Cost-effectiveness analysis of 3-D computerized tomography colonography versus optical colonoscopy for imaging symptomatic gastroenterology patients.

BACKGROUND: When symptomatic gastroenterology patients have an indication for colonic imaging, clinicians have a choice between optical colonoscopy (OC) and computerized tomography colonography with three-dimensional reconstruction (3-D CTC). 3-D CTC provides a minimally invasive and rapid evaluation of the entire colon, and it can be an efficient modality for diagnosing symptoms. It allows for a more targeted use of OC, which is associated with a higher risk of major adverse events and higher procedural costs. A case can be made for 3-D CTC as a primary test for colonic imaging followed if necessary by targeted therapeutic OC; however, the relative long-term costs and benefits of introducing 3-D CTC as a first-line investigation are unknown. AIM: The aim of this study was to assess the cost effectiveness of 3-D CTC versus OC for colonic imaging of symptomatic gastroenterology patients in the UK NHS. METHODS: We used a Markov model to follow a cohort of 100,000 symptomatic gastroenterology patients, aged 50 years or older, and estimate the expected lifetime outcomes, life years (LYs) and quality-adjusted life years (QALYs), and costs (£, 2010-2011) associated with 3-D CTC and OC. Sensitivity analyses were performed to assess the robustness of the base-case cost-effectiveness results to variation in input parameters and methodological assumptions. RESULTS: 3D-CTC provided a similar number of LYs (7.737 vs 7.739) and QALYs (7.013 vs 7.018) per individual compared with OC, and it was associated with substantially lower mean costs per patient (£467 vs £583), leading to a positive incremental net benefit. After accounting for the overall uncertainty, the probability of 3-D CTC being cost effective was around 60 %, at typical willingness-to-pay values of £20,000-£30,000 per QALY gained. CONCLUSION: 3-D CTC is a cost-saving and cost-effective option for colonic imaging of symptomatic gastroenterology patients compared with OC

The co-development of a linguistic and culturally tailored tele-retinopathy screening intervention for immigrants living with diabetes from China and African-Caribbean countries in Ottawa, Canada

Background: Diabetic retinopathy is a sight-threatening ocular complication of diabetes. Screening is an effective way to reduce severe complications, but screening attendance rates are often low, particularly for newcomers and immigrants to Canada and people from cultural and linguistic minority groups. Building on previous work, in partnership with patient and health system stakeholders, we co-developed a linguistically and culturally tailored tele-retinopathy screening intervention for people living with diabetes who recently immigrated to Canada from either China or African-Caribbean countries. Methods: Following an environmental scan of diabetes eye care pathways in Ottawa, we conducted co-development workshops using a nominal group technique to create and prioritize personas of individuals requiring screening and identify barriers to screening that each persona may face. Next, we used the Theoretical Domains Framework to categorize the barriers/enablers and then mapped these categories to potential evidence-informed behaviour change techniques. Finally with these techniques in mind, participants prioritized strategies and channels of delivery, developed intervention content, and clarified actions required by different actors to overcome anticipated intervention delivery barriers. Results: We carried out iterative co-development workshops with Mandarin and French-speaking individuals living with diabetes (i.e., patients in the community) who immigrated to Canada from China and African-Caribbean countries (n = 13), patient partners (n = 7), and health system partners (n = 6) recruited from community health centres in Ottawa. Patients in the community co-development workshops were conducted in Mandarin or French. Together, we prioritized five barriers to attending diabetic retinopathy screening: language (TDF Domains: skills, social influences), retinopathy familiarity (knowledge, beliefs about consequences), physician barriers regarding communication for screening (social influences), lack of publicity about screening (knowledge, environmental context and resources), and fitting screening around other activities (environmental context and resources). The resulting intervention included the following behaviour change techniques to address prioritized local barriers: information about health consequence, providing instructions on how to attend screening, prompts/cues, adding objects to the environment, social support, and restructuring the social environment. Operationalized delivery channels incorporated language support, pre-booking screening and sending reminders, social support via social media and community champions, and providing using flyers and videos as delivery channels. Conclusion: Working with intervention users and stakeholders, we co-developed a culturally and linguistically relevant tele-retinopathy intervention to address barriers to attending diabetic retinopathy screening and increase uptake among two under-served groups

Adjusting for multiple prognostic factors in the analysis of randomised trials

Background: When multiple prognostic factors are adjusted for in the analysis of a randomised trial, it is unclear (1) whether it is necessary to account for each of the strata, formed by all combinations of the prognostic factors (stratified analysis), when randomisation has been balanced within each stratum (stratified randomisation), or whether adjusting for the main effects alone will suffice, and (2) the best method of adjustment in terms of type I error rate and power, irrespective of the randomisation method. Methods: We used simulation to (1) determine if a stratified analysis is necessary after stratified randomisation, and (2) to compare different methods of adjustment in terms of power and type I error rate. We considered the following methods of analysis: adjusting for covariates in a regression model, adjusting for each stratum using either fixed or random effects, and Mantel-Haenszel or a stratified Cox model depending on outcome. Results: Stratified analysis is required after stratified randomisation to maintain correct type I error rates when (a) there are strong interactions between prognostic factors, and (b) there are approximately equal number of patients in each stratum. However, simulations based on real trial data found that type I error rates were unaffected by the method of analysis (stratified vs unstratified), indicating these conditions were not met in real datasets. Comparison of different analysis methods found that with small sample sizes and a binary or time-to-event outcome, most analysis methods lead to either inflated type I error rates or a reduction in power; the lone exception was a stratified analysis using random effects for strata, which gave nominal type I error rates and adequate power. Conclusions: It is unlikely that a stratified analysis is necessary after stratified randomisation except in extreme scenarios. Therefore, the method of analysis (accounting for the strata, or adjusting only for the covariates) will not generally need to depend on the method of randomisation used. Most methods of analysis work well with large sample sizes, however treating strata as random effects should be the analysis method of choice with binary or time-to-event outcomes and a small sample size

The risks and rewards of covariate adjustment in randomized trials: an assessment of 12 outcomes from 8 studies

Adjustment for prognostic covariates can lead to increased power in the analysis of randomized trials. However, adjusted analyses are not often performed in practice

Digital IAPT: the effectiveness & cost-effectiveness of internet-delivered interventions for depression and anxiety disorders in the Improving Access to Psychological Therapies programme: study protocol for a randomised control trial

BACKGROUND: Depression and anxiety are common mental health disorders worldwide. The UK's Improving Access to Psychological Therapies (IAPT) programme is part of the National Health Service (NHS) designed to provide a stepped care approach to treating people with anxiety and depressive disorders. Cognitive Behavioural Therapy (CBT) is widely used, with computerised and internet-delivered cognitive behavioural therapy (cCBT and iCBT, respectively) being a suitable IAPT approved treatment alternative for step 2, low- intensity treatment. iCBT has accumulated a large empirical base for treating depression and anxiety disorders. However, the cost-effectiveness and impact of these interventions in the longer-term is not routinely assessed by IAPT services. The current study aims to evaluate the clinical and cost-effectiveness of internet-delivered interventions for symptoms of depression and anxiety disorders in IAPT. METHODS: The study is a parallel-groups, randomised controlled trial examining the effectiveness and cost-effectiveness of iCBT interventions for depression and anxiety disorders, against a waitlist control group. The iCBT treatments are of 8 weeks duration and will be supported by regular post-session feedback by Psychological Wellbeing Practitioners. Assessments will be conducted at baseline, during, and at the end of the 8-week treatment and at 3, 6, 9, and 12-month follow-up. A diagnostic interview will be employed at baseline and 3-month follow-up. Participants in the waitlist control group will complete measures at baseline and week 8, at which point they will receive access to the treatment. All adult users of the Berkshire NHS Trust IAPT Talking Therapies Step 2 services will be approached to participate and measured against set eligibility criteria. Primary outcome measures will assess anxiety and depressive symptoms using the GAD-7 and PHQ-9, respectively. Secondary outcome measures will allow for the evaluation of long-term outcomes, mediators and moderators of outcome, and cost-effectiveness of treatment. Analysis will be conducted on a per protocol and intention-to-treat basis. DISCUSSION: This study seeks to evaluate the immediate and longer-term impact, as well as the cost effectiveness of internet-delivered interventions for depression and anxiety. This study will contribute to the already established literature on internet-delivered interventions worldwide. The study has the potential to show how iCBT can enhance service provision, and the findings will likely be generalisable to other health services. TRIAL REGISTRATION: Current Controlled Trials ISRCTN ISRCTN91967124. DOI: https://doi.org/10.1186/ISRCTN91967124 . Web: http://www.isrctn.com/ISRCTN91967124 . Clinicaltrials.gov : NCT03188575. Trial registration date: June 8, 2017 (prospectively registered)

Influence of Short-Term Glucocorticoid Therapy on Regulatory T Cells In Vivo

Background: Pre- and early clinical studies on patients with autoimmune diseases suggested that induction of regulatory T(Treg) cells may contribute to the immunosuppressive effects of glucocorticoids(GCs). Objective: We readdressed the influence of GC therapy on Treg cells in immunocompetent human subjects and naı¨ve mice. Methods: Mice were treated with increasing doses of intravenous dexamethasone followed by oral taper, and Treg cells in spleen and blood were analyzed by FACS. Sixteen patients with sudden hearing loss but without an inflammatory disease received high-dose intravenous prednisolone followed by stepwise dose reduction to low oral prednisolone. Peripheral blood Treg cells were analyzed prior and after a 14 day GC therapy based on different markers. Results: Repeated GC administration to mice for three days dose-dependently decreased the absolute numbers of Treg cells in blood (100 mg dexamethasone/kg body weight: 2.861.86104 cells/ml vs. 336116104 in control mice) and spleen (dexamethasone: 2.861.96105/spleen vs. 956226105/spleen in control mice), which slowly recovered after 14 days taper in spleen but not in blood. The relative frequency of FOXP3+ Treg cells amongst the CD4+ T cells also decreased in a dose dependent manner with the effect being more pronounced in blood than in spleen. The suppressive capacity of Treg cells was unaltered by GC treatment in vitro. In immunocompetent humans, GCs induced mild T cell lymphocytosis. However, it did not change the relative frequency of circulating Treg cells in a relevant manner, although there was some variation depending on the definition of the Treg cells (FOXP3+: 4.061.5% vs 3.461.5%*; AITR+: 0.660.4 vs 0.560.3%, CD127low: 4.061.3 vs 5.063.0%* and CTLA4+: 13.8611.5 vs 15.6612.5%; * p,0.05). Conclusion: Short-term GC therapy does not induce the hitherto supposed increase in circulating Treg cell frequency, neither in immunocompetent humans nor in mice. Thus, it is questionable that the clinical efficacy of GCs is achieved by modulating Treg cell numbers

The Distribution of Toxoplasma gondii Cysts in the Brain of a Mouse with Latent Toxoplasmosis: Implications for the Behavioral Manipulation Hypothesis

reportedly manipulates rodent behavior to enhance the likelihood of transmission to its definitive cat host. The proximate mechanisms underlying this adaptive manipulation remain largely unclear, though a growing body of evidence suggests that the parasite-entrained dysregulation of dopamine metabolism plays a central role. Paradoxically, the distribution of the parasite in the brain has received only scant attention. at six months of age and examined 18 weeks later. The cysts were distributed throughout the brain and selective tropism of the parasite toward a particular functional system was not observed. Importantly, the cysts were not preferentially associated with the dopaminergic system and absent from the hypothalamic defensive system. The striking interindividual differences in the total parasite load and cyst distribution indicate a probabilistic nature of brain infestation. Still, some brain regions were consistently more infected than others. These included the olfactory bulb, the entorhinal, somatosensory, motor and orbital, frontal association and visual cortices, and, importantly, the hippocampus and the amygdala. By contrast, a consistently low incidence of tissue cysts was recorded in the cerebellum, the pontine nuclei, the caudate putamen and virtually all compact masses of myelinated axons. Numerous perivascular and leptomeningeal infiltrations of inflammatory cells were observed, but they were not associated with intracellular cysts. distribution stems from uneven brain colonization during acute infection and explains numerous behavioral abnormalities observed in the chronically infected rodents. Thus, the parasite can effectively change behavioral phenotype of infected hosts despite the absence of well targeted tropism

Understanding How University Students Use Perceptions of Consent, Wantedness, and Pleasure in Labeling Rape.

While the lack of consent is the only determining factor in considering whether a situation is rape or not, there is sufficient evidence that participants conflate wantedness with consent and pleasurableness with wantedness. Understanding how people appraise sexual scenarios may form the basis to develop appropriate educational packages. We conducted two large-scale qualitative studies in two UK universities in which participants read vignettes describing sexual encounters that were consensual or not, wanted or unwanted and pleasurable or not pleasurable. Participants provided free-text responses as to whether they perceived the scenarios to be rape or not and why they made these judgments. The second study replicated the results of the first and included a condition where participants imagined themselves as either the subject or initiator of the sexual encounter. The results indicate that a significant portion of our participants held attitudes reflecting rape myths and tended to blame the victim. Participants used distancing language when imagining themselves in the initiator condition. Participants indicated that they felt there were degrees of how much a scenario reflected rape rather than it simply being a dichotomy (rape or not). Such results indicate a lack of understanding of consent and rape and highlight avenues of potential educational materials for schools, universities or jurors

Hippocampal - diencephalic - cingulate networks for memory and emotion: An anatomical guide

This review brings together current knowledge from tract tracing studies to update and reconsider those limbic connections initially highlighted by Papez for their presumed role in emotion. These connections link hippocampal and parahippocampal regions with the mammillary bodies, the anterior thalamic nuclei, and the cingulate gyrus, all structures now strongly implicated in memory functions. An additional goal of this review is to describe the routes taken by the various connections within this network. The original descriptions of these limbic connections saw their interconnecting pathways forming a serial circuit that began and finished in the hippocampal formation. It is now clear that with the exception of the mammillary bodies, these various sites are multiply interconnected with each other, including many reciprocal connections. In addition, these same connections are topographically organised, creating further subsystems. This complex pattern of connectivity helps explain the difficulty of interpreting the functional outcome of damage to any individual site within the network. For these same reasons, Papez’s initial concept of a loop beginning and ending in the hippocampal formation needs to be seen as a much more complex system of hippocampal–diencephalic–cingulate connections. The functions of these multiple interactions might be better viewed as principally providing efferent information from the posterior medial temporal lobe. Both a subcortical diencephalic route (via the fornix) and a cortical cingulate route (via retrosplenial cortex) can be distinguished. These routes provide indirect pathways for hippocampal interactions with prefrontal cortex, with the preponderance of both sets of connections arising from the more posterior hippocampal regions. These multi-stage connections complement the direct hippocampal projections to prefrontal cortex, which principally arise from the anterior hippocampus, thereby creating longitudinal functional differences along the anterior–posterior plane of the hippocampus