When Vaping Isn't Actually Safer: A Death From Toxic Alcohol Contaminated Vape Juice.

ABSTRACT: Vape juice is a diluent for e-cigarette active ingredients, nicotine or tetrahydrocannabinol (THC). Lack of strict regulation in vape juice production is a concern as ingredients and their concentrations may vary widely from the labeling.A 43-year-old woman was transported via ambulance to the hospital after ingesting homemade vape juice, presenting unresponsive with decerebrate posturing. She reportedly made a tincture combining a vape juice purchased online (containing "ethylene glycol") and THC for "endometriosis-related pain relief." Laboratory evaluation revealed anion gap metabolic acidosis, elevated serum lactate, and high serum osmolality. Urine fluoresced under Wood's lamp, and fomepizole was administered as an ethylene glycol antidote, but she expired the following afternoon. Clinical serum toxicology results returned after death revealed 235 mg/dL of methanol, and no ethylene glycol.Autopsy findings included ischemic changes of the gastrointestinal tract and cerebral edema with herniation. Postmortem toxicology performed on hospital admission blood revealed methanol (220 mg/dL), propylene glycol (59 mg/dL), Δ-9 THC and metabolites, and medications administered during hospitalization. The medical examiner determined the cause of death to be methanol and propylene glycol toxicity.To our knowledge, this is the first report of accidental death from ingestion of vape juice contaminated with toxic alcohol.

Method Validation Study of Dipstick Urinalysis as a Screening Tool for Sodium Nitrite Toxicity.

ABSTRACT: The incidence of suicide by intentional nitrite ingestion has increased since 2017. Limited options exist for commercial laboratory analysis for nitrite/nitrate. This study investigates the use of urine dipsticks for screening at autopsy for potential toxicity with sodium nitrite and, less commonly, alkyl nitrite. Archived samples of blood, urine, vitreous fluid, and gastric contents from 4 sodium nitrite/nitrate cases, 3 alkyl nitrite cases, and 4 control cases were tested using dipsticks. A rapid, strong positive result for nitrite was in the vitreous fluid of all 4-sodium nitrite/nitrate cases, along with 2 positive urine and 1 positive gastric. The 2 alkyl nitrite inhalation toxicity cases had no positive results. One alkyl nitrite ingestion case had a positive urine. The 4 controls had negative urine: equivocal results in 2 vitreous, and 1 positive gastric. Urine dipsticks are a useful adjunct to laboratory testing for nitrite toxicity and provide a rapid, cost-effective tableside result that may guide the need for further testing. Vitreous fluid and urine appear to be the most reliable specimens, although testing of gastric liquid may be useful to corroborate oral ingestion. Dipsticks may not be a reliable adjunct for testing for alkyl nitrite toxicity via inhalation route, likely due to the much lower nitrite concentration compared to nitrite ingestion cases.

The RNA binding proteins LARP4A and LARP4B promote sarcoma and carcinoma growth and metastasis.

RNA-binding proteins (RBPs) are emerging as important regulators of cancer pathogenesis. We reveal that the RBPs LARP4A and LARP4B are differentially overexpressed in osteosarcoma and osteosarcoma lung metastases, as well as in prostate cancer. Depletion of LARP4A and LARP4B reduced tumor growth and metastatic spread in xenografts, as well as inhibiting cell proliferation, motility, and migration. Transcriptomic profiling and high-content multiparametric analyses unveiled a central role for LARP4B, but not LARP4A, in regulating cell cycle progression in osteosarcoma and prostate cancer cells, potentially through modulating key cell cycle proteins such as Cyclins B1 and E2, Aurora B, and E2F1. This first systematic comparison between LARP4A and LARP4B assigns new pro-tumorigenic functions to LARP4A and LARP4B in bone and prostate cancer, highlighting their similarities while also indicating distinct functional differences. Uncovering clear biological roles for these paralogous proteins provides new avenues for identifying tissue-specific targets and potential druggable intervention.

Self-Chiropractic Cervical Spinal Manipulation Resulting in Fatal Vertebral Artery Dissection: A Case Report and Review of the Literature.

ABSTRACT: Chiropractic cervical spinal manipulations have several complications and can result in vascular injury, including traumatic dissection of the vertebral arteries. A 43-year-old woman was admitted to the emergency department after performing a self-chiropractic spinal manipulation. She experienced headache and vomiting and was unresponsive with severe hypertension at the time of hospital admission. Clinical computerized tomography angiography showed narrowing of the right vertebral artery but was inconclusive for dissection or thrombosis. At autopsy, subacute dissection of the right vertebral artery was identified along with cerebral edema and herniation. A small peripheral pulmonary thromboembolism in the right lung was also seen. Neuropathology consultation confirmed the presence of diffuse cerebral edema and acute hypoxic-ischemic changes, with multifocal acute subarachnoid and intraparenchymal hemorrhage of the brain and spinal cord. This case presents a unique circumstance of a fatal vertebral artery dissection after self-chiropractic manipulation that, to the best of our knowledge, has not been previously described in the medical literature.

A realist evaluation of a London general practitioner trainer course.

Clinicians with teaching and training roles should be adequately trained and assessed. However, some debate exists as to what the nature of this training should be. Historically, a postgraduate certificate in education was a pre-requisite to becoming a GP trainer but this is changing with growing concern that such a pre-requisite might act as a deterrent to potential GP trainers. This research examines the impact of a scheme designed to provide an alternative, more practical and focused, pathway to becoming a GP trainer. We interviewed 26 course participants and stakeholders of the London GP Training Course (LGPTC), observed teaching sessions, and analysed course materials. We asked what elements of the course were and weren't effective, for whom, and under what circumstances. Here, we present a summary of our main findings - that GP trainers want to know practically, not theoretically, how to be a trainer; formative assessment boosts trainees' confidence in their own skills and abilities; short, practical GP training courses can help enhance the numbers of GP trainers; important questions remain about the role and value of educational theory in education faculty development.

Neck Hemorrhage: Fact or Artifact?-A Retrospective Analysis of Patterns of Postmortem Anterior Neck Muscle Hemorrhages From Hypostasis Versus Strangulation.

ABSTRACT: Distinguishing artifactual postmortem hypostatic hemorrhages from injury is key to accurately diagnosing strangulation. Despite being a well-known phenomenon, the literature is limited. This retrospective case-control analysis characterizes anterior neck musculature hemorrhage patterns associated with postmortem artifact versus strangulation by comparing incidental neck hemorrhages noted on 20 autopsy reports from 2020 to 2021 to 10 strangulation controls from 2015 to 2021 in Northern Nevada. Cases were analyzed for body position and location/severity of musculature involvement. For artifact cases, 50.0% were prone, 40.0% supine, and 10.0% side-lying. A total of 55.6% of artifact cases and controls demonstrated neck hemorrhage laterality. A total of 80.0% of the prone cases versus 77.8% of supine had diffuse hemorrhage versus focal. A total of 63.2% of artifact cases involved the sternocleidomastoid versus 70.0% controls (P = 1.000), 26.3% involved soft tissues versus 20.0% (P = 1.000), 9.1% the sternohyoid versus 40.0% (P = 0.149), 27.3% the sternothyroid versus 60.0% (P = 0.198), 9.1% the thyrohyoid versus 10.0% (P = 1.000), 18.2% the omohyoid versus 30.0% (P = 0.635), and 10.0% the tongue versus 50.0% (P = 0.026). Despite the limitations, this study demonstrated that while prone positioning is a contributing factor to the development of anterior neck hemorrhages, there are other factors than postmortem hypostasis.

Multicenter Phase I Trial of Ivosidenib as Maintenance Treatment Following Allogeneic Hematopoietic Cell Transplantation for IDH1-Mutated Acute Myeloid Leukemia.

PURPOSE: Isocitrate dehydrogenase 1 (IDH1) mutations occur in 5% to 10% of patients with acute myeloid leukemia (AML). Ivosidenib is an IDH1 inhibitor, approved for use in patients with IDH1-mutated AML. PATIENTS AND METHODS: We conducted a multicenter, phase I trial of maintenance ivosidenib following allogeneic hematopoietic cell transplantation (HCT) in patients with IDH1-mutated AML. Ivosidenib was initiated between days 30 and 90 following HCT and continued for up to 12 28-day cycles. The first dose level was 500 mg daily, with level reduction to 250 mg daily, if needed, in a 3 × 3 de-escalation design. Ten additional patients would then receive the MTD or recommended phase 2 dose (RP2D). The primary endpoint was establishing the MTD or RP2D of ivosidenib. RESULTS: Eighteen patients were enrolled, of whom 16 initiated post-HCT ivosidenib. One dose-limiting toxicity, grade(g) 3 QTc prolongation, was observed. The RP2D was established at 500 mg daily. Attributable g≥3 adverse events were uncommon, with the most common being QTc prolongation in 2 patients. Eight patients discontinued maintenance, with only one due to adverse event. Six-month cumulative incidence (CI) of gII-IV aGVHD was 6.3%, and 2-year CI of all cGVHD was 63%. Two-year CI of relapse and nonrelapse mortality (NRM) were 19% and 0%, respectively. Two-year progression-free (PFS) was 81%, and 2-year overall survival (OS) was 88%. CONCLUSIONS: Ivosidenib is safe and well-tolerated as maintenance therapy following HCT. Cumulative incidence of relapse and NRM, as well as estimations of PFS and OS, were promising in this phase I study.

Incisional hernia prevention: risk-benefit from a patient perspective (INVITE) - protocol for a single-centre, mixed-methods, cross-sectional study aiming to determine if using prophylactic mesh in incisional hernia prevention is acceptable to patients.

INTRODUCTION: Incisional hernia (IH) is a common complication of abdominal surgery affecting between 10% and 20% of patients and is associated with significant morbidity along with cost to the National Health Service. With high recurrence rates following repair, focus must be on prevention of IH rather than cure. There is an increasing evidence that patients at high risk of developing IH may benefit from prophylactic mesh placement during their index operation. With recent controversy surrounding the use of mesh in the UK, however, there is little understanding of whether this intervention would be acceptable to patients. METHODS AND ANALYSIS: INVITE is a mixed-methods, cross-sectional study to explore patient perceptions of the use of mesh as prophylaxis to prevent IH. Patients with and without IH who have undergone colorectal surgery between 2017 and 2020 in a single UK health-board will be approached to participate. 120 participants will be asked to complete a questionnaire and a subgroup of 24 participants will be invited to semistructured interviews. The primary outcome is to assess the acceptability of prophylactic mesh to patients. Secondary outcomes include understanding patients' knowledge of IH, and factors that may influence or alter the acceptability of mesh. Questionnaires have been developed using a 5-point Likert scale to allow quantitative analysis. Qualitative analysis of interviews will be conducted using NVivo software and thematic analysis. Data will be presented using the Journal Article Reporting Standards for mixed-methods research. ETHICS AND DISSEMINATION: Ethical approval has been granted by REC Wales (22/PR/0678), and the study is currently in setup. All participants will be required to provide informed consent prior to their participation in the study. We plan to report the results of the study in peer-reviewed scientific and medical journals and via presentations at scientific meetings. Results from this study will aid the design of interventional trials using prophylactic mesh. TRIAL REGISTRATION NUMBER: NCT05384600.

Enasidenib as maintenance following allogeneic hematopoietic cell transplantation for IDH2-mutated myeloid malignancies.

IDH2 (isocitrate dehydrogenase 2) mutations occur in approximately 15% of patients with acute myeloid leukemia (AML). The IDH2 inhibitor enasidenib was recently approved for IDH2-mutated relapsed or refractory AML. We conducted a multi-center, phase I trial of maintenance enasidenib following allogeneic hematopoietic cell transplantation (HCT) in patients with IDH2-mutated myeloid malignancies. Two dose levels, 50mg and 100mg daily were studied in a 3 × 3 dose-escalation design, with 10 additional patients treated at the recommended phase 2 dose (RP2D). Enasidenib was initiated between days 30 and 90 following HCT and continued for twelve 28-day cycles. Twenty-three patients were enrolled, of whom 19 initiated post-HCT maintenance. Two had myelodysplastic syndrome, and 17 had AML. All but 3 were in first complete remission. No dose limiting toxicities were observed, and the RP2D was established at 100mg daily. Attributable grade ≥3 toxicities were rare, with the most common being cytopenias. Eight patients stopped maintenance before completing 12 cycles, due to adverse events (n=3), pursuing treatment for graft-vs-host disease (GVHD) (n=2), clinician choice (n=1), relapse (n=1), and COVID infection (n=1). No cases of grade ≥3 acute GVHD were seen, and 12-month cumulative incidence of moderate/severe chronic GVHD was 42% (20-63%). Cumulative incidence of relapse was 16% (95% CI: 3.7-36%); 1 subject relapsed while receiving maintenance. Two-year progression-free and overall survival were 69% (95% CI: 39-86%) and 74% (95% CI, 44-90%), respectively. Enasidenib is safe, well-tolerated, with preliminary activity as maintenance therapy following HCT, and merits additional study. The study was registered at www.clinicaltrials.gov (#NCT03515512).

Hughes abdominal closure versus standard mass closure to reduce incisional hernias following surgery for colorectal cancer: the HART RCT.

BACKGROUND: Incisional hernias can cause chronic pain and complications and affect quality of life. Surgical repair requires health-care resources and has a significant associated failure rate. A prospective, multicentre, single-blinded randomised controlled trial was conducted to investigate the clinical effectiveness and cost-effectiveness of the Hughes abdominal closure method compared with standard mass closure following surgery for colorectal cancer. The study randomised, in a 1 : 1 ratio, 802 adult patients (aged ≥ 18 years) undergoing surgical resection for colorectal cancer from 28 surgical departments in UK centres. INTERVENTION: Hughes abdominal closure or standard mass closure. MAIN OUTCOME MEASURES: The primary outcome was the incidence of incisional hernias at 1 year, as assessed by clinical examination. Within-trial cost-effectiveness and cost-utility analyses over 1 year were conducted from an NHS and a social care perspective. A key secondary outcome was quality of life, and other outcomes included the incidence of incisional hernias as detected by computed tomography scanning. RESULTS: The incidence of incisional hernia at 1-year clinical examination was 50 (14.8%) in the Hughes abdominal closure arm compared with 57 (17.1%) in the standard mass closure arm (odds ratio 0.84, 95% confidence interval 0.55 to 1.27; p = 0.4). In year 2, the incidence of incisional hernia was 78 (28.7%) in the Hughes abdominal closure arm compared with 84 (31.8%) in the standard mass closure arm (odds ratio 0.86, 95% confidence interval 0.59 to 1.25; p = 0.43). Computed tomography scanning identified a total of 301 incisional hernias across both arms, compared with 100 identified by clinical examination at the 1-year follow-up. Computed tomography scanning missed 16 incisional hernias that were picked up by clinical examination. Hughes abdominal closure was found to be less cost-effective than standard mass closure. The mean incremental cost for patients undergoing Hughes abdominal closure was £616.45 (95% confidence interval -£699.56 to £1932.47; p = 0.3580). Quality of life did not differ significantly between the study arms at any time point. LIMITATIONS: As this was a pragmatic trial, the control arm allowed surgeon discretion in the approach to standard mass closure, introducing variability in the techniques and equipment used. Intraoperative randomisation may result in a loss of equipoise for some surgeons. Follow-up was limited to 2 years, which may not have been enough time to see a difference in the primary outcome. CONCLUSIONS: Hughes abdominal closure did not significantly reduce the incidence of incisional hernias detected by clinical examination and was less cost-effective at 1 year than standard mass closure in colorectal cancer patients. Computed tomography scanning may be more effective at identifying incisional hernias than clinical examination, but the clinical benefit of this needs further research. FUTURE WORK: An extended follow-up using routinely collected NHS data sets aims to report on incisional hernia rates at 2-5 years post surgery to investigate any potential mortality benefit of the closure methods. Furthermore, the proportion of incisional hernias identified by a computed tomography scan (at 1 and 2 years post surgery), but not during clinical examination (occult hernias), proceeding to surgical repair within 3-5 years after the initial operation will be explored. TRIAL REGISTRATION: This trial is registered as ISRCTN25616490. FUNDING: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 34. See the NIHR Journals Library website for further project information.

Bowel cancer treatment involves surgery for the majority of patients. A complication of this surgery is the formation of a hernia at the site of the incision in the abdominal wall, known as an incisional hernia. The lining of the abdomen, fat or the intestine can squeeze through the gap and form a lump under the skin. An incisional hernia can form any time after surgery and can cause serious complications and pain, and can also affect the patient's quality of life. Surgery to correct incisional hernias is not always successful, so finding a way of preventing them is important. This research compares the traditional way of sewing up the abdomen, where the two sides are brought together in one layer with a continuous thread, with an alternative method called the Hughes abdominal closure method/Hughes repair. In the Hughes repair, a series of horizontal and vertical stitches are arranged to spread the load and ease the tension across the wound. A total of 802 patients from 28 sites in the UK were recruited to the trial. Half of the patients were randomly allocated to have traditional abdominal closure and half were randomised to have Hughes abdominal closure. All were followed up for 1 year after surgery to assess whether or not an incisional hernia had occurred. We also assessed quality of life during follow-up, and we compared the costs and benefits of each procedure to see which option was the better value for money. By comparing the results from the two methods, it was hoped that the best method of abdominal closure to reduce the risk of an incisional hernia occurring would be found. The analysis of the data suggested that the risk of an incisional hernia was no different with either closure method. Furthermore, Hughes abdominal closure was more expensive and provided less value for money than standard abdominal closure.

UroLift for Treating Lower Urinary Tract Symptoms of Benign Prostatic Hyperplasia: A NICE Medical Technology Guidance Update.

Lower urinary tract symptoms (LUTS) commonly occur as a consequence of benign prostatic hyperplasia (BPH), also known as prostate enlargement. Treatments for this can involve electrosurgical removal of a section of the prostate via transurethral resection of the prostate (TURP), Holmium laser enucleation of the prostate (HoLEP), or prostatic urethral lift using the UroLift system. The UroLift system implants to pull excess prostatic tissue away so that it does not narrow or block the urethra. In this way, the device is designed to relieve symptoms of urinary outflow obstruction without cutting or removing tissue. National guidance recommending the use of UroLift in the UK NHS was first issued in 2015 by the National Institute for Health and Care Excellence (NICE MTG26). We now report on the process to update the economic evaluation of UroLift, leading to updated NICE guidance published in May 2021 (NICE MTG58). The conclusions of the available clinical evidence were mixed and suggested that whilst UroLift improves symptoms over time, this improvement is smaller than that of TURP for symptom severity (IPSS) and urological outcomes. However, UroLift appears to be superior to Rezum for symptom severity and measures of erectile dysfunction and ejaculatory dysfunction. The updated economic model estimated that using UroLift as a day-case procedure for people with prostate of volume 30-80 mL creates a saving of £981 per person compared with bipolar TURP, £1242 compared with monopolar TURP, and £1230 compared with HoLEP.

Altered Brain Criticality in Schizophrenia: New Insights From Magnetoencephalography.

Schizophrenia has a complex etiology and symptomatology that is difficult to untangle. After decades of research, important advancements toward a central biomarker are still lacking. One of the missing pieces is a better understanding of how non-linear neural dynamics are altered in this patient population. In this study, the resting-state neuromagnetic signals of schizophrenia patients and healthy controls were analyzed in the framework of criticality. When biological systems like the brain are in a state of criticality, they are thought to be functioning at maximum efficiency (e.g., optimal communication and storage of information) and with maximum adaptability to incoming information. Here, we assessed the self-similarity and multifractality of resting-state brain signals recorded with magnetoencephalography in patients with schizophrenia patients and in matched controls. Schizophrenia patients had similar, although attenuated, patterns of self-similarity and multifractality values. Statistical tests showed that patients had higher values of self-similarity than controls in fronto-temporal regions, indicative of more regularity and memory in the signal. In contrast, patients had less multifractality than controls in the parietal and occipital regions, indicative of less diverse singularities and reduced variability in the signal. In addition, supervised machine-learning, based on logistic regression, successfully discriminated the two groups using measures of self-similarity and multifractality as features. Our results provide new insights into the baseline cognitive functioning of schizophrenia patients by identifying key alterations of criticality properties in their resting-state brain data.

A Case Study on Reviewing Specialist Services Commissioning in Wales: TAVI for Severe Aortic Stenosis.

The Welsh Health Specialised Services Committee (WHSSC) is responsible for planning, commissioning and funding specialised healthcare in Wales. Investment in new technologies or services is based on clinical and economic evidence, using a consistent and transparent process. This is accomplished in three stages. The first stage is the preparation of a rapid evidence review. This then informs the development or update of the relevant Commissioning Policy. The final stage is to prioritise the Commissioning Policy recommendations against all other new services and interventions, to inform WHSSC's annual commissioning intentions. In 2017, a review was conducted of the WHSSC Commissioning Policy for transcatheter aortic valve implantation for severe aortic stenosis. Prior to this only high-risk patients were eligible for transcatheter aortic valve implantation. The rapid evidence review identified three randomised controlled trials and two economic analyses relevant to the decision problem. Transcatheter aortic valve implantation was generally found to be more expensive and more effective than medical management or surgical aortic valve replacement, with incremental cost-effectiveness ratios around £10,500-£36,000 for inoperable groups and £17,000-£24,000 in high-risk groups. The rapid evidence review, expert advice and stakeholder feedback informed the revision process of the Commissioning Policy for transcatheter aortic valve implantation. This recommended the addition of patients unsuitable for surgical aortic valve replacement and the removal of explicit risk scoring. This recommendation was subject to the prioritisation process (carried out annually). The updated transcatheter aortic valve implantation recommendation was ranked second out of 23 technologies and services competing for additional WHSSC funding. The WHSSC Integrated Commissioning Plan for specialised services in Wales (2019) therefore included funding to support the new criteria for transcatheter aortic valve implantation treatment.

In Wales, specialised health services are selected and funded at a national level by the Welsh Health Specialised Services Committee. Specialised services are provided for small numbers of patients, requiring highly specialised professionals or technologies. When the aortic heart valve becomes narrowed with disease it can be replaced with an artificial valve. This normally requires open surgery, which is risky for some patients, particularly those who are frail. Since 2012, the Welsh Health Specialised Services Committee have funded a less invasive procedure called TAVI (transcatheter aortic valve implantation) for patients who could have open surgery but at a high risk. In 2017, this policy needed updating, thus a new evidence review was conducted. This showed that patients at high risk from open surgery were more likely to survive if they underwent TAVI. Others, for whom open surgery was too risky, were also more likely to survive if they underwent TAVI instead of medication. However, TAVI tended to produce more vascular problems, such as blockages or damage to blood vessels. Transcatheter aortic valve implantation is generally more effective and more expensive than either drugs or open surgery in these patient groups, but is within cost-effectiveness limits often used in the UK National Health Service. As a result of the review, experts recommended that TAVI should be available to more patients, which would require greater levels of funding. Transcatheter aortic valve implantation was ranked as second out of 23 new or updated treatments competing for funding allocations. The Welsh Health Specialised Services Committee therefore published a new Commissioning Plan for TAVI in 2019 that now included patients who are considered too risky to undergo open surgery.

Activation of a cGAS-STING-mediated immune response predicts response to neoadjuvant chemotherapy in early breast cancer.

BACKGROUND: The DNA-damage immune-response (DDIR) signature is an immune-driven gene expression signature retrospectively validated as predicting response to anthracycline-based therapy. This feasibility study prospectively evaluates the use of this assay to predict neoadjuvant chemotherapy response in early breast cancer. METHODS: This feasibility study assessed the integration of a novel biomarker into clinical workflows. Tumour samples were collected from patients receiving standard of care neoadjuvant chemotherapy (FEC + /-taxane and anti-HER2 therapy as appropriate) at baseline, mid- and post-chemotherapy. Baseline DDIR signature scores were correlated with pathological treatment response. RNA sequencing was used to assess chemotherapy/response-related changes in biologically linked gene signatures. RESULTS: DDIR signature reports were available within 14 days for 97.8% of 46 patients (13 TNBC, 16 HER2 + ve, 27 ER + HER2-ve). Positive scores predicted response to treatment (odds ratio 4.67 for RCB 0-1 disease (95% CI 1.13-15.09, P = 0.032)). DDIR positivity correlated with immune infiltration and upregulated immune-checkpoint gene expression. CONCLUSIONS: This study validates the DDIR signature as predictive of response to neoadjuvant chemotherapy which can be integrated into clinical workflows, potentially identifying a subgroup with high sensitivity to anthracycline chemotherapy. Transcriptomic data suggest induction with anthracycline-containing regimens in immune restricted, "cold" tumours may be effective for immune priming. TRIAL REGISTRATION: Not applicable (non-interventional study). CRUK Internal Database Number 14232.

Kratom-Associated Fatalities in Northern Nevada-What Mitragynine Level Is Fatal?

ABSTRACT: Mitragyna speciosa, commonly known as the kratom tree, has been utilized in Southeast Asia for centuries for its opioid-like effects. Kratom has been available in the United States for the past decade and has grown increasingly popular despite a lack of clinical research to determine its safety. With its widespread use, there have been an increasing number of fatalities. This study aims to establish a potential lethal range for mitragynine, the active compound in kratom, by investigating the toxicology reports of 35 deaths in Northern Nevada between 2015 and 2020. Mitragynine concentrations ranged from 8.7 to 1800 ng/mL (n = 27) in cases with drug toxicity as the cause of death; in 1 case, the sole intoxicant was mitragynine with a blood concentration of 950 ng/mL. In cases with nonmitragynine causes of death, the concentration was 110 to 980 ng/mL (n = 8). There was no statistically significant difference in blood concentrations between cases where mitragynine was not listed as a cause of death (mean, 315 ± 297.2 ng/mL) and cases in which mitragynine contributed to death (mean, 269.4 ± 382.5 ng/mL; P < 0.201). A literature review is also presented.

The PLASMA System for Transurethral Resection of the Prostate: A NICE Medical Technologies Guidance Update.

Lower urinary tract symptoms (LUTS) in men commonly occur as a consequence of benign prostatic hyperplasia (BPH), also known as prostate enlargement. Treatments for this can involve electrosurgical removal of a section of the prostate via transurethral resection of the prostate (TURP). This can be performed using either monopolar or bipolar electrosurgery. Bipolar TURP uses saline for irrigation rather than glycine, which drastically reduces the risk of TUR syndrome complications, thus allowing for increased procedure time if needed. The PLASMA system (formally known as TURis) is a bipolar TURP electrosurgery system used to treat LUTS secondary to BPH. National guidance recommending the use of TURis in the UK NHS was issued in 2014 by NICE and we now report the updated contribution from Cedar that was included in the update of that guidance for 2021. The evidence in this review suggests that the PLASMA system could be beneficial to patients in relation to hospitalisation and catheterisation time compared with monopolar TURP (mTURP). However, it appears to be comparable to mTURP for urological outcomes and worse for post-operative haematology outcomes such as decline in sodium and haemoglobin levels. Adverse events, however, occurred much less with PLASMA use.

Effects of the Argus II Retinal Prosthesis System on the Quality of Life of Patients With Ultra-Low Vision Due to Retinitis Pigmentosa: Protocol for a Single-Arm, Mixed Methods Study.

BACKGROUND: Retinitis pigmentosa is an incurable, degenerative retinal condition causing progressive sight loss, significantly affecting patients' quality of life. The Argus II Retinal Prosthesis is a surgically implanted medical device that delivers electrical stimulation to the retina. It is intended to produce a form of artificial vision for blind people with severe-to-profound retinitis pigmentosa by stimulating the remaining viable retinal cells to induce visual perception. This study has been initiated by National Health Service England's Commissioning through Evaluation program and funded through the National Institute of Health Research of the United Kingdom. OBJECTIVE: The aim of this study was to assess the effect of the Argus II device on patient's daily activities and quality of life. METHODS: This protocol is a prospective, single-arm, open-label, mixed methods study on 10 consecutive participants receiving the Argus II device. The patient representatives played an integral role in the design of this study. Eligibility criteria include ultra-low vision in both eyes as a result of end-stage retinitis pigmentosa and a willingness and capacity to complete the postimplantation rehabilitation program. Participants will be interviewed by independent researchers at baseline and 12 months later by using a semistructured, in-depth approach, alongside validated questionnaires (Impact of Vision Impairment-Very Low Vision, 5-level EuroQoL-5 dimensions scale, EuroQoL-visual analog scale, and Hospital Anxiety and Depression Scale) and a bespoke device-related questionnaire, which includes questions about users' experiences with the procedure, the device, and rehabilitation. The effect of the device on patients' functional vision and activities of daily living will be assessed by vision rehabilitation specialists using a set of tests measured on an ordinal scale (eg, ability to locate objects and avoid obstacles). Clinical outcomes include full-field stimulus light threshold, square localization, direction of motion, grating visual acuity, Landolt-C, procedural success, and adverse events. Qualitative and quantitative outcomes will be linked in a single database to enable individual participant measures to be considered in toto, comparing baseline to the final review. RESULTS: This study was approved by the local ethics committee on April 24, 2019 (London-Camberwell St. Giles Research Ethics Committee, reference 19/LO/0429). It has also been approved by the Health Research Authority and Health and Care Research Wales. At the time of protocol writing, Argus II was available for use in the United Kingdom; however, the manufacturer recently withdrew the Argus II device from sale in the United Kingdom. Therefore, the study is not going ahead at this time. CONCLUSIONS: The mixed methods approach provides a rich and in-depth assessment of the effect of the device on participants' quality of life. Despite the work not going ahead, the publication of this publicly funded protocol is important for researchers planning similar work. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/17436.

Mental health street triage: Comparing experiences of delivery across three sites.

WHAT IS ALREADY KNOWN ABOUT THE TOPIC?: MHST represents transformation at the forefront of policing and mental health to people in crisis with the aim of providing a better and more efficient response. Current knowledge has largely focused on service development, informed by narratives of risk, and this study applies an alternative focus by considering the interplay in practice. WHAT THE PAPER ADDS TO EXISTING KNOWLEDGE?: This paper adds to emerging work on mental health street triage, offering original insights into the interplay of police officers and mental health nurses in practice. The evidence presented shows how the dynamics between officers and nurses were informed by perceptions of trust, belonging and legitimacy which shaped decision-making and outcomes. This study also reveals the impacts of leadership continuity and staff turnover to service efficacy and the potential of strategic "drift." WHAT ARE THE IMPLICATIONS FOR PRACTICE?: Nurses who work in MHST operations should be prepared to share knowledge, learning and insight into how different mental health conditions present in practice and support the assessment of risk posed to officers. Alternative pathways available to detainment by police under the Mental Health Act should be identified and communicated to officers, both in the control room and in situ, to avoid unnecessary detentions. Strategies should be developed to extend the communication of mental health education and knowledge beyond those immediately involved in MHST to support the police to better respond to mental health. ABSTRACT: Introduction The limited evidence on mental health street triage (MHST) is largely focused on service development and is overly police-centric dominated by narratives of risk. This paper considers the interplay between officers and CPNs in practice situated within strategic and operational contexts, illustrating the importance of place to service developments and trust within practice. Aim This study was conducted to compare the processes, experiences and perceptions of MHST in three sites in England. Method Semi-structured interviews were completed with 27 police and health service staff in strategic and operational roles over a three-month period in three sites in England. Results Four themes were identified: "Reducing and improving the use of mental health detainments," "Importance of local contexts and partnerships," "Enhancing officer confidence" and "Developing street triage." Discussion Mental health street triage decision-making and outcomes were influenced by issues of trust, belonging and legitimacy within the interplay between officers and nurses. Continuity and staff turnover influenced strategic and operational development. However, MHST was perceived to be an effective and cost-saving model. Implications for practice Mental health nurses are well positioned to lead awareness and education of officers in relation to mental health crisis response. Staff need to develop communication strategies that extend beyond those immediately involved in MHST.

Dopamine and Glutamate in Antipsychotic-Responsive Compared With Antipsychotic-Nonresponsive Psychosis: A Multicenter Positron Emission Tomography and Magnetic Resonance Spectroscopy Study (STRATA).

The variability in the response to antipsychotic medication in schizophrenia may reflect between-patient differences in neurobiology. Recent cross-sectional neuroimaging studies suggest that a poorer therapeutic response is associated with relatively normal striatal dopamine synthesis capacity but elevated anterior cingulate cortex (ACC) glutamate levels. We sought to test whether these measures can differentiate patients with psychosis who are antipsychotic responsive from those who are antipsychotic nonresponsive in a multicenter cross-sectional study. 1H-magnetic resonance spectroscopy (1H-MRS) was used to measure glutamate levels (Glucorr) in the ACC and in the right striatum in 92 patients across 4 sites (48 responders [R] and 44 nonresponders [NR]). In 54 patients at 2 sites (25 R and 29 NR), we additionally acquired 3,4-dihydroxy-6-[18F]fluoro-l-phenylalanine (18F-DOPA) positron emission tomography (PET) to index striatal dopamine function (Kicer, min-1). The mean ACC Glucorr was higher in the NR than the R group after adjustment for age and sex (F1,80 = 4.27; P = .04). This was associated with an area under the curve for the group discrimination of 0.59. There were no group differences in striatal dopamine function or striatal Glucorr. The results provide partial further support for a role of ACC glutamate, but not striatal dopamine synthesis, in determining the nature of the response to antipsychotic medication. The low discriminative accuracy might be improved in groups with greater clinical separation or increased in future studies that focus on the antipsychotic response at an earlier stage of the disorder and integrate other candidate predictive biomarkers. Greater harmonization of multicenter PET and 1H-MRS may also improve sensitivity.