Faculty Bibliography

BACKGROUND: Clinically significant anxiety and depression are common in patients with cancer, and are associated with poor psychiatric and medical outcomes. Historical and recent research suggests a role for psilocybin to treat cancer-related anxiety and depression. METHODS: In this double-blind, placebo-controlled, crossover trial, 29 patients with cancer-related anxiety and depression were randomly assigned and received treatment with single-dose psilocybin (0.3 mg/kg) or niacin, both in conjunction with psychotherapy. The primary outcomes were anxiety and depression assessed between groups prior to the crossover at 7 weeks. RESULTS: Prior to the crossover, psilocybin produced immediate, substantial, and sustained improvements in anxiety and depression and led to decreases in cancer-related demoralization and hopelessness, improved spiritual wellbeing, and increased quality of life. At the 6.5-month follow-up, psilocybin was associated with enduring anxiolytic and anti-depressant effects (approximately 60-80% of participants continued with clinically significant reductions in depression or anxiety), sustained benefits in existential distress and quality of life, as well as improved attitudes towards death. The psilocybin-induced mystical experience mediated the therapeutic effect of psilocybin on anxiety and depression. CONCLUSIONS: In conjunction with psychotherapy, single moderate-dose psilocybin produced rapid, robust and enduring anxiolytic and anti-depressant effects in patients with cancer-related psychological distress. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00957359.

BACKGROUND:Chronic kidney disease (CKD) is common, but the frequency of albuminuria testing and referral to nephrology care has been difficult to measure. We here characterize CKD prevalence and recognition in a complete healthcare utilization cohort of the Stockholm region, in Sweden. METHODS:. We also assessed the performance of diagnostic testing (albuminuria), nephrology consultations, and utilization of ICD-10 diagnoses. RESULTS:A total of 68 894 individuals had CKD, with a crude CKD prevalence of 6.11% [95% confidence interval (CI): 6.07-6.16%] and a prevalence standardized to the European population of 5.38% (5.33-5.42%). CKD was more prevalent among the elderly (28% prevalence >75 years old), women (6.85 versus 5.24% in men), and individuals with diabetes (17%), hypertension (17%) or cardiovascular disease (31%). The frequency of albuminuria monitoring was low, with 38% of diabetics and 27% of CKD individuals undergoing albuminuria testing over 2 years. Twenty-three per cent of the 16 383 individuals satisfying selected KDIGO criteria for nephrology referral visited a nephrologist. Twelve per cent of CKD patients carried an ICD-10 diagnostic code of CKD. CONCLUSIONS:An estimated 6% of the adult Stockholm population accessing healthcare has CKD, but the frequency of albuminuria testing, nephrology consultations and registration of CKD diagnoses was suboptimal despite universal care. Improving provider awareness and treatment of CKD could have a significant public health impact.

Besides amyloid deposition, white matter (WM) changes are involved in the early pathogenesis of Alzheimer's Disease (AD), including inflammation, demyelination and axonal loss. Using simultaneous PET and MRI, we investigated differences in WM microstructural integrity, measured with Diffusion Kurtosis Imaging (DKI), with respect to beta amyloid (Aa) deposition as measured with18F-Florbetapir PET. DKI is a clinically feasible diffusion MRI method that extends beyond Diffusion Tensor Imaging and probes non-Gaussian diffusion properties of nervous tissue, and allows for quantifying the microstructural index for the axonal water fraction (AWF), a specific marker for axonal degeneration and demyelination. Methods: 34 subjects were scanned on a 3T integrated PET-MRI system (Siemens Biograph mMR, VB20). 18FFlorbetapir (9 mCi, Eli Lilly) was injected intravenously and a static 20-minute PET image was reconstructed starting at 40 min post-injection using a UTE-based attenuation map. An anatomical MP-RAGE was acquired for cortical and sub-cortical segmentation using Freesurfer. Hippocampal volume was normalized to the estimated total intracranial volume. The standardized uptake values (SUV) in 5 cortical regions known for pathological uptake of Florbetapir (anterior and posterior cingulate, medial orbito-frontal, parietal and temporal), normalized to the cerebellum, yielded mean cortical relative SUV (SUVr). DKI provided parametric maps for the radial diffusivity (RD), radial kurtosis (RK), and the AWF. Using a lower and higher mean SUVr threshold of 1.0 and 1.1, age- and gender-controlled subjects were categorized into Aa negative (Aa-) (n = 13, 5 females, age = 69.8 +/- 5.1 yrs), Aa intermediate (Aai) (n = 13, 8 females, age = 68.9 +/- 4.8 yrs), or Aa positive (Aa+) (n = 8, 4 females, age = 70.6 +/- 5.3 yrs). Using Tract-Based Spatial Statistics (TBSS), skeletonized voxel-wise analysis was performed to identify areas of differences in the diffusion metrics while covarying for age. Separately, WM regions of interests (ROIs) were automatically segmented using atlas registration over which mean values were extracted. Analysis of covariance covarying for age was used to compare diffusion metrics and hippocampal volume among groups. Results: See figure. Results from both TBSS and ROI analysis demonstrated changes in the fornix and the genu of the corpus callosum. Between the Aa- and Aai groups, RD decreased while RK and AWF increased. Conversely, between the Aai and Aa+ groups, RD increased RD while RK and AWF decreased. A trend towards significantly higher hippocampal volume in the Aai group was observed. Conclusions: We report changes in RD, RK and AWF in opposite directions between Aa- and Aa~, and between Aa~ and Aa+, respectively, suggesting that different mechanisms affect the microstructure during different stages of AD. Early on, mechanisms including microglial activation may restrict diffusion, resulting in the observed decrease in RD and increase in RK and AWF. Later on, neurodegenerative effects such as demyelination and axonal loss may outweigh inflammation, resulting in the observed increase in RD and decrease in RK and AWF. [IMAGE PRESENTED]

The Society for Academic Emergency Medicine (SAEM) consensus conference provided many platforms for patient advocates to share their experiences and demonstrate the powerful contribution they have to offer to the decision-making process. One such platform was the presentation of a film 'The Faces of Medical Error: From Tears to Transparency' shared by Patty and David Skolnik. In this article the Skolniks build on their story shared at the SAEM consensus conference and the panel discussion. They provide further insight drawn from nine years of experiences as advocates for patient safety, including their reflections on working with, training and educating medical professionals, lawmakers, and consumers in shared decision-making and informed consent

For many people the Emergency Department (ED) is the first point of access to healthcare for acute needs, and a recurring location for many with chronic healthcare needs. While the ED is well placed to identify unmet needs it can also be a net that people slip through when faced with uncoordinated and expensive healthcare challenges. Thus the ED has a responsibility to set patients on a safe and meaningful care trajectory which can only be done in consultation and partnership with the patients themselves. The purpose of this article is to present crucial aspects of patient engagement that are essential for future research to foster an environment of co-learning and respect that encourages ongoing involvement by patients, families, and staff

BACKGROUND: Little is known about the optimal use of shared decision making (SDM) to guide palliative and end-of-life decisions in the emergency department (ED). OBJECTIVE: To convene a working group to develop a set of research questions that, when answered, will substantially advance the ability of clinicians to use SDM to guide palliative and end-of-life care decisions in the ED. METHODS: Participants were identified based on expertise in emergency, palliative, or geriatrics care, policy, or patient-advocacy and spanned physician, nursing, social work, legal, and patient perspectives. Input from the group was elicited using a time-staggered Delphi process including three teleconferences, an open platform for asynchronous input, and an in-person meeting to obtain a final round of input from all members and to identify and resolve or describe areas of disagreement. CONCLUSION: Key research questions identified by the group related to which ED patients are likely to benefit from palliative care, what interventions can most effectively promote palliative care in the ED, what outcomes are most appropriate to assess the impact of these interventions, what is the potential for initiating advance care planning in the ED to help patients define long-term goals of care, and what policies influence palliative and end-of-life care decision making in the ED. Answers to these questions have the potential to substantially improve the quality of care for ED patients with advanced illness

Incidental and secondary findings have become an important by-product of diagnostic testing, and their ramifications affect clinical care, research, and policy. Given parallels in the reporting and management of such findings on diagnostic imaging, radiologists may draw from ongoing discussions in medical genetics to rethink more patient-centered approaches to analogous clinical, ethical, and medicolegal dilemmas. Low-risk incidental findings in particular may be drivers of unnecessary testing, invasive procedures, and overtreatment, with associated financial, psychological, and clinical consequences. As radiologists act in patients' best interests by strengthening standardized guidelines on how each finding merits further diagnostic testing or treatment, perhaps the greatest challenge for producing such guidelines is for low-risk incidental findings, for which adverse consequences are unlikely but associated with substantial uncertainty because of the lack of strong evidence on which to base the recommendations. More uniform recommendations for managing low-risk radiologic incidental findings should therefore aim to provide reasonable options that apply across a spectrum of patient preferences. These will require evaluation through research and will ultimately influence the quality of care. Specific areas for exploration may include (1) better gauging of patient attitudes and preferences regarding low-risk incidental findings, (2) using patient preferences to inform more uniform recommendations for low-risk findings that apply across a spectrum of preferences and help guide shared decision making, and (3) when patients endorse a strong preference not to discover low-risk incidental findings, how it might be possible for professional standards to curtail their generation in specific circumstances.

Propensity score methods, such as subclassification, are a common approach to control for confounding when estimating causal effects in non-randomized studies. Propensity score subclassification groups individuals into subclasses based on their propensity score values. Effect estimates are obtained within each subclass and then combined by weighting by the proportion of observations in each subclass. Combining subclass-specific estimates by weighting by the inverse variance is a promising alternative approach; a similar strategy is used in meta-analysis for its efficiency. We use simulation to compare performance of each of the two methods while varying (i) the number of subclasses, (ii) extent of propensity score overlap between the treatment and control groups (i.e., positivity), (iii) incorporation of survey weighting, and (iv) presence of heterogeneous treatment effects across subclasses. Both methods perform well in the absence of positivity violations and with a constant treatment effect with weighting by the inverse variance performing slightly better. Weighting by the proportion in subclass performs better in the presence of heterogeneous treatment effects across subclasses. We apply these methods to an illustrative example estimating the effect of living in a disadvantaged neighborhood on risk of past-year anxiety and depressive disorders among U.S. urban adolescents. This example entails practical positivity violations but no evidence of treatment effect heterogeneity. In this case, weighting by the inverse variance when combining across propensity score subclasses results in more efficient estimates that ultimately change inference. Copyright © 2016 John Wiley & Sons, Ltd.