Liver resection surgery compared with thermal ablation in high surgical risk patients with colorectal liver metastases: the LAVA international RCT.

BACKGROUND: Although surgical resection has been considered the only curative option for colorectal liver metastases, thermal ablation has recently been suggested as an alternative curative treatment. There have been no adequately powered trials comparing surgery with thermal ablation. OBJECTIVES: Main objective - to compare the clinical effectiveness and cost-effectiveness of thermal ablation versus liver resection surgery in high surgical risk patients who would be eligible for liver resection. Pilot study objectives - to assess the feasibility of recruitment (through qualitative study), to assess the quality of ablations and liver resection surgery to determine acceptable standards for the main trial and to centrally review the reporting of computed tomography scan findings relating to ablation and outcomes and recurrence rate in both arms. DESIGN: A prospective, international (UK and the Netherlands), multicentre, open, pragmatic, parallel-group, randomised controlled non-inferiority trial with a 1-year internal pilot study. SETTING: Tertiary liver, pancreatic and gallbladder (hepatopancreatobiliary) centres in the UK and the Netherlands. PARTICIPANTS: Adults with a specialist multidisciplinary team diagnosis of colorectal liver metastases who are at high surgical risk because of their age, comorbidities or tumour burden and who would be suitable for liver resection or thermal ablation. INTERVENTIONS: Thermal ablation conducted as per local policy (but centres were encouraged to recruit within Cardiovascular and Interventional Radiological Society of Europe guidelines) versus surgical liver resection performed as per centre protocol. MAIN OUTCOME MEASURES: Pilot study - patients' and clinicians' acceptability of the trial to assist in optimisation of recruitment. Primary outcome - disease-free survival at 2 years post randomisation. Secondary outcomes - overall survival, timing and site of recurrence, additional therapy after treatment failure, quality of life, complications, length of hospital stay, costs, trial acceptability, and disease-free survival measured from end of intervention. It was planned that 5-year survival data would be documented through record linkage. Randomisation was performed by minimisation incorporating a random element, and this was a non-blinded study. RESULTS: In the pilot study over 1 year, a total of 366 patients with colorectal liver metastases were screened and 59 were considered eligible. Only nine participants were randomised. The trial was stopped early and none of the planned statistical analyses was performed. The key issues inhibiting recruitment included fewer than anticipated patients eligible for both treatments, misconceptions about the eligibility criteria for the trial, surgeons' preference for one of the treatments ('lack of clinical equipoise' among some of the surgeons in the centre) with unconscious bias towards surgery, patients' preference for one of the treatments, and lack of dedicated research nurses for the trial. CONCLUSIONS: Recruitment feasibility was not demonstrated during the pilot stage of the trial; therefore, the trial closed early. In future, comparisons involving two very different treatments may benefit from an initial feasibility study or a longer period of internal pilot study to resolve these difficulties. Sufficient time should be allowed to set up arrangements through National Institute for Health Research (NIHR) Research Networks. TRIAL REGISTRATION: Current Controlled Trials ISRCTN52040363. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 21. See the NIHR Journals Library website for further project information

Remission outcomes in severe eosinophilic asthma with mepolizumab therapy: Analysis of the REDES study

IntroductionClinical remission as a multicomponent treatment goal in severe asthma is being explored in clinical practice. This post hoc analysis used data from the REDES study to assess the proportion of patients with severe eosinophilic asthma achieving our multicomponent definitions of clinical remission after 1 year of mepolizumab treatment.MethodsThe real-world, retrospective observational REDES study enrolled patients with severe eosinophilic asthma who were newly prescribed mepolizumab and with ≥12 months of medical records pre-enrolment. Multicomponent clinical remission was defined as: oral corticosteroid (OCS)-free; exacerbation-free; asthma control test (ACT) score ≥20; and with or without post-bronchodilator forced expiratory volume in 1 second ≥80%. Baseline characteristics were also assessed in those who did/did not achieve clinical remission.Results37% and 30% of patients with severe eosinophilic asthma met our proposed three- and four-component on-treatment clinical remission definitions; an increase from 2% and 3% at baseline. Most frequently achieved individual components of clinical remission were: OCS-free; ACT score ≥20. For patients fulfilling the multicomponent clinical remission definitions, at baseline we observed higher blood eosinophil counts, better ACT scores and lung function, lower maintenance OCS use, and a slightly lower rate of prior exacerbations versus those who did not.DiscussionClinical remission is a realistic target in clinical practice for a subset of patients with severe eosinophilic asthma receiving mepolizumab. Further studies are required to elucidate whether features linked to the underlying endotype can help predict treatment outcomes, increase rates of clinical remission, and potentially modify disease progression

Heterogeneity in transmission parameters of hookworm infection within the baseline data from the TUMIKIA study in Kenya.

BACKGROUND: As many countries with endemic soil-transmitted helminth (STH) burdens achieve high coverage levels of mass drug administration (MDA) to treat school-aged and pre-school-aged children, understanding the detailed effects of MDA on the epidemiology of STH infections is desirable in formulating future policies for morbidity and/or transmission control. Prevalence and mean intensity of infection are characterized by heterogeneity across a region, leading to uncertainty in the impact of MDA strategies. In this paper, we analyze this heterogeneity in terms of factors that govern the transmission dynamics of the parasite in the host population. RESULTS: Using data from the TUMIKIA study in Kenya (cluster STH prevalence range at baseline: 0-63%), we estimated these parameters and their variability across 120 population clusters in the study region, using a simple parasite transmission model and Gibbs-sampling Monte Carlo Markov chain techniques. We observed great heterogeneity in R0 values, with estimates ranging from 1.23 to 3.27, while k-values (which vary inversely with the degree of parasite aggregation within the human host population) range from 0.007 to 0.29 in a positive association with increasing prevalence. The main finding of this study is the increasing trend for greater parasite aggregation as prevalence declines to low levels, reflected in the low values of the negative binomial parameter k in clusters with low hookworm prevalence. Localized climatic and socioeconomic factors are investigated as potential drivers of these observed epidemiological patterns. CONCLUSIONS: Our results show that lower prevalence is associated with higher degrees of aggregation and hence prevalence alone is not a good indicator of transmission intensity. As a consequence, approaches to MDA and monitoring and evaluation of community infection status may need to be adapted as transmission elimination is aimed for by targeted treatment approaches

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Geostatistical modeling of malaria endemicity using serological indicators of exposure collected through school surveys.

Ethiopia has a diverse ecology and geography resulting in spatial and temporal variation in malaria transmission. Evidence-based strategies are thus needed to monitor transmission intensity and target interventions. A purposive selection of dried blood spots collected during cross-sectional school-based surveys in Oromia Regional State, Ethiopia, were tested for presence of antibodies against Plasmodium falciparum and P. vivax antigens. Spatially explicit binomial models of seroprevalence were created for each species using a Bayesian framework, and used to predict seroprevalence at 5 km resolution across Oromia. School seroprevalence showed a wider prevalence range than microscopy for both P. falciparum (0-50% versus 0-12.7%) and P. vivax (0-53.7% versus 0-4.5%), respectively. The P. falciparum model incorporated environmental predictors and spatial random effects, while P. vivax seroprevalence first-order trends were not adequately explained by environmental variables, and a spatial smoothing model was developed. This is the first demonstration of serological indicators being used to detect large-scale heterogeneity in malaria transmission using samples from cross-sectional school-based surveys. The findings support the incorporation of serological indicators into periodic large-scale surveillance such as Malaria Indicator Surveys, and with particular utility for low transmission and elimination settings

Liver resection surgery compared with thermal ablation in high surgical risk patients with colorectal liver metastases: the LAVA international RCT

Contains fulltext : 218983.pdf (publisher's version ) (Open Access

DataSheet_1_Remission outcomes in severe eosinophilic asthma with mepolizumab therapy: Analysis of the REDES study.docx

IntroductionClinical remission as a multicomponent treatment goal in severe asthma is being explored in clinical practice. This post hoc analysis used data from the REDES study to assess the proportion of patients with severe eosinophilic asthma achieving our multicomponent definitions of clinical remission after 1 year of mepolizumab treatment.MethodsThe real-world, retrospective observational REDES study enrolled patients with severe eosinophilic asthma who were newly prescribed mepolizumab and with ≥12 months of medical records pre-enrolment. Multicomponent clinical remission was defined as: oral corticosteroid (OCS)-free; exacerbation-free; asthma control test (ACT) score ≥20; and with or without post-bronchodilator forced expiratory volume in 1 second ≥80%. Baseline characteristics were also assessed in those who did/did not achieve clinical remission.Results37% and 30% of patients with severe eosinophilic asthma met our proposed three- and four-component on-treatment clinical remission definitions; an increase from 2% and 3% at baseline. Most frequently achieved individual components of clinical remission were: OCS-free; ACT score ≥20. For patients fulfilling the multicomponent clinical remission definitions, at baseline we observed higher blood eosinophil counts, better ACT scores and lung function, lower maintenance OCS use, and a slightly lower rate of prior exacerbations versus those who did not.DiscussionClinical remission is a realistic target in clinical practice for a subset of patients with severe eosinophilic asthma receiving mepolizumab. Further studies are required to elucidate whether features linked to the underlying endotype can help predict treatment outcomes, increase rates of clinical remission, and potentially modify disease progression.</p

Liver resection surgery versus thermal ablation for colorectal LiVer MetAstases (LAVA):study protocol for a randomised controlled trial

Background: Although surgical resection has been considered the only curative option for colorectal liver metastases (CLM), thermal ablation has recently been suggested as an alternative curative treatment. A prospective randomised trial is required to define the efficacy of resection vs ablation for the treatment of colorectal liver metastases. Methods: Design and setting: This is a multicentre, open, randomised controlled non-inferiority trial design with internal pilot and will be performed in tertiary liver centres in UK and The Netherlands. Participants: Eligible patients will be those with colorectal liver metastases at high surgical risk because of their age, co-morbidities or tumour burden and who would be suitable for liver resection or thermal ablation. Intervention: Thermal ablation as per local policy. Control: Surgical liver resection performed as per centre protocol. Co-interventions: Further chemotherapy will be offered to patients as per current practice. Outcomes: Pilot study: Same as main study and in addition patients and clinicians’ acceptability of the trial to assist in optimisation of recruitment. Primary outcome: Disease-free survival (DFS) at two years post randomisation. Secondary outcomes: Overall survival, timing and site of recurrence, additional therapy after treatment failure, quality of life, complications, length of hospital stay, costs, trial acceptability, DFS measured from end of intervention. Follow-up: 24 months from randomisation; five-year follow-up for overall survival. Sample size: 330 patients to demonstrate non-inferiority of thermal ablation. Discussion: This trial will determine the effectiveness and cost-effectiveness of thermal ablation vs surgical resection for high-risk people with colorectal liver metastases, and guide the optimal treatment for these patients

Image_1_Remission outcomes in severe eosinophilic asthma with mepolizumab therapy: Analysis of the REDES study.tif

IntroductionClinical remission as a multicomponent treatment goal in severe asthma is being explored in clinical practice. This post hoc analysis used data from the REDES study to assess the proportion of patients with severe eosinophilic asthma achieving our multicomponent definitions of clinical remission after 1 year of mepolizumab treatment.MethodsThe real-world, retrospective observational REDES study enrolled patients with severe eosinophilic asthma who were newly prescribed mepolizumab and with ≥12 months of medical records pre-enrolment. Multicomponent clinical remission was defined as: oral corticosteroid (OCS)-free; exacerbation-free; asthma control test (ACT) score ≥20; and with or without post-bronchodilator forced expiratory volume in 1 second ≥80%. Baseline characteristics were also assessed in those who did/did not achieve clinical remission.Results37% and 30% of patients with severe eosinophilic asthma met our proposed three- and four-component on-treatment clinical remission definitions; an increase from 2% and 3% at baseline. Most frequently achieved individual components of clinical remission were: OCS-free; ACT score ≥20. For patients fulfilling the multicomponent clinical remission definitions, at baseline we observed higher blood eosinophil counts, better ACT scores and lung function, lower maintenance OCS use, and a slightly lower rate of prior exacerbations versus those who did not.DiscussionClinical remission is a realistic target in clinical practice for a subset of patients with severe eosinophilic asthma receiving mepolizumab. Further studies are required to elucidate whether features linked to the underlying endotype can help predict treatment outcomes, increase rates of clinical remission, and potentially modify disease progression.</p