Ayahuasca and Dimethyltryptamine Adverse Events and Toxicity Analysis: A Systematic Thematic Review.

The objective of this paper is to conduct a systematic thematic review of adverse events, safety, and toxicity of traditional ayahuasca plant preparations and its main psychoactive alkaloids (dimethyltryptamine [DMT], harmine, harmaline, and tetrahydroharmine), including discussing clinical considerations (within clinical trials or approved settings). A systematic literature search of preclinical, clinical, epidemiological, and pharmacovigilance data (as well as pertinent reviews and case studies) was conducted for articles using the electronic databases of PubMed and Web of Science (to 6 July 2023) and PsycINFO, ClinicalTrials.gov, and Embase (to 21 September 2022) and included articles in English in peer-reviewed journals. Additionally, reference lists were searched. Due to the breadth of the area covered, we presented the relevant data in a thematic format. Our searches revealed 78 relevant articles. Data showed that ayahuasca or DMT is generally safe; however, some adverse human events have been reported. Animal models using higher doses of ayahuasca have shown abortifacient and teratogenic effects. Isolated harmala alkaloid studies have also revealed evidence of potential toxicity at higher doses, which may increase with co-administration with certain medications. Harmaline revealed the most issues in preclinical models. Nevertheless, animal models involving higher-dose synthetic isolates may not necessarily be able to be extrapolated to human use of therapeutic doses of plant-based extracts. Serious adverse effects are rarely reported within healthy populations, indicating an acceptable safety profile for the traditional use of ayahuasca and DMT in controlled settings. Further randomized, controlled trials with judicious blinding, larger samples, and longer duration are needed.

Burnout among Professionals Working in Corrections: A Two Stage Review.

Burnout is a state of emotional, physical, and mental exhaustion often caused by excessive and prolonged stress. Given the emotionally and often physically demanding nature of the work of correctional professionals, they are at substantial risk of suffering the adverse consequences of burnout. We systematically reviewed (Stage 1) the influence of burnout amongst forensic psychologists, psychiatrists, case workers, nurses, and correction officers. Interventions were then reviewed (Stage 2) at the individual and collective level to examine the effectiveness or efficacy of treatments for burnout among professionals working in corrections.

Exploring the Shared Experiences of Yazidis Who Survived Genocide.

In August 2014, the Islamic State of Iraq (ISIS) and the Levant (ISIL) brutally attacked the Yazidi people and occupied Sinjar and other villages in Northern Iraq. The massacre of Yazidis that began in August 2014 was declared by the United Nations as genocide. To gain a better understanding and raise awareness of these atrocities, we conducted a qualitative, phenomenological study with 35 Yazidis, who survived the genocide. The aim of the study was to elucidate the Yazidis' processing of the genocide and how it affects their psychological functioning. Coding and theming were the methods used to categorize, bring meaning and identity to Yazidis'genocidal experiences. The interviews took place between April and June 2019. Data analysis of the interview transcripts revealed that Yazidis, who survived the genocide of 2014, commonly experienced 11 themes related to hopelessness, fear, loss, grief, distrust, change, advocacy, optimism, shock, intrusive memories, and guilt. Results from this study reveal the vulnerabilities of ethnic minorities at risk of being abducted, killed, raped, and displaced. Moreover, the inherent risk of future genocides is illustrated through the experiences shared by the Yazidis.

Effects of coadministration of corn oil and ponazuril on serum and cerebrospinal fluid concentrations of ponazuril in horses.

BACKGROUND: Ponazuril is used for the treatment of equine protozoal myeloencephalitis (EPM). Coadministration of ponazuril with oil could result in higher serum and cerebrospinal fluid (CSF) concentrations of ponazuril. HYPOTHESIS: Coadministration of corn oil will result in higher serum and CSF concentrations of ponazuril than when ponazuril is administered alone. ANIMALS: Ten resident university-owned adult horses of either sex and >2 years of age. METHODS: Cohort study. Ponazuril oral paste (5 mg/kg BW; ponazuril treatment group (PON); n = 5), or ponazuril oral paste (5 mg/kg BW; ponazuril and oil treatment group (PONOIL; n = 5) coadministered with 2 oz of corn oil q24h for 21 days. Horses were treated once daily, for 21 days. Blood was collected on days 0, 7, 14, and 21 before dosing. In addition, CSF was collected on days 1, 7, 14, and 21. The concentration of ponazuril was determined in serum and CSF and results compared using repeated measures ANOVA. RESULTS: Coadministration of ponazuril with 2 oz of corn oil resulted in higher concentrations of ponazuril in serum (at steady state) than that found in horses given ponazuril alone (6.2 ± 0.9 mg/L versus 4.5 ± 1.0 mg/L; P = .004) (mean ± 1 SD). Cerebrospinal fluid concentrations of ponazuril were also greater in horses that received ponazuril and oil (0.213 mg/L ± 0.04 versus 0.162 ± 0.04 mg/L) (P = .03). CONCLUSIONS AND CLINICAL IMPORTANCE: Results suggest that coadministration of corn oil with ponazuril might enhance the effectiveness of treatment with ponazuril.

A meta-analysis of the Miller Forensic Assessment of Symptoms Test (M-FAST).

The Miller Forensic Assessment of Symptoms Test (M-FAST) is a screening instrument created to assess for potential malingering. The aim of this study was to conduct a meta-analysis to evaluate the extent to which the M-FAST total score can differentiate overreporters from comparison groups. Research reports were located through searching databases (e.g., PsycINFO) and the M-FAST published manual. A random-effects model was used with Hedges' g as the effect size to represent the difference between the overreporting and comparison groups' M-FAST total scores. Twenty-one research reports were included in the meta-analysis, providing 25 effect sizes with nonoverlapping samples. A very large effect size was observed (g = 2.26, 95% CI [1.91, 2.62]), indicating a substantial difference on the M-FAST total score between the two groups. Moderator analyses were conducted to identify characteristics that might explain effect size variability. A significant difference was found between effect sizes that were part of the M-FAST development (g = 3.82, 95% CI [2.82, 4.82]) and effect sizes independent from its development (g = 2.03, 95% CI [1.70, 2.36]). Using 12 research reports, random-effects analyses found an average sensitivity of 0.83 and average specificity of 0.85 for the M-FAST total score at the cut-off of ≥ 6. Based on the findings, research performed independently from the M-FAST development should be consulted when evaluating the validity of the total score interpretations. Because it is a screening instrument, an examinee should not be classified as malingering from the results of the M-FAST total score alone. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Are interprofessional healthcare teams meeting patient expectations? An exploration of the perceptions of patients and informal caregivers.

Poor teamwork skills in healthcare have been found to be a contributing cause of negative incidents in patient care, whilst effective teamwork has been linked to more positive patient outcomes. The aim of this research is to explore views of patients and informal caregivers on the key characteristics of effective healthcare teams and their experiences of healthcare teams using a qualitative approach. A focus group schedule was developed from existing literature to explore this. Topics included the purpose and value of teams in patient care, key attributes and their impact on patient care. Patients and informal caregivers were recruited via convenience sampling. Three focus groups were conducted. Thematic analysis identified a number of themes associated with effective teams. These themes included the perceived purpose of teams, perceptions about the structure of a team, team-based communication, the role of patients, delivery of care. Research participants noted the importance of key characteristics in effective teams, but felt that these were not always consistently present. Communication was considered to be the most important attribute in team working and also appeared to be the area in which the patient experience can be significantly improved. It is clear from the findings of this research that further improvements in teamwork skills in healthcare are needed to achieve effective collaborative practice, sustainable service delivery models and optimal patient care.

Development of a Rheumatology-specific Patient Concerns Inventory and Its Use in the Rheumatology Outpatient Clinic Setting.

OBJECTIVE: Successful management of rheumatic conditions involves increasing complexity of care. Delivering this in a holistic way is a growing challenge. The aim of our study was to develop a Patient Concerns Inventory (PCI) and assess it in the rheumatology clinic setting. METHODS: This observational exploratory study occurred with 2 phases. In phase I, the PCI was developed after a systematic literature search, expert opinion, and 3 patient focus group discussions. In phase II, the PCI was piloted in a general rheumatology clinic. RESULTS: Fifty-four patients were assessed in the pre-PCI group and 51 in the post-PCI group. Median (IQR) duration of consultation was 8 min (5-14) without PCI and 15 min (10-20) with PCI. The pre-PCI group raised 335 concerns from 50 patients, median (IQR) of 5 (3-10) per patient, rising post-PCI to 521 concerns, median (IQR) of 9 (5-16) from 51 patients, p = 0.002. Additional concerns predominantly arose from "physical and functional well-being" and "social care and well-being" domains. Most patients rated their experience with their doctor in the consultation as excellent or outstanding across all 11 questions in the questionnaire, both before and after the introduction of the PCI to the clinic setting. CONCLUSION: The PCI is a useful holistic needs assessment tool for rheumatology clinics. Although its use may initially prolong the consultation slightly, patients can raise a significantly higher number of concerns, which does not occur at the expense of patient satisfaction. This may help in identifying areas of unmet needs that previously went unnoticed.

Is There Any Benefit of Neuromonitoring During Descending and Thoracoabdominal Aortic Aneurysm Repair?

OBJECTIVE: Paraplegia remains the most feared and a devastating complication after descending and thoracoabdominal aneurysm operative repair (DTA and TAAAR). Neuromonitoring, particularly use of motor-evoked potentials (MEPs), for this surgery has gained popularity. However, ambiguity remains regarding its use and benefit. We systematically reviewed the literature to assess the benefit and applicability of neuromonitoring in DTA and TAAAR. METHODS: Electronic searches were performed on 4 major databases from inception until February 2014 to identify relevant studies. Eligibility decisions, method quality, data extraction, and analysis were performed according to predefined clinical criteria and end points. RESULTS: Among the studies matching our inclusion criteria, 1297 patients had MEP monitoring during DTA and TAAAR. In-hospital mortality was low (6.9% ± 3.6). Immediate neurological deficit was low (3.5% ± 2.6). In one third of patients (30.4% ± 14.2), the MEPs dropped below threshold, which were 30.4% and 29.4% with threshold levels of 75% and 50%, respectively. A range of surgical techniques were applied after reduction in MEPs. Most patients whose MEPs dropped and remained below threshold had immediate permanent neurological deficit (92.0% ± 23.6). Somatosensory-evoked potentials were reported in one third of papers with little association between loss of somatosensory-evoked potentials and permanent neurological deficit (16.7% ± 28.9%). CONCLUSIONS: We demonstrate that MEPs are useful at predicting paraplegia in patients who lose their MEPs and do not regain them intraoperatively. To date, there is no consensus regarding the applicability and use of MEPs. Current evidence does not mandate or support MEP use.

How competent do graduates feel to undertake the skills required by the General Medical Council?

The General Medical Council outlines the skills medical students are meant to learn as undergraduates. This article summarizes how competent some foundation year one doctors from one deanery felt to undertake these skills, what had prepared them and what they would like more training on.

Allopurinol for the treatment of chronic kidney disease: a systematic review.

BACKGROUND: The term chronic kidney disease (CKD) is used to describe abnormal kidney function (or structure). People with CKD have an increased prevalence of cardiovascular disease (CVD). Evidence is emerging that allopurinol may have a role to play in slowing down the progression of CKD and reducing the risk of CVD. OBJECTIVES: This systematic review addresses the research question: does allopurinol reduce mortality, the progression of chronic kidney disease or cardiovascular risk in people with CKD? DATA SOURCES: The following databases were searched on 7 January 2013: MEDLINE (1946 to 7 January 2013), EMBASE (1974 to 28 December 2012), The Cochrane Library (Issue 1, 2013) and ClinicalTrials.gov. Bibliographies of retrieved citations were also examined and two manufacturers of allopurinol were approached for data. REVIEW METHODS: Two reviewers independently screened all titles and abstracts to identify potentially relevant studies for inclusion in the review. Full-text copies were assessed independently by two reviewers. Data were extracted and assessed for risk of bias by one reviewer and independently checked for accuracy by a second. Summary statistics were extracted for each outcome and, where possible, data were pooled. Meta-analysis was carried out using fixed-effects models. RESULTS: Efficacy evidence was derived solely from four randomised controlled trials (RCTs). Adverse event (AE) data were derived from the RCTs and 21 observational studies. Progression of CKD was measured by estimated glomerular filtration rate (eGFR) in three trials and by changes in serum creatinine in the other. No significant differences in eGFR over time were reported. The only significant difference between groups was reported in one trial at 24 months favouring allopurinol [eGFR: 42.2 ml/minute/1.73 m(2), standard deviation (SD) 13.2 vs. 35.9 ml/minute/1.73 m(2), SD 12.3 ml/minute/1.73 m(2); p < 0.001]. In this same trial, there were twice as many cardiovascular events in the control arm (27%) as in the allopurinol arm (12%). Another trial reported an improvement in CKD progression as measured by serum creatinine in the allopurinol arm. No significant differences were reported in blood pressure between treatment groups in the meta-analyses. The incidence of AEs was estimated to be around 9% from all studies. The incidence of severe cutaneous adverse reactions (SCARs), which typically occurred within the first 2 months after allopurinol commencement, was reported to be 2% in two studies. Evidence for whether or not AEs and SCARs were dose related was conflicting. Not all patients had CKD in these studies. LIMITATIONS: None of the included studies reported concealment of allocation, one of the greatest risks to study validity. Relatively few (< 115) patients were enrolled in any RCT. For studies reporting AEs, the main limitation is the heterogeneity across studies. No studies examining quality-of-life measures were identified. CONCLUSIONS: There is limited evidence that allopurinol reduces CKD progression or cardiovascular events. It appears that AEs and in particular serious adverse events attributable to allopurinol are rare. However, the exact incidence of AEs in patients with CKD is unknown. Direct evidence for the impact of allopurinol on quality of life is lacking. Given the uncertainties in the evidence base, additional RCT evidence comparing allopurinol with usual care is required, accompanied by supporting data from observational studies of patients with CKD and using allopurinol. STUDY REGISTRATION: The study is registered as PROSPERO CRD42013003642. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Conformal invariance of the 3D self-avoiding walk.

We show that if the three-dimensional self-avoiding walk (SAW) is conformally invariant, then one can compute the hitting densities for the SAW in a half-space and in a sphere. We test these predictions by Monte Carlo simulations and find excellent agreement, thus providing evidence that the SAW is conformally invariant in three dimensions.

Cross-sectional study of prescribing errors in patients admitted to nine hospitals across North West England.

OBJECTIVE: To evaluate the prevalence, type and severity of prescribing errors observed between grades of prescriber, ward area, admission or discharge and type of medication prescribed. DESIGN: Ward-based clinical pharmacists prospectively documented prescribing errors at the point of clinically checking admission or discharge prescriptions. Error categories and severities were assigned at the point of data collection, and verified independently by the study team. SETTING: Prospective study of nine diverse National Health Service hospitals in North West England, including teaching hospitals, district hospitals and specialist services for paediatrics, women and mental health. RESULTS: Of 4238 prescriptions evaluated, one or more error was observed in 1857 (43.8%) prescriptions, with a total of 3011 errors observed. Of these, 1264 (41.9%) were minor, 1629 (54.1%) were significant, 109 (3.6%) were serious and 9 (0.30%) were potentially life threatening. The majority of errors considered to be potentially lethal (n=9) were dosing errors (n=8), mostly relating to overdose (n=7). The rate of error was not significantly different between newly qualified doctors compared with junior, middle grade or senior doctors. Multivariable analyses revealed the strongest predictor of error was the number of items on a prescription (risk of error increased 14% for each additional item). We observed a high rate of error from medication omission, particularly among patients admitted acutely into hospital. Electronic prescribing systems could potentially have prevented up to a quarter of (but not all) errors. CONCLUSIONS: In contrast to other studies, prescriber experience did not impact on overall error rate (although there were qualitative differences in error category). Given that multiple drug therapies are now the norm for many medical conditions, health systems should introduce and retain safeguards which detect and prevent error, in addition to continuing training and education, and migration to electronic prescribing systems.

How can we improve online HIV and STD prevention for men who have sex with men? Perspectives of hook-up website owners, website users, and HIV/STD directors.

Internet-based interventions have potential to reduce HIV and STD transmission among men who meet male sexual partners online. From November 2009 to May 2010 we surveyed dating and hook-up website users (n = 3,050), website owners (n = 18), and health department HIV/STD directors (n = 81) to identify structural and behavioral prevention interventions that could be implemented online and which a majority of website users were willing to use, owners were willing to implement, and HIV/STD directors perceived to be effective. A majority of each of the three stakeholder groups agreed on the following: (1) automated HIV/STD testing reminders, (2) local STD test site directories, (3) links to sex-positive safe sex videos, (4) access to sexual health experts, (5) profile options to include safer sex preference, (6) chat rooms for specific sexual interests, (7) filtering partners by their profile information, and (8) anonymous e-card partner notification for STD exposure. Findings help build consensus about how to prioritize resources for implementing online HIV and STD prevention interventions and highlight differences between stakeholders to guide future discussion about how to advance prevention efforts.

Challenges in implementing government-directed VTE guidance for medical patients: a mixed methods study.

BACKGROUND: Implementing venous thromboembolism (VTE) risk assessment guidance on admission to hospital has proved difficult worldwide. In 2010, VTE risk assessment in English hospitals was linked to financial sanctions. This study investigated possible barriers and facilitators for VTE risk assessment in medical patients and evaluated the impact of local and national initiatives. SETTING: Acute Medical Unit in one English National Health Service university teaching hospital. METHODS: This was a mixed methods study; National Research Ethics Service approval was granted. Data were collected over four 1-week periods; November 2009 (1), January 2010 (2), April 2010 (3) and April 2011 (4). Case notes for all medical patients admitted during these periods were reviewed. Thirty-six staff were observed admitting 71 of these patients; 24 observed staff participated in a structured interview. RESULTS: 876 case notes were reviewed. In total, 82.1% of patients had one or more VTE risk factors and 25.3% one or more bleeding risks. VTE risk assessment rose from a baseline of 6.9-19.6%, following local initiatives, and to 98.7% following financially sanctioned government targets. A similar increase in appropriate prescribing of prophylaxis was seen, but inappropriate prescribing also rose. No staff observed in period 1 conducted VTE risk assessment, risk-assessment forms were largely ignored or discarded during period 2; and electronic recording systems available during period 3 were not accessed. Few patients were asked any VTE-related questions in periods 1, 2 or 3. Interviewees' actual knowledge of VTE risk was not related to perceived knowledge level. Eight of the 24 staff interviewed were aware of national policies or guidance: none had seen them. Principal barriers identified to risk assessment were: involvement of multiple staff in individual admissions; interruptions; lack of policy awareness; time pressure and complexity of tools. CONCLUSIONS: National financial sanctions appear effective in implementing guidance, where other local measures have failed.

Opioid-mediated regulation of A11 diencephalospinal dopamine neurons: pharmacological evidence of activation by morphine.

Dopamine (DA) neurons of the A11 diencephalospinal system represent the sole source of DA innervation to the spinal cord in mice, serving neuromodulatory roles in the processing of nociceptive input and movement. These neurons originate in the dorso-caudal diencephalon and project axons unilaterally throughout the rostrocaudal extent of the spinal cord, terminating predominantly in the dorsal horn. The density of A11 DA axon terminals in the lumbar region is greater in males compared to females, while in both sexes the activity of neurons terminating in the thoracic spinal cord is greater than those terminating in the lumbar region. The present study was designed to test the hypothesis that A11 DA neurons are activated by opioids. To test this hypothesis, male and female mice were systemically treated with agonists or antagonists acting at the µ-opioid receptor, and spinal cord concentrations of DA and its metabolite DOPAC were determined in the thoracic and lumbar spinal cord using high performance liquid chromatography coupled with electrochemical detection. Systemic administration of the µ-opioid agonist morphine led to a dose- and time-dependent increase in spinal cord DOPAC/DA ratio (an estimate of DA neuronal activity) in both male and female mice, with greater changes occurring in the lumbar segment. Blockade of opioid receptors with the opioid antagonist naloxone reversed the stimulatory effects of morphine on A11 DA neurons in both male and female mice, but had little to no effect on the activity of these neurons when administered alone. Present findings are consistent with the conclusion that spinal cord-projecting axon terminals of A11 DA neurons are activated by opioids in both male and female mice, most likely through a dis-inhibitory mechanism.

Intellectual, behavioral, and personality correlates of violent vs. non-violent juvenile offenders.

The overall aim of this study was to examine the relationship between offender status (violent vs. nonviolent) and selected predictor variables from personality, behavioral, and intellectual domains. The two main sub goals were (a) to determine which variables from these domains were most closely associated with offender status, and (b) to construct a stepwise logistic regression model that could help identify which juveniles were more likely to be incarcerated for violent vs. nonviolent offenses. The participants for this investigation were juvenile offenders referred to the Juvenile Court Assessment Center by the Juvenile Justice Division of the Eleventh Judicial Circuit. The court-ordered assessment included the following measures: (a) The Millon Adolescent Clinical Inventory (MACI), (b) the Behavior Assessment System for Children (BASC), (c) the Peabody Picture Vocabulary Test-Third Edition (PPVT-III), (d) the Wide Range Achievement Test-Third Edition (WRAT-III), (e) the Kaufman Brief Intelligence Test (K-BIT), and (f) records of school achievement. The ten variables that had the strongest association with offender status were entered into the stepwise logistic regression analysis; five of these strategically chosen predictor variables accurately differentiated violent from nonviolent offenders 86.3% of the time. Reading Percentile (ß=-.051), PPVT-III (ß=-.059), MACI-Inhibition (ß=-.033), MACI-Eating Dysfunction (ß=.051), and BASC-Sense of Inadequacy (ß=-.072). Gender differences were explored.

The development of the irritable bowel syndrome-behavioral responses questionnaire.

OBJECTIVE: Unhelpful behavior related to irritable bowel syndrome (IBS) is often targeted and expected to change in treatments such as cognitive behavioral therapies. However, no scale has previously been produced to assess these dimensions. The aim of this study was to develop and validate an IBS-specific behavioral responses questionnaire. METHODS: A total of 153 patients with IBS as diagnosed by a general practitioner completed the 28-item Irritable Bowel Syndrome-Behavioral Responses Questionnaire (IBS-BRQ). A total of 117 persons without IBS also completed the IBS-BRQ and were used as a control group. Tests of internal consistency and principal components analyses (PCAs) were performed on both sets of data. RESULTS: The scale was found to be both reliable and valid with a high degree of internal consistency for both IBS patients (Cronbach's alpha=.86) and controls (Cronbach's alpha=.89). The scale differentiated significantly between IBS patients and controls (F=221, P<.01). The PCA supported a two-factor solution in both sets of data. Two items were removed from the scale due to low discriminative ability. The criterion validity was high as evidenced by a strong correlation with the Cognitive Scale for Functional Bowel Disorders (CS-FBD) (r =.67, P<.001). CONCLUSION: The IBS-BRQ is a valid and reliable scale that can be used for clinical as well as empirical purposes.

Predictors of treatment outcome after cognitive behavior therapy and antispasmodic treatment for patients with irritable bowel syndrome in primary care.

OBJECTIVE: To examine predictors of treatment outcome in IBS-patients who participated in a randomized controlled trial in primary care, where 149 irritable bowel syndrome (IBS) patients were randomized to mebeverine hydrochloride (n=77) or mebeverine+cognitive behavior therapy (CBT) (n=72). CBT offered additional benefit over mebeverine alone. METHODS: Regression analyses were used to identify predictors of work and social adjustment 12 months after treatment ended. The intervention groups were analyzed separately in order to look at the separate effects in each group. RESULTS: Lower levels of psychological distress (anxiety and depression) at baseline predicted a good outcome in the mebeverine group [beta=0.388 (95% CI: 0.065-0.936), P=.025] but not in the mebeverine+CBT group. In the adjusted model for the mebeverine+CBT group less adaptive IBS related behavioral coping predicted a good outcome [beta=0.285 (95% CI: 0.002-0.210), P=.045]. CONCLUSION: Different factors are associated with outcome depending on the treatment received. At assessment clinicians should assess patients coping styles and may want to consider recommending CBT to those patients with IBS in primary care who are engaging in unhelpful coping behavior.