being declared fit for discharge [median 76.6 vs. 75.9 hours, hazard ratio (HR) 0.95, 95% confidence interval (CI) 0.75 to 1.20] or to actual discharge (median 88.5 vs. 88.7 hours, HR 0.97, 95% CI 0.76 to 1.23). There was no difference in adverse events. One infant developed bradycardia with desaturation associated with HS. Mean hospital costs were £2595 and £2727 for the control and intervention groups, respectively (p = 0.657). Incremental QALYs were 0.0000175 (p = 0.757). An incremental cost-effectiveness ratio of £7.6M per QALY gained was not appreciably altered by sensitivity analyses. The systematic review comprised 15 trials (n = 1922) including our own. HS reduced the mean LoS by -0.36 days (95% CI -0.50 to -0.22 days). High levels of heterogeneity (I (2) = 78%) indicate that the result should be treated cautiously. CONCLUSIONS In this trial, HS had no clinical benefit on LoS or readiness for discharge and was not a cost-effective treatment for acute bronchiolitis. Claims that HS achieves small reductions in LoS must be treated with scepticism. FUTURE WORK Well-powered randomised controlled trials of high-flow oxygen are needed. STUDY REGISTRATION This study is registered as NCT01469845 and CRD42014007569. FUNDING DETAILS This project was funded by the NIHR Health Technology Assessment (HTA) programme and will be published in full in Health Technology Assessment; Vol. 19, No. 66. See the HTA programme website for further project information.

How to spot a statistical problem: advice for a non-statistical reviewer

Statistical analyses presented in general medical journals are becoming increasingly sophisticated. BMC Medicine relies on subject reviewers to indicate when a statistical review is required. We consider this policy and provide guidance on when to recommend a manuscript for statistical evaluation. Indicators for statistical review include insufficient detail in methods or results, some common statistical issues and interpretation not based on the presented evidence. Reviewers are required to ensure that the manuscript is methodologically sound and clearly written. Within that context, they are expected to provide constructive feedback and opinion on the statistical design, analysis, presentation and interpretation. If reviewers lack the appropriate background to positively confirm the appropriateness of any of the manuscript’s statistical aspects, they are encouraged to recommend it for expert statistical review.

Bypassing nearest hospital for more distant neuroscience care in head-injured adults with suspected traumatic brain injury: findings of the head injury transportation straight to neurosurgery (HITS-NS) pilot cluster randomised trial

Objective Reconfiguration of trauma services, with direct transport of patients with traumatic brain injury (TBI) to specialist neuroscience centres (SNCs)—bypassing non-specialist acute hospitals (NSAHs), could improve outcomes. However, delays in stabilisation of airway, breathing and circulation (ABC) may worsen outcomes when compared with selective secondary transfer from nearest NSAH to SNC. We conducted a pilot cluster randomised controlled trial to determine the feasibility and plausibility of bypassing suspected patients with TBI —directly into SNCs—producing a measurable effect. Setting Two English Ambulance Services. Participants 74 clusters (ambulance stations) were randomised within pairs after matching for important characteristics. Clusters enrolled head-injured adults—injured nearest to an NSAH—with internationally accepted TBI risk factors and stable ABC. We excluded participants attended by Helicopter Emergency Medical Services or who were injured more than 1 hour by road from nearest SNC. Interventions Intervention cluster participants were transported directly to an SNC bypassing nearest NSAH; control cluster participants were transported to nearest NSAH with selective secondary transfer to SNC. Outcomes Trial recruitment rate (target n=700 per annum) and percentage with TBI on CT scan (target 80%) were the primary feasibility outcomes. 30-day mortality, 6-month Extended Glasgow Outcome Scale and quality of life were secondary outcomes. Results 56 ambulance station clusters recruited 293 patients in 12 months. The trial arms were similar in terms of age, conscious level and injury severity. Less than 25% of recruited patients had TBI on CT (n=70) with 7% (n=20) requiring neurosurgery. Complete case analysis showed similar 30-day mortality in the two trial arms (control=8.8 (2.7–14.0)% vs intervention=9.4(2.3–14.0)%). Conclusion Bypassing patients with suspected TBI to SNCs gives an overtriage (false positive) ratio of 13:1 for neurosurgical intervention and 4:1 for TBI. A measurable effect from a full trial of early neuroscience care following bypass is therefore unlikely. Trial registration number ISRCTN68087745.