Single-Dose Psilocybin Treatment for Major Depressive Disorder: A Randomized Clinical Trial.

Importance: Psilocybin shows promise as a treatment for major depressive disorder (MDD). Objective: To evaluate the magnitude, timing, and durability of antidepressant effects and safety of a single dose of psilocybin in patients with MDD. Design, Setting, and Participants: In this phase 2 trial conducted between December 2019 and June 2022 at 11 research sites in the US, participants were randomized in a 1:1 ratio to receive a single dose of psilocybin vs niacin placebo administered with psychological support. Participants were adults aged 21 to 65 years with a Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition diagnosis of MDD of at least 60 days' duration and moderate or greater symptom severity. Exclusion criteria included history of psychosis or mania, active substance use disorder, and active suicidal ideation with intent. Participants taking psychotropic agents who otherwise met inclusion/exclusion criteria were eligible following medication taper. Primary and secondary outcomes and adverse events (AEs) were assessed at baseline (conducted within 7 days before dosing) and at 2, 8, 15, 29, and 43 days after dosing. Interventions: Interventions were a 25-mg dose of synthetic psilocybin or a 100-mg dose of niacin in identical-appearing capsules, each administered with psychological support. Main Outcomes and Measures: The primary outcome was change in central rater-assessed Montgomery-Asberg Depression Rating Scale (MADRS) score (range, 0-60; higher scores indicate more severe depression) from baseline to day 43. The key secondary outcome measure was change in MADRS score from baseline to day 8. Other secondary outcomes were change in Sheehan Disability Scale score from baseline to day 43 and MADRS-defined sustained response and remission. Participants, study site personnel, study sponsor, outcome assessors (raters), and statisticians were blinded to treatment assignment. Results: A total of 104 participants (mean [SD] age, 41.1 [11.3] years; 52 [50%] women) were randomized (51 to the psilocybin group and 53 to the niacin group). Psilocybin treatment was associated with significantly reduced MADRS scores compared with niacin from baseline to day 43 (mean difference,-12.3 [95% CI, -17.5 to -7.2]; P <.001) and from baseline to day 8 (mean difference, -12.0 [95% CI, -16.6 to -7.4]; P < .001). Psilocybin treatment was also associated with significantly reduced Sheehan Disability Scale scores compared with niacin (mean difference, -2.31 [95% CI, 3.50-1.11]; P < .001) from baseline to day 43. More participants receiving psilocybin had sustained response (but not remission) than those receiving niacin. There were no serious treatment-emergent AEs; however, psilocybin treatment was associated with a higher rate of overall AEs and a higher rate of severe AEs. Conclusions and Relevance: Psilocybin treatment was associated with a clinically significant sustained reduction in depressive symptoms and functional disability, without serious adverse events. These findings add to increasing evidence that psilocybin-when administered with psychological support-may hold promise as a novel intervention for MDD. Trial Registration: ClinicalTrials.gov Identifier: NCT03866174.

Healthcare Professional Preferences for Prescribing Artemisinins and Quinine for Malaria in Burundi.

BACKGROUND: Malaria is a significant cause of morbidity and mortality throughout the world and particularly sub-Saharan Africa. The World Health Organization and many national bodies, including Burundi, recommend artemisinin-based therapy as first-line treatment for uncomplicated and severe malaria. Implementing this recommendation requires healthcare professionals' acceptance of this treatment as the optimal choice. METHODS: A survey was conducted among Burundian healthcare professionals from June to September 2017 to assess prescribing preferences regarding artemisinins versus quinine for treating malaria. Healthcare professionals were surveyed from 32 health facilities in 10 provinces. Respondents included both physicians and nurses who provided responses about their antimalarial treatment preferences for a variety of clinical scenarios. Comparisons among healthcare professionals, their level of training, work setting, and length of work experience were examined using a series of stratified analyses, where the Pearson Chi-square statistic and odds ratios with 95% confidence intervals were calculated. RESULTS: Respondents included 101 doctors and 196 nurses. Seventy-nine percent of respondents worked in hospitals, while 58% had more than 5 years of work experience. Although 94% of respondents correctly identified artemisinin-based treatment as first-line therapy according to the national protocol, 24-40% of respondents preferred the use of quinine in various hypothetical clinical scenarios. Overall, nurses were at greater odds of preferring quinine versus artemisinins compared with physicians. Availability of artemisinins was associated positively with artemisinin preference. These results did not vary by duration of work experience. CONCLUSIONS: Though knowledge of artemisinin-based therapy was recognised by the majority of respondents as the recommended antimalarial treatment, a high proportion of Burundian healthcare professionals, especially nurses, prefer using oral and IV quinine in a number of clinical scenarios. These findings identify a significant barrier to the satisfactory implementation of a life-saving treatment in accordance with national and international recommendations.

In-Orbit Performance of the GRACE Follow-on Laser Ranging Interferometer.

The Laser Ranging Interferometer (LRI) instrument on the Gravity Recovery and Climate Experiment (GRACE) Follow-On mission has provided the first laser interferometric range measurements between remote spacecraft, separated by approximately 220 km. Autonomous controls that lock the laser frequency to a cavity reference and establish the 5 degrees of freedom two-way laser link between remote spacecraft succeeded on the first attempt. Active beam pointing based on differential wave front sensing compensates spacecraft attitude fluctuations. The LRI has operated continuously without breaks in phase tracking for more than 50 days, and has shown biased range measurements similar to the primary ranging instrument based on microwaves, but with much less noise at a level of 1 nm/sqrt[Hz] at Fourier frequencies above 100 mHz.

Oiling the gate: a mobile application to improve the admissions process from the emergency department to an academic community hospital inpatient medicine service.

The process of admitting patients from the emergency department (ED) to an academic internal medicine (AIM) service in a community teaching hospital is one fraught with variability and disorder. This results in an inconsistent volume of patients admitted to academic versus private hospitalist services and results in frustration of both ED and AIM clinicians. We postulated that implementation of a mobile application (app) would improve provider satisfaction and increase admissions to the academic service. The app was designed and implemented to be easily accessible to ED physicians, regularly updated by academic residents on call, and a real-time source of the number of open AIM admission spots. We found a significant improvement in ED and AIM provider satisfaction with the admission process. There was also a significant increase in admissions to the AIM service after implementation of the app. We submit that the implementation of a mobile app is a viable, cost-efficient, and effective method to streamline the admission process from the ED to AIM services at community-based hospitals.

Effect of Evolocumab on Lipoprotein Particles.

The level of low-density lipoprotein cholesterol (LDL-C) reflects the cholesterol carried mainly by low-density lipoprotein particles (LDL-P). LDL-C, however, does not always correlate with LDL-P because of the variable amounts of cholesterol per particle. Consideration of LDL-P concentrations in addition to LDL-C may help guide therapeutic decisions in a select number of patients. Evolocumab is a fully human monoclonal antibody directed against proprotein convertase subtilisin-kexin type 9 that lowers both LDL-C and cardiovascular events. To evaluate the effect of evolocumab on serum levels and size of lipoprotein particles, we conducted a post hoc subanalysis of 619 patients from the Durable Effect of PCSK9 Antibody Compared with Placebo Study or DESCARTES trial, a 52-week, randomized, double-blind, placebo-controlled, global study of patients with hyperlipidemia. At baseline, mean LDL-P concentration was 1077 nmol/L for the placebo group and 1100 nmol/L for the evolocumab group. In patients receiving evolocumab, week 52 total LDL-P concentration decreased to 610 nmol/L, a treatment difference of 50% versus placebo. Evolocumab also reduced concentrations of medium very low-density lipoprotein particles (VLDL-P), small VLDL-P, and intermediate-density lipoprotein particle: median (Q1, Q3) changes were -15.2% (-48, 48), -29% (-54, 18), and -36% (-70, 22), respectively. Mean (95% confidence interval) % changes in total LDL particle size in the evolocumab group was -1.7 (-2.0, -1.4); % changes in HDL and VLDL particle sizes were 1.1 (0.7, 1.5) and 8.7 (7.0, 10.5), respectively. Changes in total LDL, HDL, and VLDL particle sizes (vs placebo) were all significant (p <0.001). In conclusion, evolocumab significantly lowers atherogenic lipoprotein particles including low-density and remnant lipoproteins.

Listening through the learning conversation: a thought provoking intervention.

This article was migrated. The article was marked as recommended. Feedback plays an essential role in the learning that occurs on life support courses. Since 2007 the preferred method of managing feedback has been the learning conversation, but it remains an area that many facilitators profess to finding challenging. In this article we will explore how simple conversational techniques involved in active listening can lead to significant learning.

Scalp Condition Impacts Hair Growth and Retention via Oxidative Stress.

Conventionally, the medical focus has been either on hair loss or the condition of the scalp in terms of specific dermatological diseases. Indeed, the proximate structural arrangement of the scalp and hair leads to an interdependent relationship between the two. While protective benefits of the hair to the scalp are obvious, the role of the scalp as an incubatory environment for the preemergent hair fiber has largely been ignored. In fact, there is a wealth of observational data on specific dermatological conditions of the scalp providing evidence for the role of the scalp condition in supporting the production of healthy hair. Oxidative stress, the inability of the body to sufficiently counteract the sources of oxidation, is prevalent in many skin conditions, including normal skin aging. On the scalp, the hair appears to be impacted prior to emergence, and oxidative stress appears to play a role in premature hair loss. The scalp commensal organism, Malassezia, has been recognized to be a source of oxidative damage. Therefore, hair care products, specifically shampoos, with active Malassezia inhibitory agents, such as zinc pyrithione, tend to reduce premature hair loss, besides the known benefits in treating specific dermatologic scalp pathologies, and therefore should represent an integral part of every treatment regimen for hair loss, even in individuals not showing symptoms of scalp pathologies.

Automated Detection of Privacy Sensitive Conditions in C-CDAs: Security Labeling Services at the Department of Veterans Affairs.

Care coordination across healthcare organizations depends upon health information exchange. Various policies and laws govern permissible exchange, particularly when the information includes privacy sensitive conditions. The Department of Veterans Affairs (VA) privacy policy has required either blanket consent or manual sensitivity review prior to exchanging any health information. The VA experience has been an expensive, administratively demanding burden on staffand Veterans alike, particularly for patients without privacy sensitive conditions. Until recently, automatic sensitivity determination has not been feasible. This paper proposes a policy-driven algorithmic approach (Security Labeling Service or SLS) to health information exchange that automatically detects the presence or absence of specific privacy sensitive conditions and then, to only require a Veteran signed consent for release when actually present. The SLS was applied successfully to a sample of real patient Consolidated-Clinical Document Architecture(C-CDA) documents. The SLS identified standard terminology codes by both parsing structured entries and analyzing textual information using Natural Language Processing (NLP).

Improved functional properties of glycosylated soy protein isolate using D-glucose and xanthan gum.

Functional properties of the soy protein need to improve to have better applications in food industry. Alkali extracted and acid precipitated soy protein isolate (SPI) was glycosylated using D-glucose (G) and Xanthan gum (X) via Maillard reaction to improve solubility. The effects of SPI to G and SPI to X ratios (SPI:G = 2:1, 1:1, and 1:2; SPI:X = 100:1 and 10:1) and incubation time (0, 6, 12, and 24 h) on the solubility and functional properties of glycosylated SPI were evaluated. The SPI:G ratio of 1:2 yielded a maximum degree of glycosylation of 71.1 %. The solubility of SPI after glycosylation significantly increased (P < 0.05) at pH 4.0-8.0 compared to SPI alone. Although the emulsion stability of glycosylated SPIs has not significantly increased (P > 0.05), the emulsifying activity improved significantly (P < 0.05). Glycosylation with SPI-X at a ratio of 10: 1 showed maximum emulsifying activity of 191.6 m(2)/g (SPI alone: 66.3 m(2)/g). Moreover, the SPI:X (ratio of 100:1) showed the maximum foaming activity (205 mL) compared to SPI alone (155 mL). The foaming stability of SPI (2.6 %) increased to 5.5 and 8.2 % when using xanthan gum at the ratio of 100:1 and 10:1, respectively. Glycosylated SPI with enhanced emulsifying and foaming properties has potential to improve the functional quality of the food products.

Reflecting reality: pager simulations in undergraduate education.

BACKGROUND: Fifth-year medical students build on their experiences of simulation and clinical placement to undertake a period of pager contact, during which they must respond appropriately to a variety of 'bleep' messages, culminating in the team management of a complex scenario. CONTEXT: In anticipation of their graduation to foundation-year doctors, fifth-year students in their final term on clinical placement at Lancashire Teaching Hospitals experience a period of time on call, when they receive a series of pager messages that they must manage whilst on clinical placement. They are expected to manage the variety of random events as if they were doctors on call. INNOVATION: With the agreement of all affected parties, students experience some simulated events of the type that they may experience while on call as foundation-year doctors. They are required to respond appropriately to these and are offered feedback on performance after they gather for a cardiac arrest simulation. DISCUSSION: This has been a very popular and impactful experience for final-term undergraduates as they anticipate the challenges of becoming foundation-year doctors. The need for effective management of clinical and non-technical skills presented in an ill-defined problem space is an appropriate challenge that serves to reassure them about their capacity to manage the unexpected. [The students] are expected to manage the variety of random events as if they were doctors on call.

Policy Management Standards Enabling Trustworthy pHealth.

Current paradigm changes for improving safety, quality and efficiency of care processes under massive deployment of information and communication technologies (ICT) place high requirements on privacy and security. These mainly focus on privilege management and access control harmonized in international standards and their further evolution. NIST and ISO, but especially HL7 play a prominent role in this context. Starting with classic role-based access control (RBAC) foundations to new specifications for security and privacy labeling of segmented health information, HL7 security is presented as a scalable intermediate solution on the way to comprehensive privilege management and access control by explicit, ontology-based, formal and therefore machine-processable policies. The successfully balloted HL7 labeling specification supports context-sensitive communication and cooperation between different stakeholders and processes with different purposes of use, based on meta-data of information, actors and processes involved. Basics of policy management and practical solutions are discussed.

Phenolics and antioxidant activity of Saskatoon berry (Amelanchier alnifolia) pomace extract.

Saskatoon berries (Amelanchier alnifolia Nutt.) have significantly higher levels of anthocyanins (ACY) among berries with potential health benefits. The pomace is a by-product of juice extracted from berries and is a potential source of inexpensive polyphenols. The objectives of this study were to extract the maximum amount of total phenolics from saskatoon pomace, to determine the antioxidant activity, and to identify individual phenolic components. Pomace extracts showed high content of total phenolics, total ACY, and total flavonoids of 43.3, 2.8, and 10.3 g/kg of dried weight (DW) of pomace. A high oxygen radical absorbing capacity value of 119.4 µmol Trolox equivalents/g DW and free radical scavenging activity of pomace extract (200 ppm, 86.8%) were observed. Five major ACY, two flavonols, and three chlorogenic acids were identified and quantified in pomace extracts. This study shows that saskatoon berries pomace rich in antioxidant phenolics could be extracted by "green" solvents (water and ethanol) and used as suitable food product applications.

Whole-chain traceability, is it possible to trace your hamburger to a particular steer, a U. S. perspective.

Traceability through the entire food supply chain from conception to consumption is a pressing need for the food industry, consumers and government regulators. A robust, whole-chain traceability system is needed that will effectively address food quality, food safety and food defense issues by providing real-time, transparent and reliable information from beef production through slaughter and distribution to the consumer. Traceability is an expanding part of the food safety continuum that minimizes the risk of foodborne diseases, assures quality and cold-chain integrity. Traceability can be a positive competitive marketing edge for beef producers who can verify specific quality attributes such as humane production or grass fed or Certified Organic. In this review we address the benefits as well as the remaining issues for whole-chain traceability in the beef industry, with particular focus on ground beef for the markets in the United States.

Translating standards into practice: experience and lessons learned at the Department of Veterans Affairs.

The increased need for interoperable electronic health records in health care organizations underscores the importance of standards. The US Department of Veterans Affairs (VA) has a long history of developing and adopting various types of health care data standards. The authors present in detail their experience in this domain. A formal organization within VA is responsible for helping to develop and implement standards. This group has produced a Standards Life Cycle (SLC) process endorsed by VA key business and information technology (IT) stakeholders. It coordinates the identification, description, and implementation of standards aligned with VA business requirements. In this paper, we review the adoption of four standards in the categories of security and privacy, terminology, health information exchange, and modeling tools; emphasizing the implementation approach used in each. In our experience, adoption is facilitated by internal staff with expertise in standards development and adoption. Use of processes such as an SLC and tools such as an enterprise requirement repository help formally track and ensure that IT development and acquisition incorporate these standards. An organization should adopt standards that are aligned with its business priorities and favor those that are more readily implementable. To assist with this final point, we offer a standard "Likelihood of Adoption Scale," which changes as standards specifications evolve from PDF documents only, to PDF documents with construction and testing tools, to fully functional reference implementations.

The Department of Veterans Affairs, Department of Defense, and Kaiser Permanente Nationwide Health Information Network exchange in San Diego: patient selection, consent, and identity matching.

The Nationwide Health Information Network allow for the secure exchange of Electronic Health Records over the Internet. The Department of Veterans Affairs, Department of Defense, and Kaiser Permanente, participated in an implementation of the NwHIN specifications in San Diego, California. This paper focuses primarily on patient involvement. Specifically, it describes how the shared patients were identified, were invited to participate and to provide consent for disclosing parts of their medical record, and were matched across organizations. A total 1,144 were identified as shared patients. Invitation letters containing consent forms were mailed and resulted in 42% participation. Invalid consent forms were a significant issue (25%). Initially, the identity matching algorithms yielded low success rate (5%). However, elimination of certain traits and abbreviations and probabilistic algorithms have significantly increased matching rate. Access to information from external sources better informs providers, improves decisions and efficiency, and helps meet the meaningful use criteria.

Development of a method for the determination of glycine in human cerebrospinal fluid using pre-column derivatization and LC-MS/MS.

An LC-MS/MS method using pre-column derivatization with phenylisothiocyanate (PITC) was developed to quantify glycine in human cerebrospinal fluid (CSF) and applied to the determination of glycine in human samples collected during clinical testing. The calibration curve range for the assay was 50-10,000 ng/mL and ¹³C2¹5N-glycine was used as an internal standard. Artificial CSF was used as a surrogate matrix for standards due to the presence of endogenous glycine in human CSF and this approach was validated with additional experiments involving either standard addition, or stable labeled glycine as an alternate calibration standard for endogenous glycine. Interday bias (% RE) and precision (% CV) were -4.2 and 12.3% at the LLOQ, and less than ±0.9 and 8.3% for higher concentrations, respectively. Glycine was stable in artificial CSF for at least 5h at room temperature, 55 days at -70 °C (-60 to -80 °C range), and through three freeze-thaw cycles.