Adult Cerebral Malaria: Acute and Subacute Imaging Findings, Long-term Clinical Consequences.

Cerebral malaria is an important cause of mortality and neurodisability in endemic regions. We show magnetic resonance imaging (MRI) features suggestive of cytotoxic and vasogenic cerebral edema followed by microhemorrhages in 2 adult UK cases, comparing them with an Indian cohort. Long-term follow-up images correlate ongoing changes with residual functional impairment.

The information required by people with inflammatory arthritis when taking Methotrexate: a mixed-methods systematic review.

OBJECTIVES: This mixed-methods systematic review aimed to identify and synthesize knowledge of the characteristics, content, and preferred format of information to support people with inflammatory arthritis (IA) to take MTX. METHODS: A literature search using MEDLINE, The Cochrane Library, EMBASE, CINAHL, PsychInfo, GreyEU, Web of Science and Open Dissertation was conducted to identify all studies published from 2000 to December 2022. Included studies detailed factors related to MTX information needs of people aged ≥18 years with IA published in English. The Joanna Briggs Institute Guidelines (JBI) for convergent integrated mixed-methods systematic reviews were followed using validated tools for data extraction and quality. The data was analysed using reflexive thematic analysis. RESULTS: Thirteen studies (seven quantitative, two mixed-methods and four qualitative) were included, involving 3425 adults, mainly female n = 2434 (71%), age 20-84 years. An overarching theme of a requirement for person-centred care was developed, with three interlinking themes: (1) accepting the need for treatment with MTX, (2) concerns about taking MTX, and (3) a need for tailored information and support. Limitations of the evidence included the use of heterogeneous outcome measures and instruments for measuring information needs. CONCLUSION: People with IA have individual, multifaceted information and support needs about MTX that are often unresolved when a one-size-fits-all approach is used. The findings of this review can inform rheumatology training to support a person-centred approach to identifying and addressing the specific needs and concerns and development of consistent easy-to-understand accessible MTX information.

Evaluating the use of reflective cafés in Specialist Community Practitioner and Specialist Community Public Health Nurse programmes.

Background: Specialist Community Practitioner (SCP) and Specialist Community Public Health Nurse (SCPHN) students are required to evidence their competency by the use of reflective practice as part of the NMC proficiencies. A reflective café trilogy comprising of three reflective teaching sessions was developed and introduced into a university programme to support and encourage alternative methods for deeper reflection within this student group. Aim: It was important for educators to evaluate if a reflective café met the student's needs and understand the usefulness of a 'reflective café' as a technique to support the process of reflecting on practice. Methods: Evaluation was undertaken using an online questionnaire. Findings: Students evaluated if the reflective café was useful for their own development and identified that the number of sessions met their developmental needs. Conclusion: The potential to develop alternative methods to reflect was recognised and the team plan to develop other reflective processes to support students in the future.

Community transmission of monkeypox in the United Kingdom, April to May 2022.

Between 7 and 25 May, 86 monkeypox cases were confirmed in the United Kingdom (UK). Only one case is known to have travelled to a monkeypox virus (MPXV) endemic country. Seventy-nine cases with information were male and 66 reported being gay, bisexual, or other men who have sex with men. This is the first reported sustained MPXV transmission in the UK, with human-to-human transmission through close contacts, including in sexual networks. Improving case ascertainment and onward-transmission preventive measures are ongoing.

Clinical and Economic Impact of Implementing OVIVA Criteria on Patients With Bone and Joint Infections in Outpatient Parenteral Antimicrobial Therapy.

The OVIVA study demonstrated noninferiority for managing bone and joint infections (BJIs) with oral antibiotics. We report that 79.7% of OPAT patients being treated for BJIs at our center would be eligible for oral antibiotics, saving a median (IQR) 19.5 IV-antibiotic days (8.5-37) and GBP 1234 (569-2594) per patient.

Intravenous catheter-related adverse events exceed drug-related adverse events in outpatient parenteral antimicrobial therapy.

BACKGROUND: Drug-related adverse events (AEs) are reported to be common amongst patients receiving outpatient parenteral antimicrobial therapy (OPAT). However, comparative data regarding intravenous (iv) catheter-related AEs are lacking. OBJECTIVES: To compare drug- and iv catheter-related AEs from a large UK OPAT centre. PATIENTS AND METHODS: We reviewed 544 OPAT episodes [median (IQR) age: 57 (39-71) years, 60% male, 13% with diabetes] with a median (IQR) duration of 7 (2-18) days. Clinically significant drug- and iv catheter-related AEs were calculated as a percentage of OPAT episodes with an AE and also as AEs per 1000 iv drug/catheter days. RESULTS: Drug-related AEs complicated 13 (2.4%) OPAT episodes at 1.7 (95% CI 0.9-2.9) per 1000 drug days. Catheter-related AEs occurred more frequently, complicating 32 (5.9%) episodes at 5.7 (95% CI 4.2-7.9) per 1000 iv catheter days (χ2 test for difference in AE rate: P < 0.001). Non-radiologically guided midline catheters were associated with the most frequent AEs (n = 23) at 15.6 (95% CI 10.3-23.4) per 1000 iv catheter days compared with other types of iv catheters (HR 8.4, 95% CI 2.4-51.9, P < 0.004), and self-administration was associated with a higher rate of catheter-related AEs at 12.0 (95% CI 6.0-23.9) per 1000 iv catheter days (HR 4.15, 95% CI 1.7-9.1, P = 0.007). CONCLUSIONS: Clinically significant iv catheter-related AEs occurred more frequently than drug-related AEs, especially when using non-radiologically guided midline catheters. Regular review of the need for iv therapy and switching to oral antimicrobials when appropriate is likely to minimize OPAT-related AEs.

Glucocorticoid induced adrenal insufficiency is common in steroid treated glomerular diseases - proposed strategy for screening and management.

BACKGROUND: Glucocorticoids (GCs) are frequently used to treat glomerular diseases but are associated with multiple adverse effects including hypothalamic-pituitary-adrenal axis inhibition that can lead to adrenal insufficiency (AI) on withdrawal. There is no agreed GC tapering strategy to minimise this risk. METHODS: This is a single centre retrospective study, between 2013 to 2016, of patients with glomerular disease on GC therapy for more than 3 months screened for GC induced AI with short synacthen stimulation tests (SSTs) done prior to complete GC withdrawal. We investigated the prevalence of AI, predictors, choice of screening tool and recovery. RESULTS: Biochemical evidence of GC induced AI was found in 57 (46.3%) patients. Total duration of GC did not differ between those with and without AI (p = 0.711). Patients with GC induced AI had a significantly lower pre-synacthen baseline cortisol as compared to patients without AI. A cut off pre-synacthen baseline cortisol of ≥223.5 nmol/l had a specificity of 100% for identifying individuals without biochemical AI. Patients with GC induced AI took a mean of 8.7 ± 4.6 months (mean ± SD) to recover. Patients with persistent AI had a significantly lower index post-synacthen cortisol measurement. CONCLUSIONS: We demonstrate that biochemically proven GC induced AI is common in patients with glomerular diseases, is not predicted by daily dose or duration and takes a considerable time to recover. The study supports the use of morning basal cortisol testing as an appropriate means to avoid the need for SSTs in all patients and should be performed in all patients prior to consideration of GC withdrawal after 3 months duration.

Propofol Alters Long Non-Coding RNA Profiles in the Neonatal Mouse Hippocampus: Implication of Novel Mechanisms in Anesthetic-Induced Developmental Neurotoxicity.

BACKGROUND: Propofol induces acute neurotoxicity (e.g., neuroapoptosis) followed by impairment of long-term memory and learning in animals. However, underlying mechanisms remain largely unknown. Long non-coding RNAs (lncRNAs) are found to participate in various pathological processes. We hypothesized that lncRNA profile and the associated signaling pathways were altered, and these changes might be related to the neurotoxicity observed in the neonatal mouse hippocampus following propofol exposure. METHODS: In this laboratory experiment, 7-day-old mice were exposed to a subanesthetic dose of propofol for 3 hours, with 4 animals per group. Hippocampal tissues were harvested 3 hours after propofol administration. Neuroapoptosis was analyzed based on caspase 3 activity using a colorimetric assay. A microarray was performed to investigate the profiles of 35,923 lncRNAs and 24,881 messenger RNAs (mRNAs). Representative differentially expressed lncRNAs and mRNAs were validated using reverse transcription quantitative polymerase chain reaction. All mRNAs dysregulated by propofol and the 50 top-ranked, significantly dysregulated lncRNAs were subject to bioinformatics analysis for exploring the potential mechanisms and signaling network of propofol-induced neurotoxicity. RESULTS: Propofol induced neuroapoptosis in the hippocampus, with differential expression of 159 lncRNAs and 100 mRNAs (fold change ± 2.0, P< 0.05). Bioinformatics analysis demonstrated that these lncRNAs and their associated mRNAs might participate in neurodegenerative pathways (e.g., calcium handling, apoptosis, autophagy, and synaptogenesis). CONCLUSION: This novel report emphasizes that propofol alters profiles of lncRNAs, mRNAs, and their cooperative signaling network, which provides novel insights into molecular mechanisms of anesthetic-induced developmental neurodegeneration and preventive targets against the neurotoxicity.

Insufficient Astrocyte-Derived Brain-Derived Neurotrophic Factor Contributes to Propofol-Induced Neuron Death Through Akt/Glycogen Synthase Kinase 3ß/Mitochondrial Fission Pathway.

BACKGROUND: Growing animal evidence demonstrates that prolonged exposure to propofol during brain development induces widespread neuronal cell death, but there is little information on the role of astrocytes. Astrocytes can release neurotrophic growth factors such as brain-derived neurotrophic factor (BDNF), which can exert the protective effect on neurons in paracrine fashion. We hypothesize that during propofol anesthesia, BDNF released from developing astrocytes may not be sufficient to prevent propofol-induced neurotoxicity. METHODS: Hippocampal astrocytes and neurons isolated from neonatal Sprague Dawley rats were exposed to propofol at a clinically relevant dose of 30 µM or dimethyl sulfoxide as control for 6 hours. Propofol-induced cell death was determined by propidium iodide (PI) staining in astrocyte-alone cultures, neuron-alone cultures, or cocultures containing either low or high density of astrocytes (1:9 or 1:1 ratio of astrocytes to neurons ratio [ANR], respectively). The astrocyte-conditioned medium was collected 12 hours after propofol exposure and measured by protein array assay. BDNF concentration in astrocyte-conditioned medium was quantified using enzyme-linked immunosorbent assay. Neuron-alone cultures were treated with BDNF, tyrosine receptor kinase B inhibitor cyclotraxin-B, glycogen synthase kinase 3ß (GSK3ß) inhibitor CHIR99021, or mitochondrial fission inhibitor Mdivi-1 before propofol exposure. Western blot was performed for quantification of the level of protein kinase B and GSK3ß. Mitochondrial shape was visualized through translocase of the outer membrane 20 staining. RESULTS: Propofol increased cell death in neurons by 1.8-fold (% of PI-positive cells [PI%] = 18.6; 95% confidence interval [CI], 15.2-21.9, P < .05) but did not influence astrocyte viability. The neuronal death was attenuated by a high ANR (1:1 cocultures; fold change [FC] = 1.17, 95% CI, 0.96-1.38, P < .05), but not with a low ANR [1:9 cocultures; FC = 1.87, 95% CI, 1.48-2.26, P > .05]). Astrocytes secreted BDNF in a cell density-dependent way and propofol decreased BDNF secretion from astrocytes. Administration of BDNF, CHIR99021, or Mdivi-1 significantly attenuated the propofol-induced neuronal death and aberrant mitochondria in neuron-alone cultures (FC = 0.8, 95% CI, 0.62-0.98; FC = 1.22, 95% CI, 1.11-1.32; FC = 1.35, 95% CI, 1.16-1.54, respectively, P < .05) and the cocultures with a low ANR (1:9; FC = 0.85, 95% CI, 0.74-0.97; FC = 1.08, 95% CI, 0.84-1.32; FC = 1.25, 95% CI, 1.1-1.39, respectively, P < .05). Blocking BDNF receptor or protein kinase B activity abolished astrocyte-induced neuroprotection in the cocultures with a high ANR (1:1). CONCLUSIONS: Astrocytes attenuate propofol-induced neurotoxicity through BDNF-mediated cell survival pathway suggesting multiple neuroprotective strategies such as administration of BDNF, astrocyte-conditioned medium, decreasing mitochondrial fission, or inhibition of GSK3ß.

Immunosuppressant-Related Lower Eyelid Edema in Transplant Patients.

Solid organ transplantation is the preferred method of treatment for a number of advanced medical conditions, but it requires systemic immunosuppression to prevent transplant rejection. The authors report 2 unique cases of persistent eyelid edema following solid organ transplantation believed to be related to their systemic immunosuppression. The eyelid findings developed after initiation of the immunosuppressant sirolimus. In 1 patient, the eyelid edema has persisted despite discontinuation of the medication. In the second patient, the immunosuppression could not be altered; therefore, he underwent surgical excision of the edematous lower eyelid. Sirolimus associated eyelid edema is an important medication side effect for ophthalmic and eyelid specialists to consider when a patient with a history of organ transplantation presents with localized noninflamed eyelid edema. This edema can persist despite discontinuation of the medication. Surgical excision of the edematous eyelid can achieve good results.

Recent Insights Into Molecular Mechanisms of Propofol-Induced Developmental Neurotoxicity: Implications for the Protective Strategies.

Mounting evidence has demonstrated that general anesthetics could induce developmental neurotoxicity, including acute widespread neuronal cell death, followed by long-term memory and learning abnormalities. Propofol is a commonly used intravenous anesthetic agent for the induction and maintenance of anesthesia and procedural and critical care sedation in children. Compared with other anesthetic drugs, little information is available on its potential contributions to neurotoxicity. Growing evidence from multiple experimental models showed a similar neurotoxic effect of propofol as observed in other anesthetic drugs, raising serious concerns regarding pediatric propofol anesthesia. The aim of this review is to summarize the current findings of propofol-induced developmental neurotoxicity. We first present the evidence of neurotoxicity from animal models, animal cell culture, and human stem cell-derived neuron culture studies. We then discuss the mechanism of propofol-induced developmental neurotoxicity, such as increased cell death in neurons and oligodendrocytes, dysregulation of neurogenesis, abnormal dendritic development, and decreases in neurotrophic factor expression. Recent findings of complex mechanisms of propofol action, including alterations in microRNAs and mitochondrial fission, are discussed as well. An understanding of the toxic effect of propofol and the underlying mechanisms may help to develop effective novel protective or therapeutic strategies for avoiding the neurotoxicity in the developing human brain.

Risk Factors and Best Practices for the Prevention of Post-Cardiac Surgery Surgical Site Infections in a Tertiary Care Centre.

BACKGROUND: Post-cardiac surgery surgical site infections (SSIs) pose devastating consequences in terms of morbidity and mortality to patients. OBJECTIVE: To examine current risk factors and best practice perioperative care for prevention of SSI following cardiac surgery through the lens of the demographic/clinical characteristics of patients who developed post-cardiac surgery SSIs at a major tertiary care institution, and to identify where documentation is lacking and could be improved to better serve clinical practice. METHODS: A literature review on post-cardiac surgery SSI prevention and risk factors was performed. These risk factors were examined through a retrospective chart review of the population of patients who developed SSIs during the study period. RESULTS: The study population was characterized by a high prevalence of riskfactors including age, diabetes, obesity, operative time, blood glucose control, surgical re-exploration, blood transfusions, and emergency context, as well as differences from best practice guidelines such as preoperative showering. Compared to other populations in the literature, several ofthese risk factors were more prevalent at the study site than in the other comparable populations. CONCLUSION: The patient population had a relatively high prevalence of riskfactors, and the care received by these patients varied in some ways from best practices. Using best practice guidelines, known risk factors, and the data specific to the institution can provide insightsfor analysis and practice improvement efforts in the form of identifying at-risk patients, improving adherence to best practice guidelines, targeting areas to focus care efforts, and improving clincal documentation.

A prospective cohort study of acute kidney injury in multi-stage ultramarathon runners: the Biochemistry in Endurance Runner Study (BIERS).

The purpose of the study was to evaluate the prevalence of acute kidney injury (AKI) during a multi-stage ultramarathon foot race. A prospective observational study was taken during the Gobi 2008; Sahara 2008; and Namibia 2009 RacingThePlanet 7-day, 6-stage, 150-mile foot ultramarathons. Blood was analyzed before, and immediately after stage 1 (25 miles), 3 (75 miles), and 5 (140 miles). Creatinine (Cr), glomerular filtration rate (GFR), and incidence of AKI were calculated and defined by RIFLE criteria. Thirty participants (76% male, mean age 40 + 11 years) were enrolled. There were significant declines in GFR after each stage compared with the pre-race baseline (p < 0.001), with the majority of participants (55-80%) incurring AKI. The majority of study participants encountered significant renal impairment; however, no apparent cumulative effect was observed, with resolution of renal function to near baseline levels between stages.

Sleep Deficiency in Young Children.

There is growing public health concern about the high prevalence of sleep deficiency in early childhood and the associated risk for sleep-associated poor health outcomes, including metabolic, cardiovascular, and mental health. The recent shift to conceptualize sleep health as a multidimensional construct, influenced by socioecological factors, highlights the potential role of sleep in health disparities. Understanding the development of sleep health and the emergence of sleep disorders in early life is a current priority in pediatric sleep research. Future behavioral sleep interventions should consider the multiple socioecological influences on children's sleep health and be tested using inclusive sampling methods.

A Cross-Sectional Evaluation of the Virtual Outpatient Management of People With Mpox.

Background: To report on the implementation and outcomes of a virtual ward established for the management of mpox during the 2022 outbreak, we conducted a 2-center, observational, cross-sectional study over a 3-month period. Methods: All patients aged ≥17 years with laboratory polymerase chain reaction-confirmed monkeypox virus managed between 14 May and 15 August 2022, at the Hospital for Tropical Diseases at University College London Hospitals National Health Service (NHS) Foundation Trust and sexual health services at Central North and West London NHS Foundation Trust, were included. Main outcomes included the proportion of patients managed exclusively on the virtual ward, proportion of patients requiring inpatient admission, proportion of patients with human immunodeficiency virus, and duration of lesion reepithelialization. Results: Among confirmed cases (N = 221), 86% (191/221) were managed exclusively on the virtual ward, while 14% (30/221) required admission. Treatment for concomitant sexually transmitted infections was provided to 25% (55/221) of patients, antibiotics for other infective complications to 16% (35/221), and symptomatic relief to 27% (60/221). The median time from onset to complete lesion reepithelialization and de-isolation was 18 days (range, 8-56 days). Eleven percent (24/221) of individuals disengaged from services within 4 days of testing. Conclusions: The virtual ward model facilitated safe and holistic outpatient management of mpox, while minimizing admissions. This approach could serve as a model for future outbreak responses.

Evaluation of a remote monitoring service for patients with COVID-19 discharged from University College London Hospital.

INTRODUCTION: In May 2020 a virtual ward for COVID-19 patients seen at University College London Hospital (UCLH) was established. The aim of this study was to see if specific factors can be used to predict the risk of deterioration and need for Emergency Department (ED) reattendance or admission. METHODS: We performed a service evaluation of the COVID-19 virtual ward service at UCLH between 24/10/2020 and 12/2/2021. 649 patients were included with data collected on vital signs, basic measurements, and blood tests from their initial ED attendance, allowing calculation of ISARIC-4C mortality scores. Outcomes of interest were ED reattendance, facilitation of this by virtual ward physician, level of care if admitted, and death within 28 days of the first COVID-19 virtual ward appointment. Analysis was performed using Mann-Whitney U tests. RESULTS: Reattendance rate to ED was 17.3% (112/649) of which 8% (51/649) were admitted. Half of ED reattendances were facilitated by the virtual ward service. Overall mortality was 0.92%. Patients who reattended ED, facilitated by the virtual ward service, had a higher mean CRP (53.63 vs 41.67 mg/L), presented to ED initially later in their COVID-19 illness (8 vs 6.5 days) and had a higher admission rate (61 vs 39%). The mean ISARIC-4C score was higher in the reattendance group compared to the non-reattendance group (3.87 vs 3.48, difference of 0.179, p = 0.003). The mean ISARIC-4C score was higher in the admission group than the non-reattendance group (5.56 vs 3.48, difference of 0.115, p = 0.003). CONCLUSION: Identification of patient risk factors for reattendance following a diagnosis of COVID-19 in ED can be used to design a service to safely manage patients remotely. We found that the ISARIC -4C mortality score was associated with risk of hospital admission and could be used to identify those requiring more active remote follow up.

Research activity among physicians in the United Kingdom: results from the Royal College of Physicians Census 2022.

We present the results of the 2022 Census of the Federation of Royal Colleges of Physicians of Edinburgh, Glasgow and London on whether physicians undertake research and the barriers they have encountered. 40% of physicians reported that they undertook research alongside their clinical work. Multivariate analysis of the responses showed that men were 1.6 times more likely to say they undertake research than women. The main barriers to undertaking research were having enough time, organisational factors and a lack of confidence. In this opinion piece we discuss some of the challenges and how they could be addressed.