fMRI mapping of the visual system in the mouse brain with interleaved snapshot GE-EPI

The use of functional magnetic resonance imaging (fMRI) in mice is increasingly prevalent, providing a means to non-invasively characterise functional abnormalities associated with genetic models of human diseases. The predominant stimulus used in task-based fMRI in the mouse is electrical stimulation of the paw. Task-based fMRI in mice using visual stimuli remains underexplored, despite visual stimuli being common in human fMRI studies. In this study, we map the mouse brain visual system with BOLD measurements at 9.4T using flashing light stimuli with medetomidine anaesthesia. BOLD responses were observed in the lateral geniculate nucleus, the superior colliculus and the primary visual area of the cortex, and were modulated by the flashing frequency, diffuse vs focussed light and stimulus context. Negative BOLD responses were measured in the visual cortex at 10Hz flashing frequency; but turned positive below 5Hz. In addition, the use of interleaved snapshot GE-EPI improved fMRI image quality without diminishing the temporal contrast-noise-ratio. Taken together, this work demonstrates a novel methodological protocol in which the mouse brain visual system can be non-invasively investigated using BOLD fMRI

Systematic review and meta-analysis of the diagnostic accuracy of ultrasonography for deep vein thrombosis

Background Ultrasound (US) has largely replaced contrast venography as the definitive diagnostic test for deep vein thrombosis (DVT). We aimed to derive a definitive estimate of the diagnostic accuracy of US for clinically suspected DVT and identify study-level factors that might predict accuracy. Methods We undertook a systematic review, meta-analysis and meta-regression of diagnostic cohort studies that compared US to contrast venography in patients with suspected DVT. We searched Medline, EMBASE, CINAHL, Web of Science, Cochrane Database of Systematic Reviews, Cochrane Controlled Trials Register, Database of Reviews of Effectiveness, the ACP Journal Club, and citation lists (1966 to April 2004). Random effects meta-analysis was used to derive pooled estimates of sensitivity and specificity. Random effects meta-regression was used to identify study-level covariates that predicted diagnostic performance. Results We identified 100 cohorts comparing US to venography in patients with suspected DVT. Overall sensitivity for proximal DVT (95% confidence interval) was 94.2% (93.2 to 95.0), for distal DVT was 63.5% (59.8 to 67.0), and specificity was 93.8% (93.1 to 94.4). Duplex US had pooled sensitivity of 96.5% (95.1 to 97.6) for proximal DVT, 71.2% (64.6 to 77.2) for distal DVT and specificity of 94.0% (92.8 to 95.1). Triplex US had pooled sensitivity of 96.4% (94.4 to 97.1%) for proximal DVT, 75.2% (67.7 to 81.6) for distal DVT and specificity of 94.3% (92.5 to 95.8). Compression US alone had pooled sensitivity of 93.8 % (92.0 to 95.3%) for proximal DVT, 56.8% (49.0 to 66.4) for distal DVT and specificity of 97.8% (97.0 to 98.4). Sensitivity was higher in more recently published studies and in cohorts with higher prevalence of DVT and more proximal DVT, and was lower in cohorts that reported interpretation by a radiologist. Specificity was higher in cohorts that excluded patients with previous DVT. No studies were identified that compared repeat US to venography in all patients. Repeat US appears to have a positive yield of 1.3%, with 89% of these being confirmed by venography. Conclusion Combined colour-doppler US techniques have optimal sensitivity, while compression US has optimal specificity for DVT. However, all estimates are subject to substantial unexplained heterogeneity. The role of repeat scanning is very uncertain and based upon limited data

Systematic review and meta-analysis of reduction in all-cause mortality from walking and cycling and shape of dose response relationship

BACKGROUND AND OBJECTIVE: Walking and cycling have shown beneficial effects on population risk of all-cause mortality (ACM). This paper aims to review the evidence and quantify these effects, adjusted for other physical activity (PA). DATA SOURCES: We conducted a systematic review to identify relevant studies. Searches were conducted in November 2013 using the following health databases of publications: Embase (OvidSP); Medline (OvidSP); Web of Knowledge; CINAHL; SCOPUS; SPORTDiscus. We also searched reference lists of relevant texts and reviews. STUDY ELIGIBILITY CRITERIA AND PARTICIPANTS: Eligible studies were prospective cohort design and reporting walking or cycling exposure and mortality as an outcome. Only cohorts of individuals healthy at baseline were considered eligible. STUDY APPRAISAL AND SYNTHESIS METHODS: Extracted data included study population and location, sample size, population characteristics (age and sex), follow-up in years, walking or cycling exposure, mortality outcome, and adjustment for other co-variables. We used random-effects meta-analyses to investigate the beneficial effects of regular walking and cycling. RESULTS: Walking (18 results from 14 studies) and cycling (8 results from 7 studies) were shown to reduce the risk of all-cause mortality, adjusted for other PA. For a standardised dose of 11.25 MET.hours per week (or 675 MET.minutes per week), the reduction in risk for ACM was 11% (95% CI = 4 to 17%) for walking and 10% (95% CI = 6 to 13%) for cycling. The estimates for walking are based on 280,000 participants and 2.6 million person-years and for cycling they are based on 187,000 individuals and 2.1 million person-years. The shape of the dose-response relationship was modelled through meta-analysis of pooled relative risks within three exposure intervals. The dose-response analysis showed that walking or cycling had the greatest effect on risk for ACM in the first (lowest) exposure interval. CONCLUSIONS AND IMPLICATIONS: The analysis shows that walking and cycling have population-level health benefits even after adjustment for other PA. Public health approaches would have the biggest impact if they are able to increase walking and cycling levels in the groups that have the lowest levels of these activities. REVIEW REGISTRATION: The review protocol was registered with PROSPERO (International database of prospectively registered systematic reviews in health and social care) PROSPERO 2013: CRD42013004266

Insights from a national survey into why substance abuse treatment units add prevention and outreach services

BACKGROUND: Previous studies have found that even limited prevention-related interventions can affect health behaviors such as substance use and risky sex. Substance abuse treatment providers are ideal candidates to provide these services, but typically have little or no financial incentive to do so. The purpose of this study was therefore to explore why some substance abuse treatment units have added new prevention and outreach services. Based on an ecological framework of organizational strategy, three categories of predictors were tested: (1) environmental, (2) unit-level, and (3) unit leadership. RESULTS: A lagged cross-sectional logistic model of 450 outpatient substance abuse treatment units revealed that local per capita income, mental health center affiliation, and clinical supervisors' graduate degrees were positively associated with likelihood of adding prevention-related education and outreach services. Managed care contracts and methadone treatment were negatively associated with addition of these services. No hospital-affiliated agencies added prevention and outreach services during the study period. CONCLUSION: Findings supported the study's ecological perspective on organizational strategy, with factors at environmental, unit, and unit leadership levels associated with additions of prevention and outreach services. Among the significant predictors, ties to managed care payers and unit leadership graduate education emerge as potential leverage points for public policy. In the current sample, units with managed care contracts were less likely to add prevention and outreach services. This is not surprising, given managed care's emphasis on cost control. However, the association with this payment source suggests that public managed care programs might affects prevention and outreach differently through revised incentives. Specifically, government payers could explicitly compensate substance abuse treatment units in managed care contracts for prevention and outreach. The effects of supervisor graduate education on likelihood of adding new prevention and outreach programs suggests that leaders' education can affect organizational strategy. Foundation and government officials may encourage prevention and outreach by funding curricular enhancements to graduate degree programs demonstrating the importance of public goods. Overall, these findings suggest that both money and professional education affect substance abuse treatment unit additions of prevention and outreach services, as well as other factors less amenable to policy intervention

Mindfulness-Based Cognitive Therapy (MBCT) For Health Anxiety (Hypochondriasis): Rationale, Implementation and Case Illustration.

Recent research has shown that mindfulness-based cognitive therapy (MBCT) could be a useful alternative approach to the treatment of health anxiety and deserves further investigation. In this paper, we outline the rationale for using MBCT in the treatment of this condition, namely its hypothesised impact on the underlying mechanisms which maintain health anxiety, such as rumination and avoidance, hypervigilance to body sensations and misinterpretation of such sensations. We also describe some of the adaptations which were made to the MBCT protocol for recurrent depression in this trial and discuss the rationale for these adaptations. We use a case example from the trial to illustrate how MBCT was implemented and outline the experience of one of the participants who took part in an 8-week MBCT course. Finally, we detail some of the more general experiences of participants and discuss the advantages and possible limitations of this approach for this population, as well as considering what might be useful avenues to explore in future research

A primary care, multi-disciplinary disease management program for opioid-treated patients with chronic non-cancer pain and a high burden of psychiatric comorbidity

BACKGROUND: Chronic non-cancer pain is a common problem that is often accompanied by psychiatric comorbidity and disability. The effectiveness of a multi-disciplinary pain management program was tested in a 3 month before and after trial. METHODS: Providers in an academic general medicine clinic referred patients with chronic non-cancer pain for participation in a program that combined the skills of internists, clinical pharmacists, and a psychiatrist. Patients were either receiving opioids or being considered for opioid therapy. The intervention consisted of structured clinical assessments, monthly follow-up, pain contracts, medication titration, and psychiatric consultation. Pain, mood, and function were assessed at baseline and 3 months using the Brief Pain Inventory (BPI), the Center for Epidemiological Studies-Depression Scale scale (CESD) and the Pain Disability Index (PDI). Patients were monitored for substance misuse. RESULTS: Eighty-five patients were enrolled. Mean age was 51 years, 60% were male, 78% were Caucasian, and 93% were receiving opioids. Baseline average pain was 6.5 on an 11 point scale. The average CESD score was 24.0, and the mean PDI score was 47.0. Sixty-three patients (73%) completed 3 month follow-up. Fifteen withdrew from the program after identification of substance misuse. Among those completing 3 month follow-up, the average pain score improved to 5.5 (p = 0.003). The mean PDI score improved to 39.3 (p < 0.001). Mean CESD score was reduced to 18.0 (p < 0.001), and the proportion of depressed patients fell from 79% to 54% (p = 0.003). Substance misuse was identified in 27 patients (32%). CONCLUSIONS: A primary care disease management program improved pain, depression, and disability scores over three months in a cohort of opioid-treated patients with chronic non-cancer pain. Substance misuse and depression were common, and many patients who had substance misuse identified left the program when they were no longer prescribed opioids. Effective care of patients with chronic pain should include rigorous assessment and treatment of these comorbid disorders and intensive efforts to insure follow up

Incidence and Risk of QTc Interval Prolongation among Cancer Patients Treated with Vandetanib: A Systematic Review and Meta-analysis

Vandetanib is a multikinase inhibitor that is under assessment for the treatment of various cancers. QTc interval prolongation is one of the major adverse effects of this drug, but the reported incidence varies substantially among clinical trials. We performed a systematic review and meta-analysis to obtain a better understanding in the risk of QTc interval prolongation among cancer patients administered vandetanib.Eligible studies were phase II and III prospective clinical trials that involved cancer patients who were prescribed vandetanib 300 mg/d and that included data on QTc interval prolongation. The overall incidence and risk of QTc interval prolongation were calculated using random-effects or fixed-effects models, depending on the heterogeneity of the included studies. Nine trials with 2,188 patients were included for the meta-analysis. The overall incidence of all-grade and high-grade QTc interval prolongation was 16.4% (95% CI, 8.1-30.4%) and 3.7% (8.1-30.4%), respectively, among non-thyroid cancer patients, and 18.0% (10.7-28.6%) and 12.0% (4.5-28.0%), respectively, among thyroid cancer patients. Patients with thyroid cancer who had longer treatment duration also had a higher incidence of high-grade events, with a relative risk of 3.24 (1.57-6.71), than patients who had non-thyroid cancer. Vandetanib was associated with a significantly increased risk of all-grade QTc interval prolongation with overall Peto odds ratios of 7.26 (4.36-12.09) and 5.70 (3.09-10.53) among patients with non-thyroid cancer and thyroid cancer, respectively, compared to the controls.Treatment with vandetanib is associated with a significant increase in the overall incidence and risk of QTc interval prolongation. Different cancer types and treatment durations may affect the risk of developing high-grade QTc interval prolongation