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New Therapeutic Horizons in Chronic Kidney Disease: The Role of SGLT2 Inhibitors in Clinical Practice.
No full textChronic kidney disease (CKD) is a serious, progressive condition associated with significant patient morbidity. Hypertension control and use of renin-angiotensin system blockers are the cornerstones of treatment for CKD. However, even with these treatment strategies, many individuals will progress towards kidney failure. Recently, sodium-glucose cotransporter 2 (SGLT2) inhibitor clinical trials with primary renal endpoints have firmly established SGLT2 inhibition, in addition to standard of care, as an effective strategy to slow down the progression of CKD and reduce some of its associated complications. The emergence of this new clinical evidence supports the use of SGLT2 inhibitors in the management of CKD in people with and without diabetes. As licensing and guidelines for SGLT2 inhibitors are updated, there is a need to adapt CKD treatment pathways and for this class of drugs to be included as part of standard care for CKD management. In this article, we have used consensus opinion alongside the available evidence to provide support for the healthcare community involved in CKD management, regarding the role of SGLT2 inhibitors in clinical practice. By highlighting appropriate prescribing and practical considerations, we aim to encourage greater and safe use of SGLT2 inhibitors for people with CKD, both with and without diabetes
Comparison of transverse versus longitudinal skin incisions for femoral endarterectomy and patchplasty.
No full textINTRODUCTION
Access to the femoral artery for a femoral endarterectomy and patchplasty (CFE) can be undertaken either through transverse (TI) or longitudinal incision (LI). LIs have been shown in previous studies to have higher groin complications though these were undertaken in multiple types of vascular procedures. We looked at wound complications for patients undergoing elective CFE procedures only with or without angioplasty via TI or LI.
METHODS
All patients who had undergone CFE were retrospectively analysed from a prospective database. Length of stay, wound complications and readmission rates were recorded. Factors for wound complication were looked at using logistic regression with backward elimination.
RESULTS
122 CFE procedures were performed (30 TI) over the study period. 92 (76.7%) of patients had a prosthetic patch used, whilst 57 (46.7%) patients underwent an adjunctive endovascular procedure, namely, iliac angioplasty and stenting. Median length of stay was 3 days for both groups. The wound complication rate was 6.7% in the TI group and 22.6% in the LI group. 85.6% of the wound complications were identified after discharge. 6/122 (4.9%) were readmitted for intravenous antibiotics, whilst others were managed in the outpatient setting. TI (aOR = 0.15; 95% 0.03-0.75) and combined open FE with endovascular revascularisation (aOR = 0.33; 95% 0.11-0.95) had protective effects on wound complications. Type of the patch used was not associated with any wound complications ( = 0.07).
CONCLUSION
Compared to traditional LI, TI for CFE and OTA have lower risk of wound complications and reduced readmission rates in our series. We advocate adopting TI as the standard for femoral artery procedures rather than LI
Widening the net: a literature review of antimicrobial agents with potential suitability for outpatient parenteral antimicrobial therapy services-the importance of storage and stability.
No full textOBJECTIVES
Outpatient parenteral antimicrobial therapy (OPAT) services using continuous infusions (CIs) of antimicrobial agents in elastomeric devices require evidence of acceptable stability of the agent over the infusion period. A period of refrigerated storage of filled devices, followed by the CI period, is useful for OPAT services but can present a significant challenge to the stability of drugs. The aims of this study were to review fresh-filled stability data on antimicrobials which would be useful for OPAT services and to identify suitable candidates for further assessment.
METHODS
Searches identified papers relating to stability assessments of antimicrobials for immediate use tested above 31°C using a stability-indicating method.
RESULTS
We identified 18 stability studies published in 12 papers between 2015 and 2020, assessing the stability of 10 agents. Aminopenicillins like ampicillin and amoxicillin appear too unstable for CI, while benzylpenicillin may benefit from buffering to improve its stability. Cephalosporins vary in their stability and CI periods of 24 hours may not be achievable. Of the carbapenems, there are insufficient data for doripenem but meropenem has been extensively studied and is unsuitable for CI longer than 6 hours. Voriconazole may be suitable for CI but needs further investigation.
CONCLUSIONS
Some drugs identified in our review are unlikely to be suitable for continuous infusion in OPAT services due to instability. Using a 'fresh-fill' approach, without refrigerated storage, may make some drugs useful while other agents should be considered for further assessment to Yellow Cover Document standards. The impact of buffering for penicillins should be assessed further
Craniopharyngiomas.
No full textCraniopharyngiomas are rare epithelial tumours situated primarily in the sellar/parasellar region, occurring along the path of the craniopharyngeal duct. Whilst classed as histologically benign tumours, their unpredictable growth pattern and proximity to vital structures including the optic chiasm, hypothalamus, and pituitary gland renders them a considerable threat, with significant associated morbidity and increase in mortality. Occurring both in child and adulthood, their clinical manifestations are broad, commonly with symptoms/signs secondary to hypothalamic-pituitary dysfunction, raised intracranial pressure and visual compromise. They have two distinct histological subtypes (adamantinomatous and papillary), with unique patterns of age distribution, and genetic and molecular make-up. With increasing understanding of their genetic pathogenesis including BRAF V600E mutations in the papillary subtype, and β-catenin mutations in the adamantinomatous, further research provides hope for the discovery of targeted medical therapy that can exploit molecular changes occurring as a result of such alterations. Until then, primary treatment consists of surgery with or without radiotherapy, with intracystic aspiration, chemotherapy or irradiation being alternative options in selected patients. Long term management by an experienced multidisciplinary team is essential, given the breadth of complications, including hypothalamic morbidity, visual compromise, cognitive and neuropsychological sequelae and impairment to quality of life
Dual-energy computed tomography: Survey results on current uses and barriers to further implementation.
No full textOBJECTIVE
To gauge the current availability of dual-energy computed tomography (DECT) scanners in the UK, establish available technologies, look broadly at current clinical uses in adults and paediatrics, and identify barriers to implementation and potential ways to increase use.
METHODS
A survey was distributed amongst 10 radiology departments and shared on two national professional co-operation mail bases; the survey ran from 20th July to 9th December 2020. It explored current DECT utilisation in adults and paediatrics as well as barriers to use and suggestions to overcome those barriers.
RESULTS
The survey demonstrated DECT availability on 39 (40%) of the 98 CT scanners, but there was limited clinical use in adults and paediatrics. Eighteen (72%) of the 25 respondents had access to at least one DECT scanner, with 14 (56%) having adult DECT protocols in clinical use; <10% head examinations and <50% for other anatomical areas. Only two (8%) respondents had DECT paediatric protocols in clinical use; <10% examinations for all anatomical areas.The main barriers to implementation identified were lack of experience with DECT (8 (44%) users (adult) and 10 (56%) users (paediatric)) and no clinical protocols available (6 (33%) users (adult and paediatric)).Understanding DECT benefits and establishing suitable protocols were the most popular suggestions for increased implementation (10 (40%) of 25 respondents).
CONCLUSION
DECT scanners are available, but clinical use is limited for both adults and paediatrics. The main barriers identified were lack of experience with DECT and the availability of suitable protocols. Further work identified to help implementation included better education on the benefits of DECT, provision of clinical protocols and ensuring a multidisciplinary approach.
ADVANCES IN KNOWLEDGE
Barriers to implementation of clinical DECT protocols were identified, together with potential solutions to overcome these and enable further implementation
Increased risk of COVID-19-related admissions in patients with active solid organ cancer in the West Midlands region of the UK: a retrospective cohort study.
No full textOBJECTIVE
Susceptibility of patients with cancer to COVID-19 pneumonitis has been variable. We aim to quantify the risk of hospitalisation in patients with active cancer and use a machine learning algorithm (MLA) and traditional statistics to predict clinical outcomes and mortality.
DESIGN
Retrospective cohort study.
SETTING
A single UK district general hospital.
PARTICIPANTS
Data on total hospital admissions between March 2018 and June 2020, all active cancer diagnoses between March 2019 and June 2020 and clinical parameters of COVID-19-positive admissions between March 2020 and June 2020 were collected. 526 COVID-19 admissions without an active cancer diagnosis were compared with 87 COVID-19 admissions with an active cancer diagnosis.
PRIMARY AND SECONDARY OUTCOME MEASURES
30-day and 90-day post-COVID-19 survival.
RESULTS
In total, 613 patients were enrolled with male to female ratio of 1:6 and median age of 77 years. The estimated infection rate of COVID-19 was 87 of 22 729 (0.4%) in the patients with cancer and 526 of 404 379 (0.1%) in the population without cancer (OR of being hospitalised with COVID-19 if having cancer is 2.942671 (95% CI: 2.344522 to 3.693425); p<0.001). Survival was reduced in patients with cancer with COVID-19 at 90 days. R-Studio software determined the association between cancer status, COVID-19 and 90-day survival against variables using MLA. Multivariate analysis showed increases in age (OR 1.039 (95% CI: 1.020 to 1.057), p<0.001), urea (OR 1.005 (95% CI: 1.002 to 1.007), p<0.001) and C reactive protein (CRP) (OR 1.065 (95% CI: 1.016 to 1.116), p<0.008) are associated with greater 30-day and 90-day mortality. The MLA model examined the contribution of predictive variables for 90-day survival (area under the curve: 0.749); with transplant patients, age, male gender and diabetes mellitus being predictors of greater mortality.
CONCLUSIONS
Active cancer diagnosis has a threefold increase in risk of hospitalisation with COVID-19. Increased age, urea and CRP predict mortality in patients with cancer. MLA complements traditional statistical analysis in identifying prognostic variables for outcomes of COVID-19 infection in patients with cancer. This study provides proof of concept for MLA in risk prediction for COVID-19 in patients with cancer and should inform a redesign of cancer services to ensure safe delivery of cancer care
Evaluation of the mechanisms of sarcopenia in chronic inflammatory disease: protocol for a prospective cohort study.
No full textBACKGROUND
Several chronic inflammatory diseases co-exist with and accelerate sarcopenia (reduction in muscle strength, function and mass) and negatively impact on both morbidity and mortality. There is currently limited research on the extent of sarcopenia in such conditions, how to accurately assess it and whether there are generic or disease-specific mechanisms driving sarcopenia. Therefore, this study aims to identify potential mechanisms driving sarcopenia within chronic inflammatory disease via a multi-modal approach; in an attempt to help define potential interventions for future use.
METHODS
This prospective cohort study will consist of a multi-modal assessment of sarcopenia and its underlying mechanisms. Recruitment will target three chronic inflammatory diseases: chronic liver disease (CLD) (n=50), with a subset of NAFLD (n=20), inflammatory bowel disease (IBD) (n=50) and rheumatoid arthritis (RA) (n=50) both before and after therapeutic intervention. In addition, 20 age and sex matched healthy individuals will be recruited for comparison. Participants will undergo 4 assessment visits at weeks 0, 2, 12 and 24. Visits will consist of the following assessments: blood tests, anthropometrics, functional assessment, quadriceps muscle imaging, actigraphy, quality of life questionnaires, food diary collection and muscle biopsy of the vastus lateralis (at weeks 2 and 24 only). In addition, stool and urine samples will be collected for future microbiome and metabolomics analysis.
DISCUSSION
This is the first study to use a multi-modal assessment model to phenotype sarcopenia in these chronic inflammatory diseases. We hope to identify generic as well as disease-specific mechanisms driving sarcopenia. We appreciate that these cohorts do require separate standards of care treatments which limit comparison between groups.
ETHICS AND DISSEMINATION
The study is approved by the Health Research Authority - West Midlands Solihull Research Ethics Service Committee Authority (REC reference: 18/WM/0167). Recruitment commenced in January 2019 and will continue until July 2021. The study was halted in March 2020 and again in January 2021 with the COVID-19 pandemic. The findings will be disseminated through peer-reviewed publications and conference presentations. All data will be stored on a secure server.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT04734496
Emerging drugs for the treatment of primary sclerosing cholangitis.
No full textPrimary sclerosing cholangitis (PSC) is a rare immune-mediated cholestatic disease for which no medical therapy has been shown to slow disease progression. Consequently, liver transplantation is the only lifesaving intervention for patients, and despite being a rare disease, PSC is the lead indication for transplantation across several European countries. The vast majority of patients (>70%) also develop inflammatory bowel disease (IBD) at some point in their lifetime, which imparts added lifetime risks of hepatobiliary malignancy and colorectal cancer. The rare disease nature, variable and often slow rates of disease progression (years rather than months), and lack of robust surrogate biomarkers for early stage yet high risk disease, represent critical challenges in trial design that have long precluded the development of effective medical treatment. However, the horizon for new treatments is encouraging, given innovative clinical trial programmes led by industry, alongside several investigator-initiated studies. Herein, we outline the current platform of interventional trials in PSC, before discussing emerging areas of therapeutic interest
Clonal Evolution of High-Risk Chronic Lymphocytic Leukemia: A Contemporary Perspective.
No full textClonal evolution represents the natural process through which cancer cells continuously search for phenotypic advantages that enable them to develop and expand within microenvironmental constraints. In chronic lymphocytic leukemia (CLL), clonal evolution underpins leukemic progression and therapeutic resistance, with differences in clonal evolutionary dynamics accounting for its characteristically diverse clinical course. The past few years have witnessed profound changes in our understanding of CLL clonal evolution, facilitated by a maturing definition of high-risk CLL and an increasing sophistication of next-generation sequencing technology. In this review, we offer a modern perspective on clonal evolution of high-risk CLL, highlighting recent discoveries, paradigm shifts and unresolved questions. We appraise recent advances in our understanding of the molecular basis of CLL clonal evolution, focusing on the genetic and non-genetic sources of intratumoral heterogeneity, as well as tumor-immune dynamics. We review the technological innovations, particularly in single-cell technology, which have fostered these advances and represent essential tools for future discoveries. In addition, we discuss clonal evolution within several contexts of particular relevance to contemporary clinical practice, including the settings of therapeutic resistance to CLL targeted therapy and immunotherapy, as well as Richter transformation of CLL to high-grade lymphoma