Unveiling Disparities: Exploring Differential Attainment in Postgraduate Training Within Clinical Oncology.

AIMS: Differential attainment (DA) in post graduate medical training is a recognised challenge and refers to unexplained variation across groups when split by several protected characteristics. The Royal College of Radiology is committed to fostering diversity, inclusivity, and equality with the goal of narrowing existing gaps and improving training outcomes. MATERIALS AND METHODS: This was a mixed methods study aiming to understand the causes of DA with view to helping the RCR develop strategies to address this. A cross-sectional survey was completed by 140 clinical oncology trainees in September 2022. Trainees and trainers (17 and 6 respectively) from across England, Scotland, Wales and Northern Ireland, took part in focus group and interviews from August to December 2022. Quantitative and qualitative data merged and interpreted. RESULT: Results showed international medical graduates and trainees from ethnic minority backgrounds were more likely to encounter challenges. The qualitative findings were used to identify three themes through which these problems could be framed. The trainee as a "space invader," the hidden curriculum of clinical oncology training and the process of navigating and tacking the training journey. CONCLUSION: Differential attainment is the product of a complex interplay between the trainee, trainer, and the training environment. Therefore, interventions must be tailored to different people and contexts. At a national level, the RCR can adopt general policies to promote this such as mentorship programmes, protected time for supervision and cultural competency training. Efficacy of proposed interventions for trial and their impact on DA should be evaluated to drive evidence-based changes.

Guidance for assessment of the inflammation etiologic criterion for the GLIM diagnosis of malnutrition: A modified Delphi approach.

BACKGROUND & AIMS: The Global Leadership Initiative on Malnutrition (GLIM) approach to malnutrition diagnosis is based on assessment of three phenotypic (weight loss, low body mass index, and reduced skeletal muscle mass) and two etiologic (reduced food intake/assimilation and disease burden/inflammation) criteria, with diagnosis confirmed by fulfillment of any combination of at least one phenotypic and at least one etiologic criterion. The original GLIM description provided limited guidance regarding assessment of inflammation and this has been a factor impeding further implementation of the GLIM criteria. We now seek to provide practical guidance for assessment of inflammation in support of the etiologic criterion for inflammation. METHODS: A GLIM-constituted working group with 36 participants developed consensus-based guidance through a modified-Delphi review. A multi-round review and revision process served to develop seven guidance statements. RESULTS: The final round of review was highly favorable with 99 % overall "agree" or "strongly agree" responses. The presence of acute or chronic disease, infection or injury that is usually associated with inflammatory activity may be used to fulfill the GLIM disease burden/inflammation criterion, without the need for laboratory confirmation. However, we recommend that recognition of underlying medical conditions commonly associated with inflammation be supported by C-reactive protein (CRP) measurements when the contribution of inflammatory components is uncertain. Interpretation of CRP requires that consideration be given to the method, reference values, and units (mg/dL or mg/L) for the clinical laboratory that is being used. CONCLUSION: Confirmation of inflammation should be guided by clinical judgement based upon underlying diagnosis or condition, clinical signs, or CRP.

Guidance for assessment of the inflammation etiologic criterion for the GLIM diagnosis of malnutrition: A modified Delphi approach.

BACKGROUND: The Global Leadership Initiative on Malnutrition (GLIM) approach to malnutrition diagnosis is based on assessment of three phenotypic (weight loss, low body mass index, and reduced skeletal muscle mass) and two etiologic (reduced food intake/assimilation and disease burden/inflammation) criteria, with diagnosis confirmed by fulfillment of any combination of at least one phenotypic and at least one etiologic criterion. The original GLIM description provided limited guidance regarding assessment of inflammation, and this has been a factor impeding further implementation of the GLIM criteria. We now seek to provide practical guidance for assessment of inflammation. METHODS: A GLIM-constituted working group with 36 participants developed consensus-based guidance through a modified Delphi review. A multiround review and revision process served to develop seven guidance statements. RESULTS: The final round of review was highly favorable, with 99% overall "agree" or "strongly agree" responses. The presence of acute or chronic disease, infection, or injury that is usually associated with inflammatory activity may be used to fulfill the GLIM disease burden/inflammation criterion, without the need for laboratory confirmation. However, we recommend that recognition of underlying medical conditions commonly associated with inflammation be supported by C-reactive protein (CRP) measurements when the contribution of inflammatory components is uncertain. Interpretation of CRP requires that consideration be given to the method, reference values, and units (milligrams per deciliter or milligram per liter) for the clinical laboratory that is being used. CONCLUSION: Confirmation of inflammation should be guided by clinical judgment based on underlying diagnosis or condition, clinical signs, or CRP.

An Objective Analysis of Quality and Readability of Online Information for Patients seeking Cosmetic Surgery Abroad.

Increasing numbers of patients are travelling abroad to undergo cosmetic surgery. This is associated with complications that often become the responsibility of clinicians in the patients' home countries. While seemingly lower cost treatments abroad may seem attractive, prospective patients should be made aware of the hidden costs of postoperative complications and their associated morbidity. Many internet sources of information regarding these procedures originate from commercial providers in the form of advertisements, which may not highlight the potential complications to prospective patients. Our study aims to perform an objective analysis of the quality and readability of online information for patients seeking cosmetic surgery abroad using tools such as JAMA and DISCERN scores. We found that the majority of online information available to prospective and current patients regarding travelling abroad for cosmetic surgery is unregulated, distributed by commercial providers and often lacking relevant and reliable information. Due to the strong influence that the internet can have on patients' decision making, it is important that reputable, informative online material is circulated regarding these procedures. Further work needs to be done by professional bodies and medical professionals in the plastic surgery community to improve patient education in this area.

Lhermitte-Duclos disease (dysplastic cerebellar gangliocytoma) in the setting of cowden syndrome: a case report and literature review on COLD syndrome.

Lhermitte-Duclos Disease is a rare clinical entity involving a dysplastic lesion of the cerebellum. The dysplastic cerebellar ganglioblastoma is often seen in association with Cowden Syndrome, an autosomal dominant disorder consisting of a mutation in the phosphatase and homologous tensin (PTEN) gene. Characteristic findings on neuroimaging allow for a pre-operative diagnosis to be made, which guides further management of the condition. This report describes the diagnosis and management of Lhermitte-Duclos Disease in a 51-year-old lady, spanning a period of almost seven years. The characteristic radiological and histological findings are presented, along with the clinical features associated with Cowden Syndrome. This patient ultimately underwent surgical intervention for symptomatic relief, which is described here.

Novel experimental setup for megahertz X-ray diffraction in a diamond anvil cell at the High Energy Density (HED) instrument of the European X-ray Free-Electron Laser (EuXFEL).

The high-precision X-ray diffraction setup for work with diamond anvil cells (DACs) in interaction chamber 2 (IC2) of the High Energy Density instrument of the European X-ray Free-Electron Laser is described. This includes beamline optics, sample positioning and detector systems located in the multipurpose vacuum chamber. Concepts for pump-probe X-ray diffraction experiments in the DAC are described and their implementation demonstrated during the First User Community Assisted Commissioning experiment. X-ray heating and diffraction of Bi under pressure, obtained using 20 fs X-ray pulses at 17.8 keV and 2.2 MHz repetition, is illustrated through splitting of diffraction peaks, and interpreted employing finite element modeling of the sample chamber in the DAC.

The prevalence of potential drug-drug interactions in adults with intellectual disability.

BACKGROUND: There is a high use of medications in adults with intellectual disability (ID). One implication of taking multiple medications is the potential for drug-drug interactions (DDIs). However, despite this being well highlighted in the mainstream literature, little is known about the incidence or associations of DDIs in the ID population. METHODS: This study describes the prevalence, patterns and associations of potential DDIs in a total administrative sample of adults with ID known to services in Jersey. Demographic, health-related and medication data were collected from 217 adults known to ID services. Data were collected using a face-to-face survey. The Anatomical Therapeutic Chemical classification system was used to categorise medications, and Stockley's Drug Interaction Checker was used to classify potential DDIs. Drug-drug pairings were considered to be of clinical significance if they were to be 'avoided, adjusted, monitored or required further information'. RESULTS: Potential DDIs of clinical significance were common. Exposure to potential DDIs of clinical significance was associated with being female, taking more than five medications (polypharmacy), living in residential care and having more health conditions. A simple regression was used to understand the effect of number of prescribed medications on potential DDIs of clinical significance. Every prescribed drug led to a 0.87 (95% confidence interval: 0.72-1.00) increase in having a potential DDI of clinical significance. CONCLUSION: Adults with ID who live in residential care, who are female, exposed to polypharmacy and have more health conditions may be more likely to have potential DDIs of clinical significance. Urgent consideration needs to be given to the potential of DDIs in this population given their exposure to high levels of medication.

Hypomagnesemia at the time of autologous stem cell transplantation for patients with diffuse large B-cell lymphoma is associated with an increased risk of failure.

Magnesium is an essential element that is involved in critical metabolic pathways. A diet deficient in magnesium is associated with an increased risk of developing cancer. Few studies have reported whether a serum magnesium level below the reference range (RR) is associated with prognosis in patients with diffuse large B cell lymphoma (DLBCL). Using a retrospective approach in DLBCL patients undergoing autologous stem cell transplant (AHSCT), we evaluated the association of hypomagnesemia with survival. Totally, 581 patients eligible for AHSCT with a serum magnesium level during the immediate pre-transplant period were identified and 14.1% (82/581) had hypomagnesemia. Hypomagnesemia was associated with an inferior event-free (EFS) and overall survival (OS) compared to patients with a serum magnesium level within RR; median EFS: 3.9 years (95% CI: 1.63-8.98 years) versus 6.29 years (95% CI: 4.73-8.95 years) with HR 1.63 (95% CI: 1.09-2.43, p = 0.017) for EFS, and median OS: 7.3 years (95% CI: 2.91-upper limit not estimable) versus 9.7 years (95% CI: 6.92-12.3 years) with HR 1.90 (95% CI: 1.22-2.96, p = 0.005) for OS months 0-12, respectively. These findings suggest a potentially actionable prognostic factor for patients with DLBCL undergoing AHSCT.

Probing extreme states of matter using ultra-intense x-ray radiation.

Extreme states of matter, that is, matter at extremes of density (pressure) and temperature, can be created in the laboratory either statically or dynamically. In the former, the pressure-temperature state can be maintained for relatively long periods of time, but the sample volume is necessarily extremely small. When the extreme states are generated dynamically, the sample volumes can be larger, but the pressure-temperature conditions are maintained for only short periods of time (ps toµs). In either case, structural information can be obtained from the extreme states by the use of x-ray scattering techniques, but the x-ray beam must be extremely intense in order to obtain sufficient signal from the extremely-small or short-lived sample. In this article I describe the use of x-ray diffraction at synchrotrons and XFELs to investigate how crystal structures evolve as a function of density and temperature. After a brief historical introduction, I describe the developments made at the Synchrotron Radiation Source in the 1990s which enabled the almost routine determination of crystal structure at high pressures, while also revealing that the structural behaviour of materials was much more complex than previously believed. I will then describe how these techniques are used at the current generation of synchrotron and XFEL sources, and then discuss how they might develop further in the future at the next generation of x-ray lightsources.

The phase diagram of Ti-6Al-4V at high-pressures and high-temperatures.

We report results from a series of diamond-anvil-cell synchrotron x-ray diffraction and large-volume-press experiments, and calculations, to investigate the phase diagram of commercial polycrystalline high-strength Ti-6Al-4V alloy in pressure-temperature space. Up to ∼30 GPa and 886 K, Ti-6Al-4V is found to be stable in the hexagonal-close-packed, orαphase. The effect of temperature on the volume expansion and compressibility ofα-Ti-6Al-4V is modest. The martensiticα→ω(hexagonal) transition occurs at ∼30 GPa, with both phases coexisting until at ∼38-40 GPa the transition to theωphase is completed. Between 300 K and 844 K theα→ωtransition appears to be independent of temperature.ω-Ti-6Al-4V is stable to ∼91 GPa and 844 K, the highest combined pressure and temperature reached in these experiments. Pressure-volume-temperature equations-of-state for theαandωphases of Ti-6Al-4V are generated and found to be similar to pure Ti. A pronounced hysteresis is observed in theω-Ti-6Al-4V on decompression, with the hexagonal structure reverting back to theαphase at pressures below ∼9 GPa at room temperature, and at a higher pressure at elevated temperatures. Based on our data, we estimate the Ti-6Al-4Vα-ß-ωtriple point to occur at ∼900 K and 30 GPa, in good agreement with our calculations.

Clinical application of fish-oil intravenous lipid emulsion in adult home parenteral nutrition patients.

BACKGROUND: High-ω-6 polyunsaturated fatty acids (PUFAs) are noted to contribute to development of intestinal failure-associated liver disease (IFALD) in home parenteral nutrition (HPN). Fish oil (FO) has been added to latest generation of lipid injectable emulsion (ILE) to increase ω-3:ω-6 PUFA ratio; however, appropriate dose of FO to treat IFALD is unknown. METHODS: After approval of exclusive FO ILE in the US for pediatric patients, we noted 2 adult patients with ongoing IFALD despite transition to mixed-oil (MO) ILE. They were transitioned to off-label FO ILE after review of literature regarding use of FO ILE in adult HPN patients was conducted to guide management. RESULTS: The first case involves a 40-year-old female receiving HPN with IFALD refractory to MO ILE. MO ILE (with 15% FO) was provided at 50 g/d for 3 d/wk and combined with FO ILE at 50 g/d for 4 d/wk. This combination resulted in improvement in liver studies and allowed for decrease in dextrose calories. The second case involves a 49-year-old male receiving HPN (secondary to complications of necrotizing pancreatitis) who developed IFALD. FO ILE was used as the sole source of lipids and led to improvement in liver function tests. No evidence of essential fatty acid deficiency was found in either case. CONCLUSIONS: Current case presentations and review of literature support the use of FO ILE to increase ω-3 PUFAs in patients with IFALD refractory to MO ILE. Additional research is necessary to delineate the dose of FO ILE necessary to achieve benefit.

Role of vacuum assisted excision in minimising overtreatment of ductal atypias.

PURPOSE: B3 lesions are indeterminate lesions of uncertain malignant potential. They include lesions with and without epithelial atypia. Those with atypia include atypical intraductal epithelial proliferation (AIDEP)/atypical ductal hyperplasia (ADH) and flat epithelial atypia (FEA). They are traditionally managed with surgery. Vacuum assisted excision (VAE) allows larger samples to be obtained using a vacuum assisted biopsy (VAB) device, which equates to a surgical biopsy. We propose that VAE and mammographic surveillance is a safe alternative to surgery in managing the ductal atypias; (AIDEP/ADH and FEA). METHOD: Retrospective analysis of prospectively collected data on B3 lesions (April 2009 - March 2016) from consecutive breast screening patients diagnosed with AIDEP/ADH or FEA on initial diagnostic core biopsy. Mammographic abnormality, breast density, size, management pathway and upgrade to cancer and types of cancer were also collected during the treatment pathway and 5 year surveillance period (April 2009 - April 2019). RESULTS: 273 cases of ductal atypia were identified. 187/273 (68.5 %) cases were managed with VAE only as no upgrade to malignancy and then 5 year mammographic surveillance. 34/273 (12.5 %) cases had a VAE diagnosing malignancy. 24/273 (8.8 %) cases had a VAE and then a surgical biopsy due to radiological or pathological concern, 8/24 upgraded to malignancy. 22/273 (8%) cases had a surgical diagnostic biopsy, 9/22 (41 %) cases were upgraded to malignancy. In total 51/273 (19 %) cases were diagnosed with cancer on the new pathway (13 invasive (all ER positive and Her2 negative) and 38 non-invasive, (34 ductal carcinoma in situ (DCIS) and 4 cases of lobular carcinoma in situ (LCIS)). While 17/273 (6.2 %) cases developed malignancy (12 invasive (all HER2 negative) and 4 DCIS and 1 LCIS) during the 5 year surveillance period. CONCLUSIONS: VAE is a safe alternative to surgery in managing ductal atypias. 187/273 (68.5 %) women avoided surgery. While 34/51 cancers (66.7 %) were diagnosed preoperatively using VAE, allowing the women to have a single therapeutic procedure.

Polypharmacy and psychotropic polypharmacy in adults with intellectual disability: a cross-sectional total population study.

BACKGROUND: Adults with intellectual disability (ID) are prescribed high levels of medication, with polypharmacy and psychotropic polypharmacy common. However, reported rates vary between studies, and there has been an over-reliance on obtaining data from convenience samples. The objective of this study was to determine the prevalence of medication use and polypharmacy in a population-level sample of adults with IDs. Factors associated with polypharmacy and psychotropic polypharmacy are explored. METHODS: We used a total population sample of 217 adults with IDs known to services in Jersey (sampling frame n = 285). The Anatomical Therapeutic Chemical classification system was used to categorise medications that participants were currently taking on a regular basis. We examined associations of polypharmacy and psychotropic polypharmacy with socio-economic status, health and demographic variables using univariate and multivariate analyses. RESULTS: A total of 83.4% of participants were prescribed medication, with high doses common. Of the participants, 38.2% were exposed to polypharmacy while 23% of participants were exposed to psychotropic polypharmacy. After controlling for demographic, health and socio-economic characteristics, polypharmacy was significantly associated with older age, increased severity of ID, living in a residential setting and having increased comorbidities. Psychotropic polypharmacy was associated with being male, being aged 50+ years and having had a psychiatric diagnosis over the life course. Being prescribed psychotropic drugs above the defined daily dose was not associated with having had a psychiatric diagnosis over the life course, suggesting the possibility of 'off label' prescribing. CONCLUSIONS: Our results indicate that medication use, in high doses, alongside polypharmacy and psychotropic polypharmacy are highly prevalent in adults with ID. The exposure to multiple medications increases the risk of developing adverse drug events, drug-drug interactions and medication-related problems. Future population-level, prospective cohort studies should examine the prevalence of polypharmacy and psychotropic polypharmacy using standardised definitions and consider the potential impact of adverse drug events, drug-drug interactions and medication-related problems in this population.

Magnesium: The overlooked electrolyte in blood cancers?

Magnesium is an important element that has essential roles in the regulation of cell growth, division, and differentiation. Mounting evidence in the literature suggests an association between hypomagnesemia and all-cause mortality. In addition, epidemiologic studies have demonstrated that a diet poor in magnesium increases the risk of developing cancer, highlighting its importance in the field of hematology and oncology. In solid malignancies, hypomagnesemia at diagnosis portends a worse prognosis. However, little is known about prognosis in patients with hypomagnesemia and blood cancers in general; lymphoma more specifically. Hypomagnesemia has been associated with a higher viral load of the Epstein Barr virus, a virus associated with a multitude of hematologic malignancies. The role of magnesium in the immune system has been further elucidated in studies of patients with a rare primary immunodeficiency known as XMEN disease (X-linked immunodeficiency with Magnesium defect, Epstein-Barr virus (EBV) infection, and Neoplasia disease). These patients have a mutation in the MAGT1 gene, which codes for a magnesium transporter. The mutation leads to impaired T cell activation and an increased risk of developing hematologic malignancies. In this review we discuss the relevance of magnesium as an electrolyte, current measurement techniques, and the known data related to cause and prognosis of blood cancers. The goal is to use these data to stimulate additional high-quality and well powered studies to further investigate the role of magnesium in preventing cancer and improving outcomes of patients with malignancy and concomitant magnesium deficiency.

The high-pressure, high-temperature phase diagram of cerium.

We present an experimental study of the high-pressure, high-temperature behaviour of cerium up to ∼22 GPa and 820 K using angle-dispersive x-ray diffraction and external resistive heating. Studies above 820 K were prevented by chemical reactions between the samples and the diamond anvils of the pressure cells. We unambiguously measure the stability region of the orthorhombic oC4 phase and find it reaches its apex at 7.1 GPa and 650 K. We locate the α-cF4-oC4-tI2 triple point at 6.1 GPa and 640 K, 1 GPa below the location of the apex of the oC4 phase, and 1-2 GPa lower than previously reported. We find the α-cF4 → tI2 phase boundary to have a positive gradient of 280 K (GPa)-1, less steep than the 670 K (GPa)-1 reported previously, and find the oC4 → tI2 phase boundary to lie at higher temperatures than previously found. We also find variations as large as 2-3 GPa in the transition pressures at which the oC4 → tI2 transition takes place at a given temperature, the reasons for which remain unclear. Finally, we find no evidence that the α-cF4 → tI2 is not second order at all temperatures up to 820 K.

Containing a measles outbreak in Minnesota, 2017: methods and challenges.

AIMS: We report on a measles outbreak largely occurring in Minnesota's under-vaccinated Somali community in the spring of 2017. The outbreak was already into its third generation when the first two cases were confirmed, and rapid public health actions were needed. The aim of our response was to quickly end transmission and contain the outbreak. METHODS: The state public health department performed laboratory testing on suspect cases and activated an Incident Command staffed by subject matter experts that was operational within 2 h of case confirmation. Epidemiologic interviews identified exposures in settings where risk of transmission was high, that is, healthcare, childcare, and school settings. Vaccination status of exposed persons was assessed, and postexposure prophylaxis (PEP) was offered, if applicable. Exposed persons who did not receive PEP were excluded from childcare centers or schools for 21 days. An accelerated statewide measles, mumps, and rubella (MMR) recommendation was made for Somali Minnesota children and children in affected outbreak counties. Partnerships with the Somali Minnesota community were deepened, building off outreach work done with the community since 2008. RESULTS: Public health identified 75 measles cases from 30 March to 25 August 2017: 43% were female, 81% Somali Minnesotan, 91% unvaccinated, and 28% hospitalized. The median age of cases was 2 years (range: 3 months-57 years). Most transmission (78%) occurred in childcare centers and households. A secondary attack rate of 91% was calculated for unvaccinated household contacts. Over 51,000 doses of MMR were administered during the outbreak above expected baseline. At least 8490 individuals were exposed to measles; 155 individuals received PEP; and over 500 persons were excluded from childcare and school. State and key public health partners spent an estimated $2.3 million on response. CONCLUSION: This outbreak demonstrates the necessity of immediate, targeted disease control actions and strong public health, healthcare, and community partnerships to end a measles outbreak.

Parenteral Nutrition Drug Shortages: A Single-Center Experience With Rapid Process Change.

Disruptions in the medication supply chain and consequent drug product shortages, including shortages of parenteral products used for parenteral nutrition (PN) compounding, have become an increasingly common occurrence. The amino acid solution shortage that resulted from the devastating impact of Hurricanes Maria and Irma on manufacturing facilities in Puerto Rico in 2017 necessitated a rapid, coordinated shift from use of compounded PN to commercial multichamber-bag PN (MCB-PN) at our hospitals. We describe our experience operationalizing this intervention via a framework that may be adapted for addressing other drug product shortages to promote rapid yet safe use of therapeutic alternatives.