Simpson's Paradox and the implications for medical trials.

This paper describes Simpson's paradox, and explains its serious implications for randomised control trials. In particular, we show that for any number of variables we can simulate the result of a controlled trial which uniformly points to one conclusion (such as 'drug is effective') for every possible combination of the variable states, but when a previously unobserved confounding variable is included every possible combination of the variables state points to the opposite conclusion ('drug is not effective'). In other words no matter how many variables are considered, and no matter how 'conclusive' the result, one cannot conclude the result is truly 'valid' since there is theoretically an unobserved confounding variable that could completely reverse the result

Value of information analysis for interventional and counterfactual Bayesian networks in forensic medical sciences

Objectives: Inspired by real-world examples from the forensic medical sciences domain, we seek to determine whether a decision about an interventional action could be subject to amendments on the basis of some incomplete information within the model, and whether it would be worthwhile for the decision maker to seek further information prior to suggesting a decision

Risk assessment and risk management of violent reoffending among prisoners

“The final publication is available at Springer via http://dx.doi.org/10.1016/j.eswa.2015.05.025”

Sequential infection can decrease virulence in a fish–bacterium–fluke interaction: Implications for aquaculture disease management

Hosts are typically infected with multiple strains or genotypes of one or several parasite species. These infections can take place simultaneously, but also at different times, i.e. sequentially, when one of the parasites establishes first. Sequential parasite dynamics are common in nature, but also in intensive farming units such as aquaculture. However, knowledge of effects of previous exposures on virulence of current infections in intensive farming is very limited. This is critical as consecutive epidemics and infection history of a host could underlie failures in management practices and medical intervention of diseases. Here, we explored effects of timing of multiple infections on virulence in two common aquaculture parasites, the bacterium Flavobacterium columnare and the fluke Diplostomum pseudospathaceum. We exposed fish hosts first to flukes and then to bacteria in two separate experiments, altering timing between the infections from few hours to several weeks. We found that both short‐term and long‐term differences in timing of the two infections resulted in significant, genotype‐specific decrease in bacterial virulence. Second, we developed a mathematical model, parameterized from our experimental results, to predict the implications of sequential infections for epidemiological progression of the disease, and levels of fish population suppression, in an aquaculture setting. Predictions of the model showed that sequential exposure of hosts can decrease the population‐level impact of the bacterial epidemic, primarily through the increased recovery rate of sequentially infected hosts, thereby substantially protecting the population from the detrimental impact of infection. However, these effects depended on bacterial strain–fluke genotype combinations, suggesting the genetic composition of the parasite populations can greatly influence the degree of host suppression. Overall, these results suggest that host infection history can have significant consequences for the impact of infection at host population level, potentially shaping parasite epidemiology, disease dynamics and evolution of virulence in farming environments

Characteristics of children requiring admission to neonatal care and paediatric intensive care before the age of 2 years in England and Wales: A data linkage study

\ua9 Author(s) (or their employer(s)) 2024. Objective: To quantify the characteristics of children admitted to neonatal units (NNUs) and paediatric intensive care units (PICUs) before the age of 2 years. Design: A data linkage study of routinely collected data. Setting: National Health Service NNUs and PICUs in England and Wales Patients: Children born from 2013 to 2018. Interventions: None. Main outcome measure: Admission to PICU before the age of 2 years. Results: A total of 384 747 babies were admitted to an NNU and 4.8% (n=18 343) were also admitted to PICU before the age of 2 years. Approximately half of all children admitted to PICU under the age of 2 years born in the same time window (n=18 343/37 549) had previously been cared for in an NNU. The main reasons for first admission to PICU were cardiac (n=7138) and respiratory conditions (n=5386). Cardiac admissions were primarily from children born at term (n=5146), while respiratory admissions were primarily from children born preterm (<37 weeks\u27 gestational age, n=3550). A third of children admitted to PICU had more than one admission. Conclusions: Healthcare professionals caring for babies and children in NNU and PICU see some of the same children in the first 2 years of life. While some children are following established care pathways (eg, staged cardiac surgery), the small proportion of children needing NNU care subsequently requiring PICU care account for a large proportion of the total PICU population. These differences may affect perceptions of risk for this group of children between NNU and PICU teams

Antibodies and coinfection drive variation in nematode burdens in wild mice

Coinfections with parasitic helminths and microparasites are highly common in nature and can lead to complex within-host interactions between parasite species which can cause negative health outcomes for humans, and domestic and wild animals. Many of these negative health effects worsen with increasing parasite burdens. However, even though many studies have identified several key factors that determine worm burdens across various host systems, less is known about how the immune response interacts with these factors and what the consequences are for the outcome of within-host parasite interactions. We investigated two interacting gastrointestinal parasites of wild wood mice, Heligmosomoides polygyrus (nematode) and Eimeria spp. (coccidia), in order to investigate how host demographic factors, coinfection and the host’s immune response affected parasite burdens and infection probability, and to determine what factors predict parasite-specific and total antibody levels. We found that antibody levels were the only factors that significantly influenced variation in both H. polygyrus burden and infection probability, and Eimeria spp. infection probability. Total faecal IgA was negatively associated with H. polygyrus burden and Eimeria spp. infection, whereas H. polygyrus-specific IgG1 was positively associated with H. polygyrus infection. We further found that the presence of Eimeria spp. had a negative effect on both faecal IgA and H. polygyrus-specific IgG1. Our results show that even in the context of natural demographic and immunological variation amongst individuals, we were able to decipher a role for the host humoral immune response in shaping the within-host interaction between H. polygyrus and Eimeria spp

The drivers of squirrelpox virus dynamics in its grey squirrel reservoir host

Manypathogensofconservationconcerncirculateendemicallywithinnaturalwildlifereservoirhostsanditisimperativetounderstandtheindividualandecologicaldriversofnaturaltransmissiondynamics,ifanythreattoarelatedendangeredspeciesistobeassessed.Ourstudyhighlightsthekeydriversofinfectionandsheddingdynamicsofsquirrelpoxvirus(SQPV)initsreservoirgreysquirrel(Sciurus carolinensis)population.ToclarifySQPV dynamics in this population, longitudinal data from a 16-month mark-recapture study were analysed,combining serology with real-time quantitative PCR to identify periods of acute viraemia and chronic viralshedding. At the population level, we found SQPV infection prevalence, viral load and shedding varied sea-sonally,peakinginautumnandearlyspring.Individually,SQPVwasshowntobeachronicinfectionin>80%ofgreysquirrels,withviralloadspersistingovertimeandboutsofpotentialrecrudescenceorreinfectionoc-curring.AkeyrecurringfactorsignificantlyassociatedwithSQPVinfectionriskwasthepresenceofco-infectingsquirrel adenovirus (ADV). In dual infected squirrels, longitudinal analysis showed that prior ADV viraemiaincreasedthesubsequentSQPVloadintheblood.However,therewasastrong,negativeassociationbetweenpriorADVviraemiaandsubsequentSQPVsheddingfromtheforearm,probablycausedbyADVprolongingtheSQPVacuteviraemicphase,sodelayingonsetofthechronicsheddingphase,andtherebyalteringviralsheddingpatternsoverthetimescalesexaminedhere.Hence,co-circulatingADVinfectionmaybeinvolvedinmediatingboththequantitativelevelsofSQPVinfectionandthetiminganddegreeofsubsequentinfectiousnessofgreysquirrels

A qualitative synthesis of factors influencing maintenance of lifestyle behaviour change in individuals with high cardiovascular risk

Management of cardiovascular risk factors includes commitment from patients to adhere to prescribed medications and adopt healthy lifestyles. Unfortunately many fail to take up and maintain the four key healthy behaviours (not smoking, having a balanced diet, limiting alcohol consumption and being more active). Five factors (beliefs, knowledge, transport and other costs, emotions, and friends and family support) are known to predict uptake of lifestyle behaviour change. The key factors influencing maintenance of healthy lifestyles are not known but would be helpful to support the development of relapse prevention programmes for this population. Our review aimed to clarify the main patient perceived factors thought to influence maintenance of changed healthy lifestyles. ; We performed a systematic review of qualitative observational studies and applied the principles of content synthesis and thematic analysis to extract reported factors (barriers and facilitators) considered by individuals to be influential in maintaining changed healthy lifestyle behaviours. Factors were then organised into an existing framework of higher order categories which was followed by an analysis of the interrelationships between factors to identify key themes. ; Twenty two studies met our inclusion criteria. Participants reported barriers and facilitators within 13 categories, the majority of which were facilitators. The most commonly reported influences were those relating to social support (whether provided formally or informally), beliefs (about the self or the causes and management of poor health, and the value of maintaining lifestyle behaviours), and other psychological factors (including attitude, thinking and coping styles, and problem solving skills). Physical activity was the most commonly investigated behaviour in four categories, but overall, the main barriers and facilitators were related to a range of behaviours. Through analysis of the interrelationships between factors within categories, ‘social support’, ‘education and knowledge’, and ‘beliefs and emotions’ were all considered key themes. ; Our review suggests that for the most part, factors that influence lifestyle change are also important for maintaining healthy behaviours. This indicates that addressing these barriers and facilitators within lifestyle support programmes would also be of value in the longer-term

Immunophenotypic studies of monoclonal gammopathy of undetermined significance

<p>Abstract</p> <p>Background</p> <p>Monoclonal gammopathy of undetermined significance (MGUS) is a common plasma cell dyscrasia, comprising the most indolent form of monoclonal gammopathy. However, approximately 25% of MGUS cases ultimately progress to plasma cell myeloma (PCM) or related diseases. It is difficult to predict which subset of patients will transform. In this study, we examined the immunophenotypic differences of plasma cells in MGUS and PCM.</p> <p>Methods</p> <p>Bone marrow specimens from 32 MGUS patients and 32 PCM patients were analyzed by 4-color flow cytometry, using cluster analysis of ungated data, for the expression of several markers, including CD10, CD19, CD20, CD38, CD45, CD56 and surface and intracellular immunoglobulin light chains.</p> <p>Results</p> <p>All MGUS patients had two subpopulations of plasma cells, one with a "normal" phenotype [CD19(+), CD56(-), CD38(bright +)] and one with an aberrant phenotype [either CD19(-)/CD56(+) or CD19(-)/CD56(-)]. The normal subpopulation ranged from 4.4 to 86% (mean 27%) of total plasma cells. Only 20 of 32 PCM cases showed an identifiable normal subpopulation at significantly lower frequency [range 0–32%, mean 3.3%, p << 0.001]. The plasma cells in PCM were significantly less likely to express CD19 [1/32 (3.1%) vs. 13/29 (45%), p << 0.001] and more likely to express surface immunoglobulin [21/32 (66%) vs. 3/28 (11%), p << 0.001], compared to MGUS. Those expressing CD19 did so at a significantly lower level than in MGUS, with no overlap in mean fluorescence intensities [174 ± 25 vs. 430 ± 34, p << 0.001]. There were no significant differences in CD56 expression [23/32 (72%) vs. 18/29 (62%), p = 0.29], CD45 expression [15/32 (47%) vs. 20/30 (67%), p = 0.10] or CD38 mean fluorescence intensities [6552 ± 451 vs. 6365 ± 420, p = 0.38]. Two of the six MGUS cases (33%) with >90% CD19(-) plasma cells showed progression of disease, whereas none of the cases with >10% CD19(+) plasma cells evolved to PCM.</p> <p>Conclusion</p> <p>MGUS cases with potential for disease progression appeared to lack CD19 expression on >90% of their plasma cells, displaying an immunophenotypic profile similar to PCM plasma cells. A higher relative proportion of CD19(+) plasma cells in MGUS may be associated with a lower potential for disease progression.</p