Synthesis,characterization, and monoamine transporter activity of the new psychoactive substance 3′,4′‐methylenedioxy‐4‐methylaminorex (MDMAR)

The recent occurrence of deaths associated with the psychostimulant cis‐4,4′‐dimethylaminorex (4,4′‐DMAR) in Europe indicated the presence of a newly emerged psychoactive substance on the market. Subsequently, the existence of 3,4‐methylenedioxy‐4‐methylaminorex (MDMAR) has come to the authors' attention and this study describes the synthesis of cis‐ and trans‐MDMAR followed by extensive characterization by chromatographic, spectroscopic, mass spectrometric platforms and crystal structure analysis. MDMAR obtained from an online vendor was subsequently identified as predominantly the cis‐isomer (90%). Exposure of the cis‐isomer to the mobile phase conditions (acetonitrile/water 1:1 with 0.1% formic acid) employed for high performance liquid chromatography analysis showed an artificially induced conversion to the trans‐isomer, which was not observed when characterized by gas chromatography. Monoamine release activities of both MDMAR isomers were compared with the non‐selective monoamine releasing agent (+)‐3,4‐methylenedioxymethamphetamine (MDMA) as a standard reference compound. For additional comparison, both cis‐ and trans‐4,4′‐DMAR, were assessed under identical conditions. cis‐MDMAR, trans‐MDMAR, cis‐4,4′‐DMAR and trans‐4,4′‐DMAR were more potent than MDMA in their ability to function as efficacious substrate‐type releasers at the dopamine (DAT) and norepinephrine (NET) transporters in rat brain tissue. While cis‐4,4′‐DMAR, cis‐MDMAR and trans‐MDMAR were fully efficacious releasing agents at the serotonin transporter (SERT), trans‐4,4′‐DMAR acted as a fully efficacious uptake blocker. Currently, little information is available about the presence of MDMAR on the market but the high potency of ring‐substituted methylaminorex analogues at all three monoamine transporters investigated here might be relevant when assessing the potential for serious side‐effects after high dose exposure. Copyright © 2014 John Wiley & Sons, Ltd.     

A New Standard for Advance Care Planning (ACP) Conversations in the Hospital: Results from a Delphi Panel

BackgroundFewer than half of the US population has an advance healthcare directive. Hospitalizations offer a key opportunity for clinicians to engage patients in advance care planning (ACP) conversations. Guidelines suggest screening for the presence of “serious illness” but do not further specify how to prioritize the 12.4 million patients hospitalized each year.ObjectiveTo establish a normative standard for prioritizing hospitalized patients for ACP conversations.Design and SettingA modified Delphi study, with three iterative rounds of online surveys.ParticipantsMulti-disciplinary group of US-based clinicians with research and practical expertise in ACP.Main MeasuresIndirect and direct elicitation of short-term and 1-year risk of mortality that prompt experts to prioritize ACP conversations for hospitalized adults.Main resultsFifty-seven of 108 (52%) candidate panelists completed round 1, and 47 completed rounds 2 and 3. Panelists were primarily physicians (84%), with significant experience (mean years 23 [SD 9.8]), who either taught (55%) and/or performed research about ACP (55%). In round 1, > 70% of panelists agreed that all hospitalized adults ≥ 65 years should have an ACP conversation before discharge, but disagreed about the timing and content of the conversation. By round 3, > 70% of participants agreed that patients with either high (> 10%) short-term or high (≥ 34%) 1-year risk of mortality should have a goals of care conversation (i.e., focused on preferences for near-term treatment), while patients with low (≤ 10%) short-term and low (< 19%) 1-year risk of mortality warranted an ACP conversation (i.e., focused on preferences for future care) before discharge.LimitationsUse of case vignettes to elicit clinician judgment; response rate.ConclusionsPanelists agreed that clinicians should have an ACP conversation with all hospitalized adults over 65 years in an ACP conversation, adjusting the content and timing of the conversation conditional on the patient’s risk of short-term and 1-year mortality.Electronic supplementary materialThe online version of this article (10.1007/s11606-020-06150-0) contains supplementary material, which is available to authorized users.KEY WORDS: advance care planning, Delphi survey, physician performance

Numerous stakeholders recommend advance care planning (ACP) to improve the quality of care that patients receive as they approach the end-of-life.^1–3 Hospitalizations offer one opportunity for clinicians to initiate ACP conversations with patients.⁴ However, high-quality conversations, which allow patients to reveal (or potentially construct) their preferences, require clinicians to have the communication skills, the willingness to engage in emotionally complex interactions, and the time necessary to facilitate this process.^5–8 Guidelines suggest screening patients to prioritize those with near-term mortality or morbidity risk based on the presence of “serious illness,” defined as the presence of a condition that carries a high risk of mortality or impacts quality of life.⁴ In the absence of a quantifiable definition of this term, the surprise question (which requires the treating clinician to consider whether or not he/she would be surprised if the patient died in the next year) has been widely promoted.^{9, 10} Pooled results of two different meta-analyses, however, suggest poor to modest accuracy of the surprise question for predicting death at 12 months.^{10, 11} Efforts to improve the quality of care for patients at the end-of-life therefore require better strategies to screen and prioritize patients for ACP conversations.The objective of this study was to establish a consensus-based normative standard for risk of mortality that should prompt hospitalists to have an ACP conversation with their patients. Recognizing that people, even experts, struggle with probability-based judgments, we embedded a behavioral experiment within a Delphi process, sequentially presenting experts with cases selected from across the distribution of mortality risk and observing their judgments as the sampling frame changed. We hypothesized that experts would be more likely to recommend an immediate ACP conversation as the risk of mortality increased.     

Validation of fitness tracker for sleep measures in women with asthma

Objective: Nighttime wakening with asthma symptoms is a key to assessment and therapy decisions, with no gold standard objective measure. The study aims were to (1) determine the feasibility, (2) explore equivalence, and (3) test concordance of a consumer-based accelerometer with standard actigraphy for measurement of sleep patterns in women with asthma as an adjunct to self-report. Methods: Panel study design of women with poorly controlled asthma from a university-affiliated primary care clinic system was used. We assessed sensitivity and specificity, equivalence and concordance of sleep time, sleep efficiency, and wake counts between the consumer-based accelerometer Fitbit Charge? and Actigraph wGT3X+. We linked data between devices for comparison both automatically by 24-hour period and manually by sleep segment. Results: Analysis included 424 938?minutes, 738 nights, and 833 unique sleep segments from 47 women. The fitness tracker demonstrated 97% sensitivity and 40% specificity to identify sleep. Between device equivalence for total sleep time (15 and 42-minute threshold) was demonstrated by sleep segment. Concordance improved for wake counts and sleep efficiency when adjusting for a linear trend. Conclusions: There were important differences in total sleep time, efficiency, and wake count measures when comparing individual sleep segments versus 24-hour measures of sleep. Fitbit overestimates sleep efficiency and underestimates wake counts in this population compared to actigraphy. Low levels of systematic bias indicate the potential for raw measurements from the devices to achieve equivalence and concordance with additional processing, algorithm modification, and modeling. Fitness trackers offer an accessible and inexpensive method to quantify sleep patterns in the home environment as an adjunct to subjective reports, and require further informatics development.     

Preparedness Planning for Emergencies Among Postpartum Women in Arkansas During 2009

PurposeHaving an emergency plan may reduce negative effects of disaster on the health of postpartum women and their infants. However, little is known about the prevalence of emergency plans among postpartum women. In 2009, Arkansas added a question to the Pregnancy Risk Assessment Monitoring System surveillance system about whether women who gave birth that year had an emergency plan. In this study, we first describe the sociodemographic characteristics, disaster experience, and region of residence of postpartum women in Arkansas who indicated that they had an emergency plan for their families in 2009, and second, examine associations between sociodemographic characteristics and disaster experience and the presence of an emergency plan.MethodsMultivariable logistic regression (n = 1,173) was conducted to examine associations between maternal race/ethnicity, sociodemographic characteristics, region of residence, disaster experience, and having a disaster plan. We adjusted for maternal education, federal poverty level, and family size in our final model.FindingsForty-eight percent (n = 559) of women reported having an emergency plan. Hispanic women were less likely to report having a plan compared with non-Hispanic White women (n = 102 [10%]; adjusted prevalence ratio [aPR], 0.6; 95% confidence interval [CI], 0.4–0.9). Families with five or more members were more likely to have a plan compared with smaller families (n = 123 [11%]; aPR, 1.3; 95% CI, 1.1–1.6).ConclusionsPolicymakers and public health practitioners can use these results to promote emergency planning among postpartum women in Arkansas, with special outreach to postpartum women who are Hispanic or have smaller families.     

Identification of Possible Virulence Marker from Campylobacter jejuni Isolates

A novel protein translocation system, the type-6 secretion system (T6SS), may play a role in virulence of Campylobacter jejuni. We investigated 181 C. jejuni isolates from humans, chickens, and environmental sources in Vietnam, Thailand, Pakistan, and the United Kingdom for T6SS. The marker was most prevalent in human and chicken isolates from Vietnam.     

Coffee,caffeine, and risk of completed suicide: Results from three prospective cohorts of American adults

Objective.To evaluate the association between coffee and caffeine consumption and suicide risk in three large-scale cohorts of US men and women. Methods. We accessed data of 43,599 men enrolled in the Health Professionals Follow-up Study (HPFS, 1988–2008), 73,820 women in the Nurses’ Health Study (NHS, 1992–2008), and 91,005 women in the NHS II (1993–2007). Consumption of caffeine, coffee, and decaffeinated coffee, was assessed every 4 years by validated food-frequency questionnaires. Deaths from suicide were determined by physician review of death certificates. Multivariate adjusted relative risks (RRs) were estimated with Cox proportional hazard models. Cohort specific RRs were pooled using random-effect models. Results. We documented 277 deaths from suicide. Compared to those consuming ≤ 1 cup/week of caffeinated coffee (< 8 oz/237 ml), the pooled multivariate RR (95% confidence interval [CI]) of suicide was 0.55 (0.38–0.78) for those consuming 2–3 cups/day and 0.47 (0.27–0.81) for those consuming ≥ 4 cups/day (P trend < 0.001). The pooled multivariate RR (95% CI) for suicide was 0.75 (0.63–0.90) for each increment of 2 cups/day of caffeinated coffee and 0.77 (0.63–0.93) for each increment of 300 mg/day of caffeine. Conclusions. These results from three large cohorts support an association between caffeine consumption and lower risk of suicide.     

Skin pigmentation and genetic variants in an admixed Brazilian population of primarily European ancestry

International Journal of Legal Medicine - Although many genes have been shown to be associated with human pigmentary traits and forensic prediction assays exist (e.g. HIrisPlex-S), the genetic...     

Levels of satisfaction with rheumatoid arthritis treatment and associated alignment between physicians and patients across Latin America

Clinical Rheumatology - Discordance (misalignment) regarding treatment satisfaction may exist in real-life clinical practice between patients and their physicians. We aimed to assess physician and...