Post-transplant lymphoproliferative disorders following kidney transplantation: A literature review with updates on risk factors, prognostic indices, screening strategies, treatment and analysis of donor type.

Post-transplant lymphoproliferative disorders (PTLD) is a devastating complication of kidney transplantation with an insidious presentation and potential to disseminate aggressively. This review delineates the risk factors, prognostic indexes, screening, current management algorithm and promising treatment strategies for PTLD. Kidneys from both extended criteria donors (ECD) and living donors (LD) are being increasingly used to expand the donor pool. This review also delineates whether PTLD outcomes vary based on these donor sources. While Epstein-Barr virus (EBV) is a well-known risk factor for PTLD development, the use of T-cell depleting induction agents has been increasingly implicated in aggressive, monomorphic forms of PTLD. Research regarding maintenance therapy is sparse. The international prognostic index seems to be the most validate prognostic tool. Screening for PTLD is controversial, as annual PET-CT is most sensitive but costly, while targeted monitoring of EBV-seronegative patients was more economically feasible, is recommended by the American Society of Transplantation, but is limited to a subset of the population. Other screening strategies such as using Immunoglobulin/T-cell receptor require further validation. A risk-stratified approach is taken in the treatment of PTLD. The first step is the reduction of immunosuppressants, after which rituximab and chemotherapy may be introduced if unsuccessful. Some novel treatments have also shown potential benefit in studies: brentuximab vedotin, chimeric antigen receptor T-cell therapy and EBV-specific cytotoxic T lymphocytes. Analysis of LD v DD recipients show no significant difference in incidence and mortality of PTLD but did reveal a shortened time to development of PTLD from transplant. Analysis of SCD vs ECD recipients show a higher incidence of PTLD in the ECD group, which might be attributed to longer time on dialysis for these patients, age, and the pro-inflammatory nature of these organs. However, incidence of PTLD overall is still extremely low. Efforts should be focused on optimising recipients instead. Minimising the use of T-cell depleting therapy while encouraging research on the effect of new immunosuppressants on PTLD, screening for EBV status are essential, while enabling shared decision-making during counselling when choosing kidney donor types and individualised risk tailoring are strongly advocated.

The Clinical Course of Paranasal Sinus Mucocoeles-A Retrospective Case Series.

Paranasal sinus mucocoeles can be secondary to chronic rhinosinusitis and can result in intra-orbital and intra-cranial complications requiring surgical management. The natural history of conservatively managed mucocoeles is not well established. We aimed to quantify the proportion of radiologically identified paranasal sinus mucocoeles resulting in complications over 10 years. We retrospectively reviewed anonymised data on radiologically diagnosed mucocoeles between 2011 and 2021 at two UK hospitals. We collected data on age at presentation, extent of sinus involvement, management and complications. We identified 60 patients with mucocoeles, of which 35 (58%) were incidental findings from radiological investigations. The mean age was 58 years. Fifteen patients (25%) were managed surgically and one presented with recurrence following surgery. Overall, six patients (10%) had an intra-orbital extension of their mucocoele and three (5%) had an intra-cranial extension. There was no difference in the rates of intra-cranial extension between conservative and surgical cases but surgical cases included a higher rate of intra-orbital extensions (27% vs. 4%, p = 0.01). The proportion of patients requiring surgical intervention in this study is low. Incidental and asymptomatic mucocoeles have a relatively benign disease course and selected uncomplicated cases can be considered for conservative management with serial scanning at 12 months.

Effectiveness of topical gabapentin in the treatment of vulvodynia: a narrative synthesis.

Vulvodynia is a leading cause of dyspareunia in premenopausal women, causing considerable morbidity and sexual dysfunction. A multimodal approach is used to treat vulvodynia. Alongside psychosocial interventions and physiotherapy, pharmacological treatment such as oral gabapentin are used in the treatment of vulvodynia. Topical formulations of gabapentin have shown promise in animal models and case reports investigating its use in other pain conditions. The topical route also avoids the systemic complications of gabapentin such as somnolence, dizziness, and peripheral edema. This study aimed to perform a narrative synthesis of studies investigating the use of topical gabapentin in the treatment of vulvodynia. The primary outcome was a change in pain score following treatment with topical gabapentin. A broad literature search was performed, which identified four studies for inclusion. The included studies reported improved pain measures following treatment; however, conclusions cannot be made due to methodological heterogeneity and inherent limitations. These include lack of control arms, small sample sizes, lack of patient randomization, and use of combination treatments. Due to the paucity of evidence, this review supports the future implementation of double-blind randomized controlled trials to further investigate the efficacy of topical gabapentin in the treatment of vulvodynia.

An Updated Analysis of Clinical Outcome Measures Across Patients From the UK Medical Cannabis Registry.

Introduction: There is a growing body of literature supporting the efficacy of cannabis-based medicinal products (CBMPs). Despite an increase in prescribing globally, there is a paucity of high-quality clinical data on the efficacy of CBMPs for many conditions. This study aims to detail the changes in health-related quality of life (HRQoL) and associated clinical safety in patients prescribed CBMPs for any clinical indication from the UK Medical Cannabis Registry (UKMCR). Methods: An uncontrolled prospective case series of the UKMCR was analyzed. Primary outcomes included change from baseline in patient-reported outcome measures collected across all patients (the Generalized Anxiety Disorder Scale [GAD-7], EQ-5D-5L, and Sleep Quality Scale [SQS]) at 1, 3, and 6 months. Secondary outcomes included the self-reported incidence and severity of adverse events. Statistical significance was defined as p<0.050. Results: Three hundred twelve patients were included in the final analysis, with a mean age of 44.8. The most common primary diagnoses were chronic pain of undefined etiology (n=102, 32.7%), neuropathic pain (n=43, 13.8%), and fibromyalgia (n=31, 9.9%). Before enrolment, 112 (35.9%) patients consumed cannabis daily. The median cannabidiol and (-)-trans-Δ9-tetrahydrocannabinol doses prescribed at baseline were 20.0 mg (0.0-510.0 mg) and 3.0 mg (0.0-660.0 mg), respectively. Statistically significant improvements were observed in GAD-7, EQ-5D-5L Index, EQ-5D Visual Analog Scale and SQS scores at 1, 3, and 6 months (p<0.050). There were 94 (30.1%) reported adverse events, of which nausea (n=12, 3.8%), dry mouth (n=10, 3.2%), dizziness (n=7, 2.2%), and somnolence (n=7, 2.2%) were the most common. Conclusion: This study demonstrated CBMP treatment to be associated with a relatively low incidence of severe adverse events in the medium-term. Positive changes following treatment were observed in general, as well as anxiety and sleep-specific, HRQoL outcomes. Randomized controlled trials are still awaited to assess causation; however, real-world evidence can help inform current clinical practice, future trials, and is an important component of pharmacovigilance.

UK Medical Cannabis Registry: an analysis of clinical outcomes of medicinal cannabis therapy for generalized anxiety disorder.

OBJECTIVES: Anxiety disorders are one of the most common reasons for seeking treatment with cannabis-based medicinal products (CBMPs). Current pharmacological treatments are variable in efficacy and the endocannabinoid system has been identified as a potential therapeutic target. This study aims to detail the changes in health-related quality-of-life (HRQoL) and clinical safety following CBMP therapy for generalized anxiety disorder. METHODS: A case series from the UK Medical Cannabis Registry was performed. Primary outcomes included changes from baseline in patient-reported outcome measures (the General Anxiety Disorder Scale (GAD-7), EQ-5D-5L (a measure of health-related quality of life), and Sleep Quality Scale (SQS)) at 1, 3 and 6 months. Statistical significance was defined as p<0.050. RESULTS: Sixty-seven patients were treated for generalized anxiety disorder. Statistically significant improvements were observed in GAD-7, EQ-5D-5L Index Value, EQ5D Visual Analog Scale, and SQS scores at 1, 3 and 6 months (p<0.050). Twenty-five (39.1%) patients reported adverse events during the follow-up period. CONCLUSION: This study suggests that CBMPs may be associated with improvements in HRQoL outcomes when used as a treatment for generalized anxiety disorder. These findings must be treated with caution considering limitations of study design; however this data may help inform future clinical studies and practice.Plain Language SummaryAnxiety disorders are the most prevalent psychiatric illness type in the United Kingdom, with 8.2 million cases reported in 2010. Generalized anxiety disorder (GAD), the most common anxiety disorder, debilitates, and so reduces the quality of life of those who suffer from the condition.The efficacy of current treatments for GAD varies greatly from person-to-person. The endocannabinoid system in the human body is currently attracting a lot of attention in the scientific community as it can be targeted by chemicals in the cannabis plant to produce therapeutic effects in order to treat GAD. There is, however, a lack of studies investigating the effects of medicinal cannabis in GAD, and so this study aims to explore the drug's effect on quality of life in patients suffering from GAD.Sixty-seven patients who attended the Sapphire Clinics for medicinal cannabis treatment for GAD were included in the study. The results from this study highlight that medicinal cannabis may improve generalized anxiety disorder, general health-related quality of life, and sleep-specific outcomes at 1, 3, and 6 months after starting treatment. There was also a low number of severe, disabling, and life-threatening adverse events experienced by patients. Although this study explores the effects of medicinal cannabis in a real clinical setting, the results were not compared to other types of treatment. Future studies with a comparator are therefore needed before concluding the true effects of medicinal cannabis in patients with GAD.

UK Medical Cannabis registry: an analysis of clinical outcomes of medicinal cannabis therapy for chronic pain conditions.

OBJECTIVES: To explore pain-specific, general health-related quality of life (HRQoL), and safety outcomes of chronic pain patients prescribed cannabis-based medicinal products (CBMPs). METHODS: A case series was performed using patients with chronic pain from the UK Medical Cannabis Registry. Primary outcomes were changes in Brief Pain Inventory short-form (BPI), Short-form McGill Pain Questionnaire-2 (SF-MPQ-2), Visual Analogue Scale-Pain (VAS), General Anxiety Disorder-7 (GAD-7), Sleep Quality Scale (SQS), and EQ-5D-5L, at 1, 3, and 6 months from baseline. Statistical significance was defined at p-value<0.050. RESULTS: 190 patients were included. Median initial Δ9-tetrahydrocannabinol and cannabidiol daily doses were 2.0mg (range:0.0-442.0mg) and 20.0mg (range:0.0-188.0mg) respectively. Significant improvements were observed within BPI, SF-MPQ-2, GAD-7, SQS, EQ-5D-5 L index, and VAS measures at all timepoints (p<0.050). Seventy-five adverse events (39.47%) were reported, of which 37 (19.47%) were rated as mild, 23 (12.11%) as moderate, and 14 (7.37%) as severe. Nausea (n=11; 5.8%) was the most frequent adverse event. CONCLUSION: An association was identified between patients with chronic pain prescribed CBMPs and improvements in pain-specific and general HRQoL outcomes. Most adverse events were mild to moderate in severity, indicating CBMPs were well tolerated. Inherent limitations of study design limit its overall applicability.

UK Medical Cannabis Registry palliative care patients cohort: initial experience and outcomes.

INTRODUCTION: Palliative care aims to improve quality of life through optimal symptom control and pain management. Cannabis-based medicinal products (CBMPs) have a proven role in the treatment of chemotherapy-induced nausea and vomiting. However, there is a paucity of high-quality evidence with regards to the optimal therapeutic regimen, safety, and effectiveness of CBMPs in palliative care, as existing clinical trials are limited by methodological heterogeneity. The aim of this study is to summarise the outcomes of the initial subgroup of patients from the UK Medical Cannabis Registry who were prescribed CBMPs for a primary indication of palliative care, cancer pain and chemotherapy-induced nausea and vomiting, including effects on health-related quality of life and clinical safety. METHODS: A case series from the UK Medical Cannabis Registry of patients, who were receiving CBMPs for the indication of palliative care was undertaken. The primary outcome consisted of changes in patient-reported outcome measures including EQ-5D-5L, General Anxiety Disorder-7 (GAD-7), Single-Item Sleep Quality Scale (SQS), Pain Visual Analog Scale (VAS) and the Australia-Modified Karnofsky Performance Scale at 1 and 3 months compared to baseline. Secondary outcomes included the incidence and characteristics of adverse events. Statistical significance was defined by p-value< 0.050. RESULTS: Sixteen patients were included in the analysis, with a mean age of 63.25 years. Patients were predominantly prescribed CBMPs for cancer-related palliative care (n = 15, 94%). The median initial CBD and THC daily doses were 32.0 mg (Range: 20.0-384.0 mg) and 1.3 mg (Range: 1.0-16.0 mg) respectively. Improvements in patient reported health outcomes were observed according to SQS, EQ-5D-5L mobility, pain and discomfort, and anxiety and depression subdomains, EQ-5D-5L index, EQ-VAS and Pain VAS validated scales at both 1-month and 3-months, however, the changes were not statistically significant. Three adverse events (18.75%) were reported, all of which were either mild or moderate in severity. CONCLUSION: This small study provides an exploratory analysis of the role of CBMPs in palliative care in the first cohort of patients since CBMPs legalisation in the UK. CBMPs were tolerated with few adverse events, all of which were mild or moderate and resolved spontaneously. Further long-term safety and efficacy studies involving larger cohorts are needed to establish CBMPs role in palliative care, including comparisons with standard treatments.