Congenital diaphragmatic hernia-influence of fetoscopic tracheal occlusion on outcomes and predictors of survival.

UNLABELLED: The morbidity of infants with congenital diaphragmatic hernia (CDH) who had undergone foetal endoscopic tracheal occlusion (FETO) to those who had not was compared and predictors of survival regardless of antenatal intervention were identified. FETO was undertaken on the basis of the lung to head ratio or the position of the liver. A retrospective review of the records of 78 CDH infants was undertaken to determine the lung-head ratio (LHR) at referral and prior to birth, maximum oxygen saturation in the labour suite and neonatal outcomes. The 43 FETO infants were born earlier (mean 34 versus 38 weeks) (p < 0.001). They had a lower mean LHR at referral (0.65 versus 1.24) (p < 0.001) but not prior to birth and did not have a higher mortality than the 35 non-FETO infants. The FETO infants required significantly longer durations of ventilation (median: 15 versus 6 days) and supplementary oxygen (28 versus 8 days) and hospital stay (29 versus 16 days). Overall, the best predictor of survival was the OI in the first 24 h. CONCLUSION: The FETO group had increased morbidity, but not mortality. The lowest oxygenation index in the first 24 h was the best predictor of survival regardless of antenatal intervention. WHAT IS KNOWN: • Randomised controlled trials have demonstrated that foetal endotracheal occlusion (FETO) in high risk infants with congenital diaphragmatic hernia is associated with a higher survival rate. • Mortality is greater in foetuses who underwent FETO and delivered prior to 35 weeks of gestation. What is New: • Infants who had undergone FETO compared to those who had not had significantly longer durations of mechanical ventilation, supplementary oxygen and hospital stay. • Regardless of antenatal intervention, the lowest oxygenation index in the first 24 h was the best predictor of survival.

Dichotomisation using a distributional approach when the outcome is skewed.

BACKGROUND: Dichotomisation of continuous outcomes has been rightly criticised by statisticians because of the loss of information incurred. However to communicate a comparison of risks, dichotomised outcomes may be necessary. Peacock et al. developed a distributional approach to the dichotomisation of normally distributed outcomes allowing the presentation of a comparison of proportions with a measure of precision which reflects the comparison of means. Many common health outcomes are skewed so that the distributional method for the dichotomisation of continuous outcomes may not apply. METHODS: We present a methodology to obtain dichotomised outcomes for skewed variables illustrated with data from several observational studies. We also report the results of a simulation study which tests the robustness of the method to deviation from normality and assess the validity of the newly developed method. RESULTS: The review showed that the pattern of dichotomisation was varying between outcomes. Birthweight, Blood pressure and BMI can either be transformed to normal so that normal distributional estimates for a comparison of proportions can be obtained or better, the skew-normal method can be used. For gestational age, no satisfactory transformation is available and only the skew-normal method is reliable. The normal distributional method is reliable also when there are small deviations from normality. CONCLUSIONS: The distributional method with its applicability for common skewed data allows researchers to provide both continuous and dichotomised estimates without losing information or precision. This will have the effect of providing a practical understanding of the difference in means in terms of proportions.

Systematic review of methodology used in clinical studies evaluating the benefits of proton beam therapy.

BACKGROUND: Proton beam therapy (PBT) delivers high-energy radiation to target tumours while sparing surrounding normal tissues. The dosimetric advantages of PBT over traditional photon radiotherapy may be clear but the translation of this benefit into clinically meaningful reductions in toxicities and improved quality-of-life (QoL) needs to be determined. Randomised controlled trials (RCTs) are considered the gold standard for generating the highest-level evidence in medicine. The objectives of this systematic review were to provide an overview of published clinical studies evaluating the benefits of PBT, and to examine the methodology used in clinical trials with respect to study design and outcomes. METHODS: PubMed, EMBASE and Cochrane databases were systematically searched for published clinical studies where PBT was a cancer treatment intervention. All randomised and non-randomised studies, prospective or retrospective, were eligible for inclusion. RESULTS: In total, 219 studies were included. Prospective studies comprised 89/219 (41%), and of these, the number of randomised phase II and III trials were 5/89 (6%) and 3/89 (3%) respectively. Of all the phase II and III trials, 18/24 (75%) were conducted at a single PBT centre. Over one-third of authors recommended an increase in length of follow up. Research design and/or findings were poorly reported in 74/89 (83%) of prospective studies. Patient reported outcomes were assessed in only 19/89 (21%) of prospective studies. CONCLUSIONS: Prospective randomised evidence for PBT is limited. The set-up of national PBT services in several countries provides an opportunity to guide the optimal design of prospective studies, including RCTs, to evaluate the benefits of PBT across various disease sites. Collaboration between PBT centres, both nationally and internationally, would increase potential for the generation of practice changing evidence. There is a need to facilitate and guide the collection and analysis of meaningful outcome data, including late toxicities and patient reported QoL.

Magnetic resonance imaging sequence evaluation of an MR Linac system; early clinical experience.

OBJECTIVES: To systematically identify the preferred magnetic resonance imaging (MRI) sequences following volunteer imaging on a 1.5 Tesla (T) MR-Linear Accelerator (MR Linac) for future protocol development. METHODS: Non-patient volunteers were recruited to a Research and Ethics committee approved prospective MR-only imaging study on a 1.5T MR Linac system. Volunteers attended 1-3 imaging sessions that included a combination of mDixon, T1w, T2w sequences using 2-dimensional (2D) and 3-dimensional (3D) acquisitions. Each sequence was acquired over 2-7 minutes and reviewed by a panel of 3 observers to evaluate image quality using a visual grading analysis based on a 4-point Likert scale. Sequences were acquired and modified iteratively until deemed fit for purpose (online image matching or re-planning) and all observers agreed they were suitable in 3 volunteers. RESULTS: 26 volunteers underwent 31 imaging sessions of six general anatomical regions. Images were acquired in one or two of six general anatomical regions: male pelvis (n = 9), female pelvis (n = 4), chestwall/breast (n = 5), lung/oesophagus (n = 5), abdomen (n = 3) and head and neck (n = 5). Images were acquired using a pre-defined exam-card that on average, included six sequences (range 2-10), with a maximum scan time of approximately one hour. The majority of observers preferred T2-weighted sequences. The thorax teams were the only groups to prefer T1-weighted imaging. CONCLUSIONS: An iterative process identified sequence agreement in all anatomical regions. These sequences will now be evaluated in patient volunteers. ADVANCES IN KNOWLEDGE: This manuscript is the first publication sharing the results of the first systematic selection of MRI sequences for use in on-board MRI-guided radiotherapy by end-users (therapeutic radiographers and clinical oncologists) in healthy volunteers.

Multicentre prospective survey of SeHCAT provision and practice in the UK.

OBJECTIVE: A clinical diagnosis of bile acid malabsorption (BAM) can be confirmed using SeHCAT (tauroselcholic ((75)selenium) acid), a radiolabelled synthetic bile acid. However, while BAM can be the cause of chronic diarrhoea, it is often overlooked as a potential diagnosis. Therefore, we investigated the use of SeHCAT for diagnosis of BAM in UK hospitals. DESIGN: A multicentre survey was conducted capturing centre and patient-level information detailing patient care-pathways, clinical history, SeHCAT results, treatment with bile acid sequestrants (BAS), and follow-up in clinics. Eligible data from 38 centres and 1036 patients were entered into a validated management system. RESULTS: SeHCAT protocol varied between centres, with no standardised patient positioning, and differing referral systems. Surveyed patients had a mean age of 50 years and predominantly women (65%). The mean SeHCAT retention score for all patients was 19% (95% CI 17.8% to 20.3%). However, this differed with suspected BAM type: type 1: 9% (95% CI 6.3% to 11.4%), type 2: 21% (95% CI 19.2% to 23.0%) and type 3: 22% (95% CI 19.6% to 24.2%). Centre-defined 'abnormal' and 'borderline' results represented over 50% of the survey population. BAS treatment was prescribed to only 73% of patients with abnormal results. CONCLUSIONS: The study identified a lack of consistent cut-off/threshold values, with differing centre criteria for defining an 'abnormal' SeHCAT result. BAS prescription was not related in a simple way to the SeHCAT result, nor to the centre-defined result, highlighting a lack of clear patient care-pathways. There is a clear need for a future diagnostic accuracy study and a better understanding of optimal management pathways.

The geko™ electro-stimulation device for venous thromboembolism prophylaxis: a NICE medical technology guidance.

The geko™ device is a single-use, battery-powered, neuromuscular electrostimulation device that aims to reduce the risk of venous thromboembolism (VTE). The National Institute for Health and Care Excellence (NICE) selected the geko™ device for evaluation, and invited the manufacturer, Firstkind Ltd, to submit clinical and economic evidence. King's Technology Evaluation Centre, an External Assessment Centre (EAC) commissioned by the NICE, independently assessed the evidence submitted. The sponsor submitted evidence related to the geko™ device and, in addition, included studies of other related devices as further clinical evidence to support a link between increased blood flow and VTE prophylaxis. The EAC assessed this evidence, conducted its own systematic review and concluded that there is currently limited direct evidence that geko™ prevents VTE. The sponsor's cost model is based on the assumption that patients with an underlying VTE risk and subsequently treated with geko™ will experience a reduction in their baseline risk. The EAC assessed this cost model but questioned the validity of some model assumptions. Using the EACs revised cost model, the cost savings for geko™ prophylaxis against a 'no prophylaxis' strategy were estimated as £197 per patient. Following a second public consultation, taking into account a change in the original draft recommendations, the NICE medical technologies guidance MTG19 was issued in June 2014. This recommended the adoption of the geko™ for use in people with a high risk of VTE and when other mechanical/pharmacological methods of prophylaxis are impractical or contraindicated in selected patients within the National Health Service in England.

Dichotomisation of a continuous outcome and effect on meta-analyses: illustration of the distributional approach using the outcome birthweight.

BACKGROUND: Power and precision are greater in meta-analyses than individual study analyses. However, dichotomisation of continuous outcomes in certain studies poses a problem as estimates from primary studies can only be pooled if they have a common outcome. Meta-analyses may include pooled summaries of either or both the continuous and dichotomous forms, and potentially have a different combination of studies for each depending on whether the outcome was dichotomised in the primary studies or not. This dual-outcome issue can lead to loss of power and/or selection bias. In this study we aimed to illustrate how dichotomisation of a continuous outcome in primary studies may result in biased estimates of pooled risk and odds ratios in meta-analysis using secondary analyses of published meta-analyses with the outcome, birthweight, which is commonly analysed both as continuous, and dichotomous (low birthweight: birthweight < 2,500 g). METHODS: Meta-analyses published in January 2010 - December 2011 were obtained using searches in PubMed, Embase, Web of Science, and Cochrane Database of Systematic Reviews with the outcome birthweight. We used a distributional method to estimate the pooled odds/risk ratio of low birthweight and its standard error as a function of the data reported in the primary studies of the included meta-analyses where accessible. RESULTS: Seventy-six meta-analyses were identified. Thirty-seven percent (28/76) of the meta-analyses reported only the dichotomous form of the outcome while 26% (20/76) reported only the continuous form. In one meta-analysis (1/76), birthweight was analysed as continuous for one intervention and as binary for another and 36% (27/76) presented both dichotomous and continuous birthweight summaries. In meta-analyses with a continuous outcome, primary studies data were accessible in 39/48 and secondary analyses using the distributional approach provided consistent inferences for both the continuous and distributional estimates in 38/39. CONCLUSION: The distributional method applied in primary studies allows both a continuous and dichotomous outcome to be estimated providing consistent inferences. The use of this method in primary studies may restrict selective outcome bias in meta-analyses.

E-vita open plus for treating complex aneurysms and dissections of the thoracic aorta: a NICE medical technology guidance.

The E-vita open plus is a one-stage endoluminal stent graft system used for treating complex aneurysms and dissections of the thoracic aorta. The National Institute for Health and Care Excellence (NICE), as a part of its Medical Technologies Evaluation Programme (MTEP), selected this device for evaluation and invited the manufacturer, JOTEC GmbH, to submit clinical and economic evidence. King's Technology Evaluation Centre (KiTEC), an External Assessment Centre (EAC) commissioned by the NICE, independently critiqued the manufacturer's submissions. The EAC considered that the manufacturer had included most of the relevant evidence for the E-vita open plus, based on international E-vita open registry data for 274 patients, but had provided only limited evidence for the comparators. The EAC therefore conducted a systematic review and meta-analysis of all comparators to supplement the information, and found ten additional studies providing outcome data for the three two-stage comparators. The EAC noted that the cost model submitted by the manufacturer did not include key complications during the procedures. The EAC developed a new economic model incorporating data on complications along with their long-term costs. The revised model indicated that the E-vita open plus might not provide cost savings when compared with some of the comparators in the short-term (1 year), but would have high cost savings in the long-term, from the second year onwards. The NICE Medical Technologies Guidance MTG 16, issued in December 2013, recommended the adoption of the E-vita open plus in selected patients within the National Health Service in England.