How do people interpret information about colorectal cancer screening: observations from a think‐aloud study

Background

The English NHS Bowel Cancer Screening Programme biennially invites individuals aged 60–74 to participate in screening. The booklet, ‘Bowel Cancer Screening: The Facts'' accompanies this invitation. Its primary aim is to inform potential participants about the aims, advantages and disadvantages of colorectal cancer screening.

Objective

To provide detailed commentary on how individuals process the information contained within ‘The Facts’ booklet.

Design, setting and participants

This study comprised of 18 interviews with individuals aged 45–60 and used a ‘think‐aloud’ paradigm in which participants read aloud the booklet. Participant utterances (verbal statements made in response to researcher‐led prompts) were transcribed and analysed using a combination of content and thematic analysis.

Results

A total of 776 coded utterances were analysed (mean = 43.1 per person; range = 8–95). While overall comprehension was satisfactory, several problem areas were identified such as the use of complex unfamiliar terminology and the presentation of numerical information. Specific sections such as colonoscopy risk information evoked negative emotional responses. Participants made several suggestions for ways in which comprehension might be improved.

Conclusion

Public perceptions of the NHS Bowel Cancer Screening Programme information materials indicated that specific aspects of the booklet were difficult to process. These materials may be an appropriate target to improve public understanding of the aims, benefits and disadvantages of colorectal cancer screening. These findings will contribute to a broader NIHR‐funded project that aims to design a supplementary ‘gist‐based’ information leaflet suitable for low literacy populations.     

Enhanced Dopamine-Dependent Hippocampal Plasticity after Single MK-801 Application

Dopaminergic hyperfunction and N-methyl-D-aspartate receptor (NMDAR) hypofunction have both been implicated in psychosis. Dopamine-releasing drugs and NMDAR antagonists replicate symptoms associated with psychosis in healthy humans and exacerbate symptoms in patients with schizophrenia. Though hippocampal dysfunction contributes to psychosis, the impact of NMDAR hypofunction on hippocampal plasticity remains poorly understood. Here, we used an NMDAR antagonist rodent model of psychosis to investigate hippocampal long-term potentiation (LTP). We found that single systemic NMDAR antagonism results in a region-specific, presynaptic LTP at hippocampal CA1-subiculum synapses that is induced by activation of D1/D5 dopamine receptors and modulated by L-type voltage-gated Ca²⁺ channels. Thereby, our findings may provide a cellular mechanism how NMDAR antagonism can lead to an enhanced hippocampal output causing activation of the hippocampus-ventral tegmental area-loop and overdrive of the dopamine system.     

Serotonin Transporter and Tryptophan Hydroxylase Gene Variations Mediate Working Memory Deficits of Cocaine Users

Cocaine users consistently develop working memory (WM) impairments but the mediating molecular mechanisms are unknown so far. Recent evidence suggests that the serotonin (5-HT) system is altered by chronic cocaine use, while also being involved in WM processing. Thus, we investigated the effects of genetic variations impacting 5-HT activity and of peripheral 5-HT transporter (5-HTT) mRNA expression on WM performance in cocaine users and stimulant naive controls. Two hundred twenty participants (126 cocaine users, 94 controls) were assessed with visuospatial, spatial, and verbal WM tasks, genotyped for the length polymorphism in the promoter region of the 5-HTT (5-HTTLPR), the variable number of tandem repeats in the second intron of the 5-HTT (VNTR In2), two single-nucleotide polymorphisms (rs4570625 and rs1386497) in the tryptophan hydroxylase-2 (TPH2) gene and quantified for peripheral 5-HTT mRNA expression in whole-blood samples. Several significant gene × environment interactions between 5-HT genotypes and cocaine use on WM emerged: in cocaine users, the long/long (5-HTTLPR), 9+10/9+10 (VNTR In2) and C/C (TPH2 rs1386497) genotypes were risk alleles for WM impairments, whereas in healthy controls these polymorphisms were associated with improved WM performance. Analogously, high 5-HTT mRNA levels were associated with worse executive WM performance in cocaine users but with increased performance in controls. These gene × environment interactions suggest that the 5-HT system has an important role in the development of cognitive deficits in chronic cocaine users. Hence, pharmacological compounds targeting 5-HT neurotransmission might be promising for the treatment of cognitive deficits in cocaine dependence.     

Risk-Taking in Disorders of Natural and Drug Rewards: Neural Correlates and Effects of Probability,Valence, and Magnitude

Pathological behaviors toward drugs and food rewards have underlying commonalities. Risk-taking has a fourfold pattern varying as a function of probability and valence leading to the nonlinearity of probability weighting with overweighting of small probabilities and underweighting of large probabilities. Here we assess these influences on risk-taking in patients with pathological behaviors toward drug and food rewards and examine structural neural correlates of nonlinearity of probability weighting in healthy volunteers. In the anticipation of rewards, subjects with binge eating disorder show greater risk-taking, similar to substance-use disorders. Methamphetamine-dependent subjects had greater nonlinearity of probability weighting along with impaired subjective discrimination of probability and reward magnitude. Ex-smokers also had lower risk-taking to rewards compared with non-smokers. In the anticipation of losses, obesity without binge eating had a similar pattern to other substance-use disorders. Obese subjects with binge eating also have impaired discrimination of subjective value similar to that of the methamphetamine-dependent subjects. Nonlinearity of probability weighting was associated with lower gray matter volume in dorsolateral and ventromedial prefrontal cortex and orbitofrontal cortex in healthy volunteers. Our findings support a distinct subtype of binge eating disorder in obesity with similarities in risk-taking in the reward domain to substance use disorders. The results dovetail with the current approach of defining mechanistically based dimensional approaches rather than categorical approaches to psychiatric disorders. The relationship to risk probability and valence may underlie the propensity toward pathological behaviors toward different types of rewards.     

Pharmacosimulation of delays and interruptions during administration of tirofiban: a systematic comparison between EU and US dosage regimens

Journal of Thrombosis and Thrombolysis - Tirofiban is a glycoproteine (GP) IIb/IIIa receptor antagonist, which inhibits platelet-platelet aggregation and is a potential adjunctive antithrombotic...     

Latest culture techniques: cracking the secrets of bone marrow to mass-produce erythrocytes and platelets ex vivo

Since the dawn of medicine, scientists have carefully observed, modeled and interpreted the human body to improve healthcare. At the beginning there were drawings and paintings, now there is three-dimensional modeling. Moving from two-dimensional cultures and towards complex and relevant biomaterials, tissue-engineering approaches have been developed in order to create three-dimensional functional mimics of native organs. The bone marrow represents a challenging organ to reproduce because of its structure and composition that confer it unique biochemical and mechanical features to control hematopoiesis. Reproducing the human bone marrow niche is instrumental to answer the growing demand for human erythrocytes and platelets for fundamental studies and clinical applications in transfusion medicine. In this review, we discuss the latest culture techniques and technological approaches to obtain functional platelets and erythrocytes ex vivo. This is a rapidly evolving field that will define the future of targeted therapies for thrombocytopenia and anemia, but also a long-term promise for new approaches to the understanding and cure of hematologic diseases.     

Dose-Dependent Effect of Renin-Angiotensin System Blockade Following Transcatheter Aortic Valve Replacement

BackgroundThere is growing body of evidence from retrospective studies that renin-angiotensin system (RAS) blockade is associated with improved outcome after transcatheter aortic valve replacement (TAVR). However, it remains unknown whether the effect of RAS blockade is dose dependent. The current study sought to assess the dose-dependent effect of RAS blockade on survival and left-ventricular (LV) remodelling after TAVR.MethodsPatients who were enrolled into our observational TAVR study at our institution were retrospectively assessed according to different doses of RAS blockade: group 1 (no RAS blockade), group 2 (25% of maximum daily dose), group 3 (50% of maximum daily dose), and group 4 (full daily dose).ResultsA total of 323 patients between January 2015 and September 2019 were included. Patients with higher doses of RAS blockade showed a trend toward higher overall survival at 3-year follow-up (56% with no RAS blockade vs 66% with the 25% dose vs 79% with the 50% dose vs 78% with the full dose; P = 0.063). After adjustment for baseline characteristics, the difference in survival was significant (P = 0.042). Besides New York Heart Association class and left-ventricular ejection fraction (LVEF), RAS blockade dose was identified as independent predictor for all-cause mortality (hazard ratio [HR] 0.72; 95% confidence interval [CI], 0.54-0.97; P = 0.03). With respect to LV remodelling, a significantly larger reduction of LV mass index was observed during the follow-up with higher doses of RAS blockade.ConclusionsThe current study showed that the impact of RAS blockade treatment on clinical outcome and LV remodelling after TAVR is dose dependent.     

Novel Z Scores to Correct Biases Due to Ventricular Volume Indexing to Body Surface Area in Adolescents and Young Adults

BackgroundReference values for cardiac magnetic resonance imaging (cMRI) in children and young adults are scarce. This leads to risk stratification of patients with congenital heart diseases being based on volumes indexed to body surface area (BSA). We aimed to produce cMRI Z score equations for ventricular volumes in children and young adults and to test whether indexing to BSA resulted in an incorrect assessment of ventricular dilation according to sex, body composition, and growth.MethodsWe retrospectively included 372 subjects aged < 26 years with either normal hearts or conditions with no impact on ventricular volumes (reference group), and 205 subjects with repaired tetralogy of Fallot (TOF) aged < 26 years. We generated Z score equations by means of multivariable regression modelling. Right ventricular dilation was assessed with the use of Z scores and compared with indexing to BSA in TOF subjects.ResultsVentricular volume Z scores were independent from age, sex, and anthropometric measurements, although volumes indexed to BSA showed significant residual association with sex and body size. In TOF subjects, indexing overestimated dilation in growing children and underestimated dilation in female compared with male subjects, and in overweight compared with lean subjects.ConclusionsIndexed ventricular volumes measured with cMRI did not completely adjust for body size and resulted in a differential error in the assessment of ventricular dilation according to sex and body size. Our proposed Z score equations solved this problem. Future studies should evaluate if ventricular volumes expressed as Z scores have a better prognostic value than volumes indexed to BSA.