Routes to diagnosis and the association with the prognosis in patients with cancer – A nationwide register-based cohort study in Denmark

Background: The prognosis of cancer is related to how the cancer is identified, and where in the healthcare system the patient presents, i.e. routes to diagnosis (RtD). We aimed to describe the RtD for patients diagnosed with cancer in Denmark by using routinely collected register-based data and to investigate the association between RtD and prognosis measured as one-year all-cause mortality. / Methods: We conducted a population-based national cohort study by linking routinely collected Danish registry data. We categorised each patient into one of eight specified RtD based on an algorithm using a stepwise logic decision process. We described the proportions of patients with cancer diagnosed by different RtD. We examined associations between RtD and one-year all-cause mortality using logistic regression models adjusting for sex, age, cancer type, year of diagnosis, region of residence, and comorbidity. / Results: We included 144,635 cancers diagnosed in 139,023 patients in 2014–2017. The most common RtD were cancer patient pathway from primary care (45.9 %), cancer patient pathway from secondary care (20.0 %), unplanned hospital admission (15.8 %), and population-based screening (7.5 %). The one-year mortality ranged from 1.4 % in screened patients to 53.0 % in patients diagnosed through unplanned hospital admission. Patients with an unplanned admission were more likely to die within the first year after diagnosis (OR = 3.38 (95 %CI: 3.24–3.52)) compared to patients diagnosed through the cancer patient pathway from primary care. / Conclusion: The majority of cancer patients were diagnosed through a cancer patient pathway. The RtD were associated with the prognosis, and the prognosis was worst in patients diagnosed through unplanned admission. The study suggests that linking routinely collected registry data could enable a national framework for RtD, which could serve to identify variations across patient-, health-, and system-related and healthcare factors. This information could be used in future research investigating markers for monitoring purposes

Assessing how routes to diagnosis vary by the age of patients with cancer: a nationwide register-based cohort study in Denmark

BACKGROUND: Older patients with cancer have poorer prognosis compared to younger patients. Moreover, prognosis is related to how cancer is identified, and where in the healthcare system patients present, i.e. routes to diagnosis (RtD). We investigated whether RtD varied by patients' age. METHODS: This population-based national cohort study used Danish registry data. Patients were categorized into age groups and eight mutually exclusive RtD. We employed multinomial logistic regressions adjusted for sex, region, diagnosis year, cohabitation, education, income, immigration status and comorbidities. Screened and non-screened patients were analysed separately. RESULTS: The study included 137,876 patients. Both younger and older patients with cancer were less likely to get diagnosed after a cancer patient pathways referral from primary care physician compared to middle-aged patients. Older patients were more likely to get diagnosed via unplanned admission, death certificate only, and outpatient admission compared to younger patients. The patterns were similar across comorbidity levels. CONCLUSIONS: RtD varied by age groups, and middle-aged patients were the most likely to get diagnosed after cancer patient pathways with referral from primary care. Emphasis should be put on raising clinicians' awareness of cancer being the underlying cause of symptoms in both younger patients and in older patients

Rectal swabs as a viable alternative to faecal sampling for the analysis of gut microbiota functionality and composition

Faecal or biopsy samples are frequently used to analyse the gut microbiota, but issues remain with the provision and collection of such samples. Rectal swabs are widely-utilised in clinical practice and previous data demonstrate their potential role in microbiota analyses; however, studies to date have been heterogenous, and there is a particular lack of data concerning the utility of swabs for the analysis of the microbiota’s functionality and metabolome. We compared paired stool and rectal swab samples from healthy individuals to investigate whether rectal swabs are a reliable proxy for faecal sampling. There were no significant differences in alpha and beta diversity measures between swab and faecal samples, and inter-subject variability was preserved. Additionally, no significant differences were demonstrated in abundance of major annotated phyla. Inferred gut functionality using Tax4Fun2 showed excellent correlation between the two sampling techniques (Pearson’s coefficient r = 0.9217, P  < 0.0001). Proton nuclear magnetic resonance ( 1 H NMR) spectroscopy enabled the detection of 20 metabolites with good correlation between rectal swab and faecal samples for butyrate, succinate and 5-aminovalerate relative abundances, though more variable degrees of association for other identified metabolites. These data support the utility of rectal swabs in both compositional and functional analyses of the gut microbiota

Self-regulation and the foraging gene (PRKG1) in humans

We would like to thank Dr. Sara Mostafavi (University of British Columbia) for directing us to the CMC website regarding gene expression for rs13499 and for statistical advice. This work was supported by NSERC Discovery funds to JD and a Canadian Institute for Advanced Research award to MS.Peer reviewedPostprin

Improved change detection with nearby hands

Recent studies have suggested altered visual processing for objects that are near the hands. We present three experiments that test whether an observer’s hands near the display facilitate change detection. While performing the task, observers placed both hands either near or away from the display. When their hands were near the display, change detection performance was more accurate and they held more items in visual short-term memory (experiment 1). Performance was equally improved for all regions across the entire display, suggesting a stronger attentional engagement over all visual stimuli regardless of their relative distances from the hands (experiment 2). Interestingly, when only one hand was placed near the display, we found no facilitation from the left hand and a weak facilitation from the right hand (experiment 3). Together, these data suggest that the right hand is the main source of facilitation, and both hands together produce a nonlinear boost in performance (superadditivity) that cannot be explained by either hand alone. In addition, the presence of the right hand biased observers to attend to the right hemifield first, resulting in a right-bias in change detection performance (experiments 2 and 3)

Alertness and visuospatial attention in clinical depression

<p>Abstract</p> <p>Background</p> <p>Cognitive deficits are a substantial burden in clinical depression. The present study considered dysfunction in the right-hemispheric attention network in depression, examining alertness and visuospatial attention.</p> <p>Methods</p> <p>Three computerized visuospatial attention tests and an alertness test were administered to 16 depressive patients and 16 matched healthy controls.</p> <p>Results</p> <p>Although no significant group effect was observed, alertness predicted reduced visuospatial performance in the left hemifield. Furthermore, sad mood showed a trend towards predicting left visual field omissions.</p> <p>Conclusions</p> <p>Decreased alertness may lead to lower left hemifield visuospatial attention; this mechanism may be responsible for a spatial bias to the right side in depression, even though treatment of depression and anxiety may reduce this cognitive deficit.</p

Exploring the Relationship between Semantics and Space

The asymmetric distribution of human spatial attention has been repeatedly documented in both patients and healthy controls. Biases in the distribution of attention and/or in the mental representation of space may also affect some aspects of language processing. We investigated whether biases in attention and/or mental representation of space affect semantic representations. In particular, we investigated whether semantic judgments could be modulated by the location in space where the semantic information was presented and the role of the left and right parietal cortices in this task. Healthy subjects were presented with three pictures arranged horizontally (one middle and two outer pictures) of items belonging to the same semantic category. Subjects were asked to indicate the spatial position in which the semantic distance between the outer and middle pictures was smaller. Subjects systematically overestimated the semantic distance of items presented in the right side of space. We explored the neural correlates underpinning this bias using rTMS over the left and right parietal cortex. rTMS of the left parietal cortex selectively reduced this rightward bias. Our findings suggest the existence of an attentional and/or mental representational bias in semantic judgments, similar to that observed for the processing of space and numbers. Spatial manipulation of semantic material results in the activation of specialised attentional resources located in the left hemisphere

Action Without Awareness: Reaching to an Object You Do Not Remember Seeing

BACKGROUND: Previous work by our group has shown that the scaling of reach trajectories to target size is independent of obligatory awareness of that target property and that "action without awareness" can persist for up to 2000 ms of visual delay. In the present investigation we sought to determine if the ability to scale reaching trajectories to target size following a delay is related to the pre-computing of movement parameters during initial stimulus presentation or the maintenance of a sensory (i.e., visual) representation for on-demand response parameterization. METHODOLOGY/PRINCIPAL FINDINGS: Participants completed immediate or delayed (i.e., 2000 ms) perceptual reports and reaching responses to different sized targets under non-masked and masked target conditions. For the reaching task, the limb associated with a trial (i.e., left or right) was not specified until the time of response cuing: a manipulation that prevented participants from pre-computing the effector-related parameters of their response. In terms of the immediate and delayed perceptual tasks, target size was accurately reported during non-masked trials; however, for masked trials only a chance level of accuracy was observed. For the immediate and delayed reaching tasks, movement time as well as other temporal kinematic measures (e.g., times to peak acceleration, velocity and deceleration) increased in relation to decreasing target size across non-masked and masked trials. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that speed-accuracy relations were observed regardless of whether participants were aware (i.e., non-masked trials) or unaware (i.e., masked trials) of target size. Moreover, the equivalent scaling of immediate and delayed reaches during masked trials indicates that a persistent sensory-based representation supports the unconscious and metrical scaling of memory-guided reaching

Dynamic Spatial Coding within the Dorsal Frontoparietal Network during a Visual Search Task

To what extent are the left and right visual hemifields spatially coded in the dorsal frontoparietal attention network? In many experiments with neglect patients, the left hemisphere shows a contralateral hemifield preference, whereas the right hemisphere represents both hemifields. This pattern of spatial coding is often used to explain the right-hemispheric dominance of lesions causing hemispatial neglect. However, pathophysiological mechanisms of hemispatial neglect are controversial because recent experiments on healthy subjects produced conflicting results regarding the spatial coding of visual hemifields. We used an fMRI paradigm that allowed us to distinguish two attentional subprocesses during a visual search task. Either within the left or right hemifield subjects first attended to stationary locations (spatial orienting) and then shifted their attentional focus to search for a target line. Dynamic changes in spatial coding of the left and right hemifields were observed within subregions of the dorsal front-parietal network: During stationary spatial orienting, we found the well-known spatial pattern described above, with a bilateral hemifield representation in the right hemisphere and a contralateral preference in the left hemisphere. However, during search, the right hemisphere had a contralateral preference and the left hemisphere equally represented both hemifields. This finding leads to novel perspectives regarding models of visuospatial attention and hemispatial neglect