Subthreshold rejection activity in many kidney transplants currently classified as having no rejection.

Most kidney transplant patients who undergo biopsies are classified as having no rejection based on consensus thresholds. However, we hypothesized that because these patients have normal adaptive immune systems, T cell-mediated rejection (TCMR) and antibody-mediated rejection (ABMR) may exist as subthreshold activity in some transplants currently classified as no rejection. To examine this question, we studied genome-wide microarray results from 5086 kidney transplant biopsies (4170 patients). An updated archetypal analysis designated 56% of biopsies as no rejection. Subthreshold molecular TCMR and/or ABMR activity molecular activity was detectable as elevated classifier scores in many biopsies classified as no rejection, with ABMR activity in many TCMR biopsies and TCMR activity in many ABMR biopsies. In biopsies classified as no rejection histologically and molecularly, molecular TCMR classifier scores correlated with increases in histologic TCMR features and molecular injury, lower eGFR, and higher risk of graft loss, and molecular ABMR activity correlated with increased glomerulitis and donor-specific antibody. No rejection biopsies with high subthreshold TCMR or ABMR activity had a higher probability of having TCMR or ABMR respectively diagnosed in a future biopsy. We conclude that many kidney transplant recipients have unrecognized subthreshold TCMR or ABMR activity, with significant implications for future problems.

A Randomized Trial Comparing Imlifidase to Plasmapheresis in Kidney Transplant Recipients With Antibody-Mediated Rejection.

BACKGROUND: Antibody-mediated rejection (ABMR) poses a barrier to long-term graft survival and is one of the most challenging events after kidney transplantation. Removing donor specific antibodies (DSA) through therapeutic plasma exchange (PLEX) is a cornerstone of antibody depletion but has inconsistent effects. Imlifidase is a treatment currently utilized for desensitization with near-complete inactivation of DSA both in the intra- and extravascular space. METHODS: This was a 6-month, randomized, open-label, multicenter, multinational trial conducted at 14 transplant centers. Thirty patients were randomized to either imlifidase or PLEX treatment. The primary endpoint was reduction in DSA level during the 5 days following the start of treatment. RESULTS: Despite considerable heterogeneity in the trial population, DSA reduction as defined by the primary endpoint was 97% for imlifidase compared to 42% for PLEX. Additionally, imlifidase reduced DSA to noncomplement fixing levels, whereas PLEX failed to do so. After antibody rebound in the imlifidase arm (circa days 6-12), both arms had similar reductions in DSA. Five allograft losses occurred during the 6 months following the start of ABMR treatment-four within the imlifidase arm (18 patients treated) and one in the PLEX arm (10 patients treated). In terms of clinical efficacy, the Kaplan-Meier estimated graft survival was 78% for imlifidase and 89% for PLEX, with a slightly higher eGFR in the PLEX arm at the end of the trial. The observed adverse events in the trial were as expected, and there were no apparent differences between the arms. CONCLUSION: Imlifidase was safe and well-tolerated in the ABMR population. Despite meeting the primary endpoint of maximum DSA reduction compared to PLEX, the trial was unsuccessful in demonstrating a clinical benefit of imlifidase in this heterogenous ABMR population. TRIAL REGISTRATION: EudraCT number: 2018-000022-66, 2020-004777-49; ClinicalTrials.gov identifier: NCT03897205, NCT04711850.

Structural inequalities, knife crime: A qualitative study.

The importance and impact of youth violence is increasingly being recognised and is a cause of international concern. In the UK, youth violence, specifically knife crime, is on the increase and has resulted in the deaths of many young people. In order to explore the impact of knife crimes on mental health and wellbeing of individuals, a number of focus groups were conducted with 24 professionals from multiple agencies. Qualitative analysis showed various emerging themes, which included ineffective mental health systems, structural violence and inequalities, policing, safety and community engagement, vulnerability and resilience in minority communities. Equity in mental health services, further development and roll-out of public mental health approaches and training accompanied by sufficient resources is needed.

Youth violence and knife crime in ethnic minorities in the UK: A review of the literature.

BACKGROUND: Youth violence and knife crime is increasing dramatically, so much so it has been described as a global epidemic. The social, economic and political forces fuelling this rise mean that minority groups are particularly affected. AIM: This paper reviews the literature primarily from a UK perspective, and illustrates the disparate factors that are influencing the rise in youth violence and knife crime and illustrates the complexities of integrating the perspectives of different disciplines into coherent intervention strategies. METHOD: We conducted a systematic review of the literature that explores both the causes of increasing youth violence and knife crime as well as some of the interventions that have attempted to deal with the problem. RESULTS: A complex interplay of social, economic, mental health and political factors underpin the increase in youth violence and knife crime. An uneasy tension exists between a traditional criminal justice system-based approach based upon deterrence and punishment, and a more liberal preventative model focusing on adolescent mental health. None of the interventions thus far have been particularly effective. CONCLUSION: Youth violence and knife crime is a global social issue that causes untold suffering to individuals, families and communities as well as fear that reverberates through society. Interventions have often been devised through the lens of particular disciplines or ideologies. Integrating these perspectives into a coherent approach that is actually effective demands greater co-operation, dialogue and mutual understanding between disciplines and agencies, as well as a robust framework for the evidence-based assessment of outcomes.

A Continuing Pharmacy Education (CPE) Program Assessing Cannabidiol (CBD) Knowledge and Confidence Among Practicing Pharmacists.

Background: Increased patient utilization of cannabidiol (CBD) leads to potential drug interactions with various medications and questions posed to pharmacists. Objective: To quantify the knowledge gap of pharmacists on CBD and CBD-containing products and assess the degree a continuing pharmacy education (CPE) program alters pharmacist confidence and competency on CBD knowledge. Methods: A 1-h CPE activity was offered as a home study from May 9, 2022, through September 30, 2022. Subjects were practicing pharmacy preceptors in Alabama who completed the pre-survey and post-survey for inclusion in matched-pair analyses. The primary outcome measure was participant score improvement between the pre-post surveys. Secondary measures involved pre-post comparisons on self-rated Likert questions concerning participant confidence in counseling, answering drug information questions, and ensuring patient safety regarding CBD. Results: A total of 124 participants completed the course. After matched pairing, 64 and 56 individuals were included in the knowledge-based and confidence ranking analyses, respectively. Participant scoring improved on the knowledge-based questions between the pre-post surveys (50.0% vs 87.8%, P < .001). There was a significant confidence improvement of participants from baseline on counseling patients about prescription or over-the-counter CBD products, answering questions from other healthcare professionals about these products, and ensuring patient safety while using these products (Average 5-level Likert scale increases of 1.75, 1.73, 1.70, respectively; all P < .001). Conclusion: Implementation of a CPE program improved practicing pharmacists' knowledge on information about CBD, which lead to increased competency on counseling patients, answering drug information questions, and promoting patient safety.

Delay in diagnosis of urethral perforation due to catheterisation in a person with cervical spinal cord injury. Importance of (1) imaging studies done promptly for detection and documentation of urethral trauma, (2) Urethrotech catheterisation device to minimise urethral trauma and achieve successful catheterisation: A case report.

INTRODUCTION AND IMPORTANCE: Spinal cord injury patients are at risk for urethral trauma during catheterisation. We report a patient in whom urethral perforation due to catheterisation was not recognised for ∼ four days. CASE PRESENTATION: Following a routine catheter change by community nurses in a male person with tetraplegia, the catheter drained only a small amount of urine. Therefore, the patient attended the hospital where the staff removed the catheter but could not place a new catheter. The doctor tried different catheters and on fifth attempt, inserted a catheter. The patient continued to bypass urine and was prescribed Solifenacin. On self-referral to spinal unit, urethral trauma was suspected. CT of pelvis revealed the balloon of the Foley catheter in the penile urethra at penis base with the tip projecting beyond the penile shaft. Suprapubic cystostomy was done. The patient continued to leak urine from the penis; required penile sheath drainage and an additional leg bag. CLINICAL DISCUSSION: This case illustrates the value of CT of pelvis including the penis in detecting urethral trauma and misplacement of the catheter. Physicians should look for symptoms and signs of urethral trauma and incorrect positioning of the catheter. Imaging studies should be done without delay to assess urethral trauma and misplacement of urinary catheter. CONCLUSION: We use Urethrotech urethral catheterisation in patients in whom the first attempt to insert a catheter per urethra is unsuccessful, or in patients with a history of difficult catheterisation. This helped to minimise urethral trauma and achieve successful catheterisation.

Principles for Continuing Professional Development (CPD) Programs: A Statement by the ACPE CPD Advisory Committee.

Continuing Professional Development (CPD) has received increased attention within the pharmacy profession in the United States and is recognized as a potential pathway for ongoing professional development and practice transformation. Despite potential benefits of CPD, adoption in the United States has remained limited. A CPD program accreditation pathway, including principles, guidance, and a credit system for CPD programs, has recently been approved by the Accreditation Council for Pharmacy Education Board of Directors. This commentary reviews existing literature regarding pharmacy CPD, introduces CPD program principles and guidance for CPD program providers, and describes the model for awarding CPD units.

Milk of calcium in renal calyces, renal pelvis, and ureter in a person with tetraplegia.

Milk of calcium is a colloidal suspension of precipitated calcium salts which lies in a dependent manner and imaging reveals a horizontal upper edge. We report a 44-year-old male person with tetraplegia, who had been staying in bed for prolonged periods due to ischial and trochanteric pressure sores. Ultrasound scan of the kidneys revealed numerous variable-sized stones in the left kidney. CT of abdomen showed stones in the left kidney with dense layering of calcific material in a dependent distribution assuming the shape of the renal pelvis and the calyces. CT images in axial and corresponding sagittal views showed milk of calcium exhibiting a fluid level in the renal pelvis and calyces and the ureter. This is the first report of milk of calcium detected in the renal pelvis and calyces as well as in the ureter of a person with spinal cord injury. Following insertion of a ureteric stent, the milk of calcium in the ureter drained partly but the renal milk of calcium persisted. The renal stones were pulverized by ureteroscopy and LASER lithotripsy. Follow-up CT of kidneys performed 6 weeks after surgery showed the milk of calcium in the left ureter had drained, but there was no significant change of the left sizeable branching pelvi-calyceal stone regarding its extension and density.

On the need for metaphysics in psychedelic therapy and research.

The essential proposal of this text is that psychedelic-induced metaphysical experiences should be integrated and evaluated with recourse to metaphysics. It will be argued that there is a potential extra benefit to patients in psychedelic-assisted therapy if they are provided with an optional, additional, and intelligible schema and discussion of metaphysical options at the integrative phase of the therapy. This schema (the "Metaphysics Matrix") and a new Metaphysics Matrix Questionnaire ("MMQ") stemming therefrom will be presented, the latter of which can also be used as an alternative or additional tool for quantitative measurement of psychedelic experience in trials. Metaphysics is not mysticism, despite some overlap; and certainly not all psychedelic experience is metaphysical or mystical-all three terms will be defined and contrasted. Thereafter psychedelic therapy will be presented and analysed in order to reveal the missing place for metaphysics. Metaphysics, with epistemology (theory of knowledge) and axiology (ethics and aesthetics), is a defining branch of Philosophy. Metaphysics, in contrast to mysticism, is considered to be based on argument rather than pure revelation. Thus, in psychedelic-assisted psychotherapy one sees here the potential bridge between reason-based philosophy and practical therapy-or, more broadly, with psychedelic-assisted psychotherapy there is the potential and mutually beneficial fusion of philosophy with practical science.

Pandemic planning: data, information and evidence.

In this article, we examine the role and effectiveness of the Centers for Disease Control and Prevention in the USA and Europe and consider possible lessons for future pandemic planning in Australia. We also 'map' the interjurisdictional communication pathways that have been secured since the election of the new Commonwealth government. We suggest a number of steps that could be taken to upgrade the collection, distribution, accessibility and timelines of key information required to improve pandemic management and national health outcomes. While it may be hard to contemplate a move to a fully integrated National capacity when we are only just emerging from the pandemic, we do have a unique opportunity to at least start the process of review. We should use the lessons we have learned to transform our systems, rather than 'tinker' with them and ensure we are better prepared for next time.

Evaluating the Impact of a Pharmacist-Led Antimicrobial Stewardship Intervention at Discharge in a Community, Nonteaching Hospital.

INTRODUCTION: Approximately 30% to 50% of hospital discharge antimicrobials are inappropriate. Limited data exist on approaches to improve antimicrobial prescribing practices at the time of discharge from a community hospital. Objective: To assess the impact of a comprehensive pharmacist-led antimicrobial stewardship intervention at discharge. METHODS: We conducted a quasi-experimental, pre-post study. A biphasic intervention took place on 2 medicine units from November 2019 to May 2020 at a community hospital. Baseline data were collected, followed by prescriber education on antimicrobial stewardship to both units (education phase). Next, a pharmacist-led intervention took place on one unit (intervention phase). The primary outcome was composite appropriateness of an oral antimicrobial prescribed to an adult at the time of discharge, defined by narrow spectrum of activity, dosing, and duration of therapy. The primary outcome was assessed using Fisher exact test. RESULTS: Baseline composite appropriateness was 30% (n = 12) on the control unit and 30.8% (n = 20) on the intervention unit. From baseline to posteducation, no significant change in composite appropriateness was found on the control (30% to 26.7%, P = 0.256) or intervention (30.8% to 19.4%, P = 0.09) unit. There was no significant difference between the education to intervention phase (26.7% vs 35%, P = 0.254) on the control unit. On the intervention unit, a significant difference in composite appropriateness was found from the education to intervention phase (19.4% vs 47.8%, P = 0.017). CONCLUSION AND RELEVANCE: A pharmacist-led intervention improved appropriateness of oral antimicrobials prescribed at discharge. One-time education was insufficient for improving antimicrobial stewardship.

Value of serial ultrasound imaging in conservative management of epididymo-cutaneous fistula in a person with cervical spinal cord injury.

Epididymo-cutaneous fistula was seen in a person with cervical spinal cord injury and neuropathic bladder. This patient developed left epididymitis; then he formed an abscess superficial to the tail of the epididymis, which burst open to the skin discharging pus; subsequently, this progressed to epididymo-cutaneous fistula. A few drops of urine would leak through the fistula. The carers kept a dressing over the fistula to collect the small amount of urine leak and changed the dressing daily. This patient's carers squeezed any subcutaneous collection and drained the pus through the fistula. Serial ultrasound imaging of the scrotum was performed to guide the clinical management: (1) any subcutaneous abscess detected by the ultrasound scan was drained promptly; (2) ultrasound scans confirmed absence of any pathology in the testis; (3) the course of the disease was monitored as chronic epididymitis with echogenic debris in epididymal tail progressed to development of epididymo-cutaneous fistula and later to a chronic fistula with a matured tract. The serial scans revealed thickened tail of the left epididymis with heterogenous echo texture with no abscess formation, which encouraged the continuation of conservative management over a 5-year period while maintaining good quality of life. At the last follow-up in June 2022, leakage of urine from the epididymo-cutaneous fistula was observed very infrequently (once a month).

COVID-19 revisited – is a national pandemic plan possible?

As we review health governance during the COVID-19 pandemic, we have an opportunity to reflect on these processes and ensure that future challenges might be managed in a more collaborative and whole of system response. This 'Perspective' reviews COVID-19 responses in Australia, reflects on a number of potential solutions that have been developed by organisations over the past two decades and proffers a governance framework for a Communicable Disease and Pandemic Management Authority that might assist health responses to future challenges.

Large amounts of debris in the neuropathic bladder in persons with spinal cord injury; value of ultrasound scan in detection and management of vesical debris.

Persons with spinal cord injury are at risk for developing debris in the neuropathic bladder. Ultrasound scan of the urinary bladder helps to (1) detect debris, (2) differentiate debris from other bladder lesions, (3) alert the spinal cord physician to review bladder management, and (4) monitor the effect of various treatment regime to clear the debris. We present 4 cases to illustrate the sonographic appearances of debris in the neuropathic bladder and how treatment plans tailored to the needs of the individual patient helped to clear the debris.

Audiology, Medicine, and Pharmacy Interprofessional Preliminary Interviews and Discussions: Improving Hearing Health Care in Rural Alabama.

PURPOSE: Access and affordability of hearing health care varies depending on residency and individual financial means. Those living in rural areas have limited health care resources and experience higher levels of poverty compared to those living in urban regions. The purpose of this study was to determine the feasibility of interprofessional collaboration among physicians and audiologists and pharmacists and audiologists to improve access and affordability of hearing health care in rural communities. METHOD: Sixteen family physicians and medicine residents and 15 community pharmacists participated in the study. Physicians and residents completed an online survey to assess education regarding hearing health care and their understanding of hearing loss intervention. They also participated in small virtual focus group discussions. Pharmacists participated in virtual discussions based on guided questions. RESULTS: The discussions with both physicians and pharmacists highlighted the need for more education, resources, and awareness of the negative impact of hearing loss on overall quality of life. Comments from these discussions were placed within the socio-ecological model of health behavior to increase understanding of hearing health behavior. CONCLUSIONS: Increased collaboration among medical professionals has the potential to improve access to hearing health care for those living in audiologically underserved regions of the country. Further research will identify how to increase effective and sustainable hearing health care resources in rural communities.

Traumatic Imagination in Traditional Stories of Gender-Based Violence.

Traumatic imagination includes creative processes in which traumatic memories are transformed into narratives of suffering. This article emphasizes the importance of storytelling in victims' mental health and offers a literary perspective on how some women's experiences of suffering can be expressed in the telling of traditional stories, which confer some protection from stigma to individual women in Turkish and Afghan societies.