The CRISP colorectal cancer risk prediction tool: an exploratory study using simulated consultations in Australian primary care

BACKGROUND: In Australia, screening for colorectal cancer (CRC) with colonoscopy is meant to be reserved for people at increased risk, however, currently there is a mismatch between individuals' risk of CRC and the type of CRC screening they receive. This paper describes the development and optimisation of a Colorectal cancer RISk Prediction tool ('CRISP') for use in primary care. The aim of the CRISP tool is to increase risk-appropriate CRC screening. METHODS: CRISP development was informed by previous experience with developing risk tools for use in primary care and a systematic review of the evidence. A CRISP prototype was used in simulated consultations by general practitioners (GPs) with actors as patients. GPs were interviewed to explore their experience of using CRISP, and practice nurses (PNs) and practice managers (PMs) were interviewed after a demonstration of CRISP. Transcribed interviews and video footage of the 'consultations' were qualitatively analyzed. Themes arising from the data were mapped onto Normalization Process Theory (NPT). RESULTS: Fourteen GPs, nine PNs and six PMs were recruited from 12 clinics. Results were described using the four constructs of NPT: 1) Coherence: Clinicians understood the rationale behind CRISP, particularly since they were familiar with using risk tools for other conditions; 2) Cognitive participation: GPs welcomed the opportunity CRISP provided to discuss healthy and unhealthy behaviors with their patients, but many GPs challenged the screening recommendation generated by CRISP; 3) Collective Action: CRISP disrupted clinician-patient flow if the GP was less comfortable with computers. GP consultation time was a major implementation barrier and overall consensus was that PNs have more capacity and time to use CRISP effectively; 4) Reflexive monitoring: Limited systematic monitoring of new interventions is a potential barrier to the sustainable embedding of CRISP. CONCLUSIONS: CRISP has the potential to improve risk-appropriate CRC screening in primary care but was considered more likely to be successfully implemented as a nurse-led intervention.This study was funded by a National Health and Medical Research Council (NHMRC) Centre for Research Excellence grant (APP1042021). M Pirotta is supported by an NHMRC Career Development Fellowship. JD Emery is supported by an NHMRC Practitioner Fellowship. FM Walter is supported by a NIHR Clinician Scientist award

Should I Take Aspirin? (SITA): RCT of a decision aid for cancer chemoprevention.

Background Australian guidelines recommend that all people aged 50-70 years old consider taking low-dose aspirin to reduce the risk of colorectal cancer (CRC). Aim To determine the effect of a consultation with a researcher in general practice using a decision aid about taking low-dose aspirin to prevent CRC on informed decision-making and low-dose aspirin uptake compared to a general CRC prevention brochure. Design and Setting Individually randomised controlled trial in six general practices in Victoria, Australia, from October 2020 to March 2021. Method Patients aged 50-70 years attending a general practitioner (GP) were recruited consecutively. The intervention was a consultation using a decision aid to discuss taking aspirin to reduce CRC risk; control consultations discussed reducing CRC risk generally. The self-reported co-primary outcomes were informed choices about taking aspirin at one month and low-dose aspirin uptake at six months. Results 261 participants (86% of eligible patients) were randomised into trial arms (129 intervention, 132 control). 17.7% (20/113) of intervention and 7.6% (9/118) control participants reported making an informed choice at one month, an estimated 9.1% (95% CI 0.29% to 18.5) between-arm difference in proportions [odds ratio (OR) 2.47 (97.5% CI:0.94 to 6.52) p=0.074]. The proportions of individuals who reported using aspirin at six months were: 10.2% (12/118) intervention vs 13.8% (16/116) control (estimated between-arm difference: -4.0% (95% CI: -13.5 to 5.5); [OR= 0.68 (97.5% CI:0.27 to 1.70), p= 0.692]. Conclusion The decision aid improved informed decision-making; but has little effect on long-term regular use of aspirin to reduce CRC risk

The pseudogap: friend or foe of high Tc?

Although nineteen years have passed since the discovery of high temperature superconductivity, there is still no consensus on its physical origin. This is in large part because of a lack of understanding of the state of matter out of which the superconductivity arises. In optimally and underdoped materials, this state exhibits a pseudogap at temperatures large compared to the superconducting transition temperature. Although discovered only three years after the pioneering work of Bednorz and Muller, the physical origin of this pseudogap behavior and whether it constitutes a distinct phase of matter is still shrouded in mystery. In the summer of 2004, a band of physicists gathered for five weeks at the Aspen Center for Physics to discuss the pseudogap. In this perspective, we would like to summarize some of the results presented there and discuss its importance in the context of strongly correlated electron systems.Comment: expanded version, 20 pages, 11 figures, to be published, Advances in Physic

Caracterización de pacientes con mielopatía espondilótica cervical intervenidos por disectomía anterior

Introduction: cervical spondylotic myelopathy is a common disease, which accounts for a quarter of all upper-limb paresthesia. Anterior graft discectomy is one of the most widely used surgical techniques in the world to treat this disease.Objective: to characterize patients with cervical spondylotic myelopathy who underwent surgery using the anterior discectomy with graft technique.Methods: a retrospective, descriptive, longitudinal study was conducted in 35 patients with cervical spondylotic myelopathy who underwent surgery using the anterior graft discectomy technique at “Lucia Iñiguez Landín” Clinical Surgical Teaching Hospital from January 2017 to December 2019. The variables studied were: age, sex, race, personal pathological history, signs and symptoms (before the surgery), cervical level affected, sequelae and complications.Results: male patients predominated (59,9 %), with ages between 45 and 60 years (45,71 %) and with personal pathological history of obesity (40 %). The prevailing clinical manifestations before surgery were hyperreflexia (65,71 %) and paresthesia (62,85 %). The most affected cervical segment was C5-C7 (91,42 %). The main complications were generalized hyperreflexia (17,14 %) and pain (8,57 %).Conclusions: patients with cervical spondylotic myelopathy surgically treated by the anterior discectomy with graft technique were mostly male, in ages after the fourth decade of life. Patients presented hyperreflexia before the surgery, and could develop generalized hyperreflexia as a complication.Introducción: la mielopatía espondilótica cervical es una enfermedad frecuente, que representa la cuarta parte de las parestesias en miembros superiores.  La disectomía anterior con injerto es una de las técnicas quirúrgicas más utilizadas en el mundo para tratar esta enfermedad.Objetivo: Caracterizar los pacientes con mielopatía espondilótica cervical intervenidos quirúrgicamente por la técnica disectomía anterior con injerto.Método: Se realizó un estudio observacional, descriptivo, longitudinal retrospectivo en 35 pacientes con mielopatía espondilótica cervical intervenidos quirúrgicamente por la técnica de disectomía anterior con injerto en el Hospital Clínico Quirúrgico Docente “Lucia Iñiguez Landín” en el período de enero del 2017 a diciembre del 2019. Las variables estudiadas fueron: edad, sexo, color de piel, antecedentes patológicos personales, signos y síntomas (antes de la operación), nivel cervical afectado, secuelas y complicaciones.Resultados: Se encontró predominio de pacientes masculinos (59,9 %), con edades entre 45 y 60 años (45,71 %) y con antecedentes patológicos personales de obesidad (40 %). Las manifestaciones clínicas que predominaron antes de la intervención quirúrgica fueron la hiperreflexia (65,71 %) y la parestesia (62,85 %). El segmento cervical más afectado fue C5-C7 (91,42 %). Las principales complicaciones fueron la hiperreflexia generalizada (17,14 %) y el dolor (8,57).Conclusiones: los pacientes con mielopatía espondilótica cervical intervenidos quirúrgicamente por la técnica disectomía anterior con injerto fueron de sexo masculino en su mayoría, con edades pasadas de la cuarta década de vida. Los pacientes presentaron hiperreflexia antes de la operación, pudiendo desarrollar hiperreflexia generalizada como complicación

Primary Role of Functional Ischemia, Quantitative Evidence for the Two-Hit Mechanism, and Phosphodiesterase-5 Inhibitor Therapy in Mouse Muscular Dystrophy

Background. Duchenne Muscular Dystrophy (DMD) is characterized by increased muscle damage and an abnormal blood flow after muscle contraction: the state of functional ischemia. Until now, however, the cause-effect relationship between the pathogenesis of DMD and functional ischemia was unclear. We examined (i) whether functional ischemia is necessary to cause contraction-induced myofiber damage and (ii) whether functional ischemia alone is sufficient to induce the damage. Methodology/Principal Findings. In vivo microscopy was used to document assays developed to measure intramuscular red blood cell flux, to quantify the amount of vasodilatory molecules produced from myofibers, and to determine the extent of myofiber damage. Reversal of functional ischemia via pharmacological manipulation prevented contraction-induced myofiber damage in mdx mice, the murine equivalent of DMD. This result indicates that functional ischemia is required for, and thus an essential cause of, muscle damage in mdx mice. Next, to determine whether functional ischemia alone is enough to explain the disease, the extent of ischemia and the amount of myofiber damage were compared both in control and mdx mice. In control mice, functional ischemia alone was found insufficient to cause a similar degree of myofiber damage observed in mdx mice. Additional mechanisms are likely contributing to cause more severe myofiber damage in mdx mice, suggestive of the existence of a ‘‘two-hit’ ’ mechanism in the pathogenesis of this disease. Conclusions/Significance. Evidence was provided supporting the essential role of functional ischemia in contraction-induced myofiber damage in mdx mice. Furthermore, the first quantitative evidence for the ‘‘two-hit’ ’ mechanism in this disease was documented. Significantly, the vasoactive dru

Non-genetic expression of adolescent idiopathic scoliosis: a case report and review of the literature

Treating children with idiopathic scoliosis can amaze someone at the many different ways in which the deformity can present. Most authors state that genetics stipulates the course of adolescent idiopathic scoliosis. This is mainly based on the high concordance in monozygotic twins. However, there is indication that environmental factors have influences on adolescent idiopathic scoliosis. This is the first report in which a monozygotic twin pair is described concordant for idiopathic scoliosis but with different apical levels, magnitudes and age at detection of scoliosis which stresses the importance of environmental factors

Higher pre-infection vitamin E levels are associated with higher mortality in HIV-1-infected Kenyan women: a prospective study

Background: Low vitamin E levels are often found in HIV-1 infection, and studies have suggested that higher levels may decrease the risk of disease progression. However, vitamin E supplementation has also been reported to increase CCR5 expression, which could increase HIV- 1 replication. We hypothesized that vitamin E levels at HIV-1 acquisition may influence disease progression. Methods: Vitamin E status was measured in stored samples from the last pre-infection visit for 67 Kenyan women with reliably estimated dates of HIV-1 acquisition. Regression analyses were used to estimate associations between pre-infection vitamin E and plasma viral load, time to CD4 count less than 200 cells/[micro]L, and mortality. Results: After controlling for potential confounding factors, each 1 mg/L increase in pre-infection vitamin E was associated with 0.08 log[sub]10 copies/mL (95% CI -0.01 to +0.17) higher set point viral load and 1.58-fold higher risk of mortality (95% CI 1.15�2.16). The association between higher preinfection vitamin E and mortality persisted after adjustment for set point viral load (HR 1.55, 95% CI 1.13�2.13). Conclusion: Higher pre-infection vitamin E levels were associated with increased mortality. Further research is needed to elucidate the role vitamin E plays in HIV-1 pathogenesis.This research was supported by National Institutes of Health grants AI-43844 and AI-38518 (all authors), and Fogarty International Center grant D43 TW000007 (SMG)

A Long Baseline Neutrino Oscillation Experiment Using J-PARC Neutrino Beam and Hyper-Kamiokande

Document submitted to 18th J-PARC PAC meeting in May 2014. 50 pages, 41 figuresDocument submitted to 18th J-PARC PAC meeting in May 2014. 50 pages, 41 figuresDocument submitted to 18th J-PARC PAC meeting in May 2014. 50 pages, 41 figuresHyper-Kamiokande will be a next generation underground water Cherenkov detector with a total (fiducial) mass of 0.99 (0.56) million metric tons, approximately 20 (25) times larger than that of Super-Kamiokande. One of the main goals of Hyper-Kamiokande is the study of $CP$ asymmetry in the lepton sector using accelerator neutrino and anti-neutrino beams. In this document, the physics potential of a long baseline neutrino experiment using the Hyper-Kamiokande detector and a neutrino beam from the J-PARC proton synchrotron is presented. The analysis has been updated from the previous Letter of Intent [K. Abe et al., arXiv:1109.3262 [hep-ex]], based on the experience gained from the ongoing T2K experiment. With a total exposure of 7.5 MW $\times$ 10$^7$ sec integrated proton beam power (corresponding to $1.56\times10^{22}$ protons on target with a 30 GeV proton beam) to a $2.5$-degree off-axis neutrino beam produced by the J-PARC proton synchrotron, it is expected that the $CP$ phase $\delta_{CP}$ can be determined to better than 19 degrees for all possible values of $\delta_{CP}$, and $CP$ violation can be established with a statistical significance of more than $3\,\sigma$ ($5\,\sigma$) for $76$ ($58$) of the $\delta_{CP}$ parameter space

The burden of varicella from a parent's perspective and its societal impact in The Netherlands: an Internet survey

<p>Abstract</p> <p>Background</p> <p>Varicella is a common childhood disease. Only 5% of first varicella-zoster-virus infections occur asymptomatically. Most data on the burden of varicella stem from health service databases. This study aims to provide insight in the burden of varicella from a parent's perspective including cases outside the healthcare system.</p> <p>Methods</p> <p>An internet questionnaire was developed for parents in the Netherlands to report health care resource use and productivity losses during the varicella episode in their child younger than 6 years. 11,367 invitations were sent out to members with children of an internet panel of a market research agency. 4,168 (37%) parents started the questionnaire (response rate), of which 360 (9%) stopped before completion and 1,838 (44%) were out of the target group. In total 1,970 parents completed the questionnaire. The questionnaire provided a symptom list ranging from common symptoms, such as skin vesicles, itching to fits or convulsions. A posteriori, in the analyses, the symptoms 'skin infections', 'fits/convulsions', 'unconsciousness', and 'balance and movement disorders' were labelled as complications. There was no restriction to time since the varicella episode for inclusion in the analyses.</p> <p>Results</p> <p>The 1,970 respondents had in total 2,899 children aged younger than six years, of which 2,564 (88%) children had had varicella. In 62% of the episodes the parent did not seek medical help. In 18% of all episodes symptoms labelled as complications were reported; in 11% of all episodes parents visited a medical doctor (MD) for a complication. Reporting of complications did not differ (X²; p = 0.964) between children with a recent (≤ 12 months ago) or a more distant (> 12 months) history of varicella. Prescription drugs were used in 12% of the children with varicella; OTC drugs in 72%. Parents reported work loss in 17% of the varicella-episodes (23% when MD visit; 14% when no MD-visit) for on average 14 hours, which equals to 2.5 hours of work loss for any given varicella-episode.</p> <p>Conclusions</p> <p>This study shows the full spectrum of varicella-episodes and associated healthcare use, including the large proportion of cases not seeking medical care and the societal impact associated with those cases.</p

A search for the decay modes B+/- to h+/- tau l

We present a search for the lepton flavor violating decay modes B+/- to h+/- tau l (h= K,pi; l= e,mu) using the BaBar data sample, which corresponds to 472 million BBbar pairs. The search uses events where one B meson is fully reconstructed in one of several hadronic final states. Using the momenta of the reconstructed B, h, and l candidates, we are able to fully determine the tau four-momentum. The resulting tau candidate mass is our main discriminant against combinatorial background. We see no evidence for B+/- to h+/- tau l decays and set a 90% confidence level upper limit on each branching fraction at the level of a few times 10^-5.Comment: 15 pages, 7 figures, submitted to Phys. Rev.