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The Gaussian process is an indispensable tool for spatial data analysts. The onset of the “big data” era, however, has lead to the traditional Gaussian process being computationally infeasible for modern spatial data. As such, various alternatives to the full Gaussian process that are more amenable to handling big spatial data have been proposed. These modern methods often exploit low-rank structures and/or multi-core and multi-threaded computing environments to facilitate computation. This study provides, first, an introductory overview of several methods for analyzing large spatial data. Second, this study describes the results of a predictive competition among the described methods as implemented by different groups with strong expertise in the methodology. Specifically, each research group was provided with two training datasets (one simulated and one observed) along with a set of prediction locations. Each group then wrote their own implementation of their method to produce predictions at the given location and each was subsequently run on a common computing environment. The methods were then compared in terms of various predictive diagnostics.

Background Interrupted time series analysis is increasingly used to evaluate the impact of large-scale health interventions. While segmented regression is a common approach, it is not always adequate, especially in the presence of seasonality and autocorrelation. An Autoregressive Integrated Moving Average (ARIMA) model is an alternative method that can accommodate these issues. Methods We describe the underlying theory behind ARIMA models and how they can be used to evaluate population-level interventions, such as the introduction of health policies. We discuss how to select the shape of the impact, the model selection process, transfer functions, checking model fit, and interpretation of findings. We also provide R and SAS code to replicate our results. Results We illustrate ARIMA modelling using the example of a policy intervention to reduce inappropriate prescribing. In January 2014, the Australian government eliminated prescription refills for the 25 mg tablet strength of quetiapine, an antipsychotic, to deter its prescribing for non-approved indications. We examine the impact of this policy intervention on dispensing of quetiapine using dispensing claims data. Conclusions ARIMA modelling is a useful tool to evaluate the impact of large-scale interventions when other approaches are not suitable, as it can account for underlying trends, autocorrelation and seasonality and allows for flexible modelling of different types of impacts.

Background Single group data present unique challenges for synthesises of evidence. Proportional meta-analysis is becoming an increasingly common technique employed for the synthesis of single group data. Proportional meta-analysis shares many similarities with the conduct and reporting of comparative, or pairwise, meta-analysis. While robust and comprehensive methods exist detailing how researchers can conduct a meta-analysis that compares two (or more) groups against a common intervention, there is a scarcity of methodological guidance available to assist synthesisers of evidence in the conduct, interpretation, and importance of proportional meta-analysis in systematic reviews. Main body This paper presents an overview targeted to synthesisers of evidence and systematic review authors that details the methods, importance, and interpretation of a proportional meta-analysis. We provide worked examples of how proportional meta-analyses have been conducted in research syntheses previously and consider the methods, statistical considerations, and presentation of this technique. Conclusion This overview is designed to serve as practical guidance for synthesisers of evidence in the conduct of proportional meta-analyses.

Background Medical practitioners use survival models to explore and understand the relationships between patients’ covariates (e.g. clinical and genetic features) and the effectiveness of various treatment options. Standard survival models like the linear Cox proportional hazards model require extensive feature engineering or prior medical knowledge to model treatment interaction at an individual level. While nonlinear survival methods, such as neural networks and survival forests, can inherently model these high-level interaction terms, they have yet to be shown as effective treatment recommender systems. Methods We introduce DeepSurv, a Cox proportional hazards deep neural network and state-of-the-art survival method for modeling interactions between a patient’s covariates and treatment effectiveness in order to provide personalized treatment recommendations. Results We perform a number of experiments training DeepSurv on simulated and real survival data. We demonstrate that DeepSurv performs as well as or better than other state-of-the-art survival models and validate that DeepSurv successfully models increasingly complex relationships between a patient’s covariates and their risk of failure. We then show how DeepSurv models the relationship between a patient’s features and effectiveness of different treatment options to show how DeepSurv can be used to provide individual treatment recommendations. Finally, we train DeepSurv on real clinical studies to demonstrate how it’s personalized treatment recommendations would increase the survival time of a set of patients. Conclusions The predictive and modeling capabilities of DeepSurv will enable medical researchers to use deep neural networks as a tool in their exploration, understanding, and prediction of the effects of a patient’s characteristics on their risk of failure.

Background Stringent requirements exist regarding the transparency of the study selection process and the reliability of results. A 2-step selection process is generally recommended; this is conducted by 2 reviewers independently of each other (conventional double-screening). However, the approach is resource intensive, which can be a problem, as systematic reviews generally need to be completed within a defined period with a limited budget. The aim of the following methodological systematic review was to analyse the evidence available on whether single screening is equivalent to double screening in the screening process conducted in systematic reviews. Methods We searched Medline, PubMed and the Cochrane Methodology Register (last search 10/2018). We also used supplementary search techniques and sources (“similar articles” function in PubMed, conference abstracts and reference lists). We included all evaluations comparing single with double screening. Data were summarized in a structured, narrative way. Results The 4 evaluations included investigated a total of 23 single screenings (12 sets for screening involving 9 reviewers). The median proportion of missed studies was 5% (range 0 to 58%). The median proportion of missed studies was 3% for the 6 experienced reviewers (range: 0 to 21%) and 13% for the 3 reviewers with less experience (range: 0 to 58%). The impact of missing studies on the findings of meta-analyses had been reported in 2 evaluations for 7 single screenings including a total of 18,148 references. In 3 of these 7 single screenings – all conducted by the same reviewer (with less experience) – the findings would have changed substantially. The remaining 4 of these 7 screenings were conducted by experienced reviewers and the missing studies had no impact or a negligible on the findings of the meta-analyses. Conclusions Single screening of the titles and abstracts of studies retrieved in bibliographic searches is not equivalent to double screening, as substantially more studies are missed. However, in our opinion such an approach could still represent an appropriate methodological shortcut in rapid reviews, as long as it is conducted by an experienced reviewer. Further research on single screening is required, for instance, regarding factors influencing the number of studies missed.

In risk evaluation, the effect of mixtures of environmental chemicals on a common adverse outcome is of interest. However, due to the high dimensionality and inherent correlations among chemicals that occur together, the traditional methods (e.g. ordinary or logistic regression) suffer from collinearity and variance inflation, and shrinkage methods have limitations in selecting among correlated components. We propose a weighted quantile sum (WQS) approach to estimating a body burden index, which identifies \"bad actors\" in a set of highly correlated environmental chemicals. We evaluate and characterize the accuracy of WQS regression in variable selection through extensive simulation studies through sensitivity and specificity (i.e., ability of the WQS method to select the bad actors correctly and not incorrect ones). We demonstrate the improvement in accuracy this method provides over traditional ordinary regression and shrinkage methods (lasso, adaptive lasso, and elastic net). Results from simulations demonstrate that WQS regression is accurate under some environmentally relevant conditions, but its accuracy decreases for a fixed correlation pattern as the association with a response variable diminishes. Nonzero weights (i.e., weights exceeding a selection threshold parameter) may be used to identify bad actors; however, components within a cluster of highly correlated active components tend to have lower weights, with the sum of their weights representative of the set. Supplementary materials accompanying this paper appear on-line.

Background In systematic reviews and meta-analysis, researchers often pool the results of the sample mean and standard deviation from a set of similar clinical trials. A number of the trials, however, reported the study using the median, the minimum and maximum values, and/or the first and third quartiles. Hence, in order to combine results, one may have to estimate the sample mean and standard deviation for such trials. Methods In this paper, we propose to improve the existing literature in several directions. First, we show that the sample standard deviation estimation in Hozo et al.’s method (BMC Med Res Methodol 5:13, 2005) has some serious limitations and is always less satisfactory in practice. Inspired by this, we propose a new estimation method by incorporating the sample size. Second, we systematically study the sample mean and standard deviation estimation problem under several other interesting settings where the interquartile range is also available for the trials. Results We demonstrate the performance of the proposed methods through simulation studies for the three frequently encountered scenarios, respectively. For the first two scenarios, our method greatly improves existing methods and provides a nearly unbiased estimate of the true sample standard deviation for normal data and a slightly biased estimate for skewed data. For the third scenario, our method still performs very well for both normal data and skewed data. Furthermore, we compare the estimators of the sample mean and standard deviation under all three scenarios and present some suggestions on which scenario is preferred in real-world applications. Conclusions In this paper, we discuss different approximation methods in the estimation of the sample mean and standard deviation and propose some new estimation methods to improve the existing literature. We conclude our work with a summary table (an Excel spread sheet including all formulas) that serves as a comprehensive guidance for performing meta-analysis in different situations.

Background Missing data may seriously compromise inferences from randomised clinical trials, especially if missing data are not handled appropriately. The potential bias due to missing data depends on the mechanism causing the data to be missing, and the analytical methods applied to amend the missingness. Therefore, the analysis of trial data with missing values requires careful planning and attention. Methods The authors had several meetings and discussions considering optimal ways of handling missing data to minimise the bias potential. We also searched PubMed (key words: missing data; randomi*; statistical analysis) and reference lists of known studies for papers (theoretical papers; empirical studies; simulation studies; etc.) on how to deal with missing data when analysing randomised clinical trials. Results Handling missing data is an important, yet difficult and complex task when analysing results of randomised clinical trials. We consider how to optimise the handling of missing data during the planning stage of a randomised clinical trial and recommend analytical approaches which may prevent bias caused by unavoidable missing data. We consider the strengths and limitations of using of best-worst and worst-best sensitivity analyses, multiple imputation, and full information maximum likelihood. We also present practical flowcharts on how to deal with missing data and an overview of the steps that always need to be considered during the analysis stage of a trial. Conclusions We present a practical guide and flowcharts describing when and how multiple imputation should be used to handle missing data in randomised clinical.

Background Choosing a suitable sample size in qualitative research is an area of conceptual debate and practical uncertainty. That sample size principles, guidelines and tools have been developed to enable researchers to set, and justify the acceptability of, their sample size is an indication that the issue constitutes an important marker of the quality of qualitative research. Nevertheless, research shows that sample size sufficiency reporting is often poor, if not absent, across a range of disciplinary fields. Methods A systematic analysis of single-interview-per-participant designs within three health-related journals from the disciplines of psychology, sociology and medicine, over a 15-year period, was conducted to examine whether and how sample sizes were justified and how sample size was characterised and discussed by authors. Data pertinent to sample size were extracted and analysed using qualitative and quantitative analytic techniques. Results Our findings demonstrate that provision of sample size justifications in qualitative health research is limited; is not contingent on the number of interviews; and relates to the journal of publication. Defence of sample size was most frequently supported across all three journals with reference to the principle of saturation and to pragmatic considerations. Qualitative sample sizes were predominantly – and often without justification – characterised as insufficient (i.e., ‘small’) and discussed in the context of study limitations. Sample size insufficiency was seen to threaten the validity and generalizability of studies’ results, with the latter being frequently conceived in nomothetic terms. Conclusions We recommend, firstly, that qualitative health researchers be more transparent about evaluations of their sample size sufficiency, situating these within broader and more encompassing assessments of data adequacy . Secondly, we invite researchers critically to consider how saturation parameters found in prior methodological studies and sample size community norms might best inform, and apply to, their own project and encourage that data adequacy is best appraised with reference to features that are intrinsic to the study at hand. Finally, those reviewing papers have a vital role in supporting and encouraging transparent study-specific reporting.

This paper aims to highlight the potential applications and limits of a large language model (LLM) in healthcare. ChatGPT is a recently developed LLM that was trained on a massive dataset of text for dialogue with users. Although AI-based language models like ChatGPT have demonstrated impressive capabilities, it is uncertain how well they will perform in real-world scenarios, particularly in fields such as medicine where high-level and complex thinking is necessary. Furthermore, while the use of ChatGPT in writing scientific articles and other scientific outputs may have potential benefits, important ethical concerns must also be addressed. Consequently, we investigated the feasibility of ChatGPT in clinical and research scenarios: (1) support of the clinical practice, (2) scientific production, (3) misuse in medicine and research, and (4) reasoning about public health topics. Results indicated that it is important to recognize and promote education on the appropriate use and potential pitfalls of AI-based LLMs in medicine.