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Abstract High‐dose melphalan followed by stem cell rescue is the standard consolidative therapy for transplant‐eligible patients with multiple myeloma (MM) in the United Kingdom. A melphalan dose of 200 mg/m2 (Mel200) is considered the “gold standard” for autologous stem cell transplant (ASCT) conditioning for fit patients ≤70 years old; however, with a peak diagnosis incidence at 80–89 years old in the UK dose adjustments will be inevitable to limit toxicities. In this single‐centre UK‐based retrospective analysis, data was collected from patients with plasma cell dyscrasias who underwent a first reduced‐intensity, Mel140, ASCT from 2006 to 2019, a total of 81 patients. We found that the procedure was overall safe with seven (9%) of patients requiring ITU admission and a single transplant‐related death within the initial autograft admission. The progression‐free survival (PFS) and overall survival were comparable with those previously reported in the literature with median PFS for our cohort of 31 months. Univariate analysis of our data showed an inferior PFS for patients aged ≥70 years. In conclusion, although this is a retrospective analysis, it demonstrates that dose‐reduced melphalan conditioning is safe and effective in patients deemed unfit for standard‐intensity conditioning.

Abstract Brexucabtagene autoleucel (brexu‐cel) is an autologous CD19 CAR T‐cell product, approved for relapsed/refractory (r/r) mantle cell lymphoma (MCL). In ZUMA‐2, brexu‐cel demonstrated impressive responses in patients failing ≥2 lines, including a bruton's tyrosine kinase inhibitor, with an overall and complete response rate of 93% and 67%, respectively. Here, we report our real‐world intention‐to‐treat (ITT) outcomes for brexu‐cel in consecutive, prospectively approved patients, from 12 institutions in the United Kingdom between February 2021 and June 2023, with a focus on feasibility, efficacy, and tolerability. Of 119 approved, 104 underwent leukapheresis and 83 received a brexu‐cel infusion. Progressive disease (PD) and/or manufacturing (MF) were the most common reasons for failure to reach harvest and/or infusion. For infused patients, best overall and complete response rates were 87% and 81%, respectively. At a median follow‐up of 13.3 months, median progression‐free survival (PFS) for infused patients was 21 months (10.1–NA) with a 6‐ and 12‐month PFS of 82% (95% confidence interval [CI], 71–89) and 62% (95% CI, 49–73), respectively. ≥Grade 3 cytokine release syndrome and neurotoxicity occurred in 12% and 22%, respectively. On multivariate analysis, inferior PFS was associated with male sex, bulky disease, ECOG PS > 1 and previous MF. Cumulative incidence of non‐relapse mortality (NRM) was 6%, 15%, and 25% at 6, 12, and 24 months, respectively, and mostly attributable to infection. Outcomes for infused patients in the UK are comparable to ZUMA‐2 and other real‐world reports. However, ITT analysis highlights a significant dropout due to PD and/or MF. NRM events warrant further attention.

Abstract Objective: To determine the safety of noncarbapenem versus carbapenem antibiotics for treatment of adults with documented infection caused by ceftriaxone-resistant infections outside the urinary tract. Design: Retrospective cohort of adult patients with a documented infection caused by an extended-spectrum β-lactamase (ESBL)–producing organism isolated between January 2018 and October 2021. Setting: An academic tertiary-care center. Patients: Adult patients with a documented infection caused by an ESBL-producing organism outside the urinary tract. Methods: The primary outcome was a composite of treatment failure defined as 30-day mortality, 30-day readmission, microbiological recurrence, and/or clinical worsening requiring antibiotic change. Secondary outcomes included differentiation of primary composite components and postantibiotic Clostridioides difficile infection (CDI). Results: This study included 130 patients. The primary source of infections were bloodstream (67.7%) and caused by Escherichia coli (81.5%). Overall, 101 patients received carbapenem therapy and 29 received noncarbapenem therapy (NCT). NCT was comprised of mainly fluoroquinolones (18 of 29) followed by cefepime (7 of 29). Patients receiving NCT had shorter hospital stays (median, 7 days vs 9 days) and were more often discharged on antibiotics (79.3% vs 50.5%). We did not detect a significant difference in the primary composite outcome of treatment failure for carbapenem (23.8%) versus noncarbapenem treatment (24.2%; P = .967). Secondary outcomes included a numerically higher 30-day mortality rate in the noncarbapenem group compared to the carbapenem group: 4 (13.8%) of 29 versus 4 (3.9%) of 101. We did not detect a difference in rates of CDI. Conclusion: Noncarbapenem therapy may play a role for certain patients with infections caused by ESBL-producing organisms.

Background: Paclitaxel is commonly used as first-line chemotherapy for HER2-negative metastatic breast cancer (MBC) patients. However, with response rates of 21.5–53.7% and significant risk of peripheral neuropathy, there is need for better chemotherapy. Patients and methods: This open-label phase II/III trial randomised HER2-negative MBC patients 1:1 to either 6 cycles of three-weekly cabazitaxel (25 mg/m2), or, weekly paclitaxel (80 mg/m2) over 18 weeks.The primary endpoint was progression free survival (PFS). Secondary endpoints included objective response rate (ORR), time to response (TTR), overall survival (OS), safety and tolerability and quality of life (QoL). Results: 158 patients were recruited. Comparing cabazitaxel to paclitaxel, median PFS was 6.7 vs 5.8 months (HR 0.87; 80%CI 0.70–1.08, P = 0.4). There was no difference in median OS (20.6 vs 18.2 months, HR 1.00; 95%CI 0.69–1.45, P = 0.99), ORR (41.8% vs 36.7%) or TTR (HR 1.09; 95%CI 0.68–1.75, P = 0.7).Grade ≥3 adverse events occurred in 41.8% on cabazitaxel and 46.8% on paclitaxel; the most common being neutropenia (16.5%) and febrile neutropenia (12.7%) cabazitaxel and neutropenia (8.9%) and lung infection (7.6%) paclitaxel. Peripheral neuropathy of any grade occurred in 54.5% paclitaxel vs 16.5% cabazitaxel.Mean EQ-5D-5L single index utility score (+0.05; 95%CI 0.004–0.09, P = 0.03) and visual analogue scale score (+7.7; 95%CI 3.1–12.3, P = 0.001) were higher in cabazitaxel vs paclitaxel. Conclusions: Three-weekly cabazitaxel in HER2-negative MBC does not significantly improve PFS compared to weekly paclitaxel, although it has a lower risk of peripheral neuropathy with better patient reported QoL outcomes. It is well tolerated and requires fewer hospital visits.

Aims With increasing burden of revision hip arthroplasty (THA), one of the major challenges is the management of proximal femoral bone loss associated with previous multiple surgeries. Proximal femoral arthroplasty (PFA) has already been popularized for tumour surgeries. Our aim was to describe the outcome of using PFA in these demanding non-neoplastic cases. Methods A retrospective review of 25 patients who underwent PFA for non-neoplastic indications between January 2009 and December 2015 was undertaken. Their clinical and radiological outcome, complication rates, and survival were recorded. All patients had the Stanmore Implant – Modular Endo-prosthetic Tumour System (METS). Results At mean follow-up of 5.9 years, there were no periprosthetic fractures. Clearance of infection was achieved in 63.6% of cases. One hip was re-revised to pseudo arthroplasty for deep infection. Instability was noted in eight of the hips (32%), of which seven needed further surgery. Out of these eight hips with instability, five had preoperative infection. Deep infection was noted in five of the hips (20%), of which four were primarily revised for infection. One patient had aseptic loosening of the femoral component and awaits revision surgery. The Kaplan-Meier survivorship free of revision of any component for any reason was 72% (95% confidence interval (CI) 51.3% to 92.7%), and for revisions of only femoral component for any reason was 96% (95% CI 86.3% to 105.7%) at five years. Conclusion Dislocation and infection remain the major cause for failure, particularly in patients with pre-existing infection. The use of dual mobility cups, silver-coated implants, and less aggressive postoperative rehabilitation regimens would possibly aid in the reduction of complications. PFA performed in patients with periprosthetic fracture seem to fair better. This study supports the judicious use of PFA in non-oncological revision hip arthroplasties, and that they be performed by experienced revision arthroplasty surgeons. Cite this article: Bone Jt Open 2022;3(3):229–235.

Introduction: Establishment of strong emergency medical services (EMS) systems plays a pivotal role in reducing morbidity and mortality, especially in low and middle-income countries. We aimed to study the EMS utilization and resources available in the ambulances to deliver prehospital care among patients presenting to the Emergency Medicine Department in a tertiary care hospital in south India. Methods: Data regarding prehospital transport practices such as mode of arrival, utilization of EMS, resources available in the ambulance, presenting complaints, triage category, and demographic details were collected and analyzed. Subgroup analysis for time-sensitive complaints was done. Variables were subjected to univariate and multivariate analysis to find the predictors of ambulance usage. Results: The study included 3935 patients. The most common time-sensitive complaints were trauma (17%) and chest pain (11.5%). The most preferred mode of transport was the personal vehicle (45.6%). 29.8% of patients arrived in the ambulance. 97.7% of ambulances were not Advanced Cardiac Life Support equipped and 87.1% did not have an accompanying health care provider. 64.5% inter-hospital patient transfers were through ambulance, 83.8% transfers were unaccompanied. Among patients with time-sensitive complaints, EMS utilization was inadequate (46.8% in acute coronary syndrome, 34% in trauma, and 56.5% in early acute ischemic stroke). Conclusion: There was underutilization of the EMS services. Majority of the ambulances were not adequately equipped/staffed to deliver prehospital interventions. Policies at national level are required to encourage EMS utilization by the public and urgent measures are needed to improve services provided by them.

Background: India does not have a formal cardiac arrest registry or a centralized emergency medical system. In this study, we aimed to assess the prehospital care received by the patients with OHCA and predict the factors that could influence their outcome. Methods: Out-of-hospital cardiac arrest patients presenting to the emergency department in a tertiary care centre were included in the study. Prehospital care was assessed in terms of bystander cardiopulmonary resuscitation (CPR), mode of transport, resuscitation in ambulance. OHCA outcomes like Return of spontaneous circulation (ROSC), survival to hospital discharge and favourable neurological outcome at discharge were assessed. Results: Among 205 patients, the majority were male (71.2%) and were above 60 years of age (49.3%); Predominantly non-traumatic (82.4%). 30.7% of the patients had sustained cardiac arrest in transit to the hospital. 41.5% of patients reached hospital by means other than ambulance. Only 9.8% patients had received bystander CPR. Only 12.5% ambulances had BLS trained personnel. AED was used only in 1% of patients. The initial rhythm at presentation to the hospital was non-shockable (96.5%). Return of spontaneous circulation (ROSC) was achieved in 17 (8.3%) patients, of which only 3 (1.4%) patients survived till discharge. The initial shockable rhythm was a significant predictor of ROSC (OR 18.97 95%CI 3.83–93.89; p

Background: In March–April 2021, 23 patients at a 906-bed hospital in Delaware had surgical implantation of a bone graft product contaminated with Mycobacterium tuberculosis; 17 patients were rehospitalized for surgical site infections and 6 developed pulmonary tuberculosis. In May 2021, we investigated this tuberculosis outbreak and conducted a large, multidisciplinary, contact investigation among healthcare personnel (HCP) and patients potentially exposed over an extended period in multiple departments. Methods: Exposed HCP were those identified by their managers as present, without the use of airborne precautions, in operating rooms (ORs) during index spine surgeries or subsequent procedures, the postanesthesia care unit (PACU) when patients had draining wounds, inpatient rooms when wound care was performed, and the sterile processing department (SPD) on the days repeated surgeries were performed. We created and assigned an online education module and symptom screening questionnaire to exposed HCP. Employee health services (EHS) instituted a dedicated phlebotomy station to provide interferon-γ release assay (IGRA) testing for HCP at ≥8 weeks after last known exposure. EHS managed all exposed HCP, including nonemployees (eg, private surgeons) via automated e-mail reminders, which were escalated through supervisory chains as needed until follow-up completion. The infection prevention team notified exposed patients, defined as those who shared semiprivate rooms with case patients with transmissible tuberculosis. The Delaware Division of Public Health performed IGRA testing. Results: There were 506 exposed HCP in ORs (n = 100), the PACU (n = 87), inpatient units (n = 140), the SPD (n = 54), and other locations (n = 122); 83% were employed by the health system. Surgical masks and eye protection were routinely used during patient care. All exposed HCP completed screening by December 17, 2021. Furthermore, 2 HCP had positive IGRAs without symptoms or chest radiograph abnormalities, indicating latent tuberculosis infection, but after further review of records and interviews, we discovered that they had previously tested positive and had been treated for latent tuberculosis infection. In addition, 5 exposed patients tested negative and 2 remain pending. Conclusions: This large investigation demonstrated the need for a systematic process that encompassed all exposed HCP including nonemployees and incorporated administrative controls to ensure complete follow-up. We did not identify any conversions related to this outbreak despite high burden of disease in case patients and multiple exposures to contaminated bone-graft material and infectious bodily fluids without respirator use. Transmission risk was likely reduced by baseline surgical mask use and rapid institution of airborne precautions after outbreak recognition.

Background: Nearly one-third of patients on hemodialysis receive intravenous (IV) antibiotics annually, but national data characterizing antibiotic use in this population are limited. Using NHSN surveillance data for outpatient dialysis facilities, we estimated temporal changes in the rate of IV antibiotic starts (IVAS) among hemodialysis patients as well as the proportion of IVAS that were not supported by a reported clinical indication. Methods: IVAS events were obtained from the NHSN Dialysis Event module between 2016 and 2020, excluding patients who were out of network, receiving peritoneal or home dialysis, or with unspecified vascular access. IVAS unsupported by documentation were defined as new IVAS without a collected or positive blood culture, pus, redness or swelling event, or an associated clinical symptom. Pooled mean rates of total and unsupported IVAS were estimated per 100 patient months yearly and stratified by vascular access type. Differences in IVAS rates by year were estimated with negative binomial regression. Results: Between 2016 and 2020, 7,278 facilities reported 648,410 IVAS events; 161,317 (25%) were unsupported by documentation (Table 1). In 2016, 3,340 (54%) facilities with ≥1 IVAS event reported an IVAS unsupported by documentation, which increased to 4,994 (73%) in 2020. Total IVAS rates decreased by an average of 8.2% annually (95% CI, 7.1%–9.3%; P < .001). The average annual percentage decrease did not differ significantly by vascular access site. The total IVAS rate was lowest in 2020 (2.17 per 100 patient months; 95% CI, 2.18–2.17). IVAS rates in 2020 were greatest for patients with catheter access (4.79 per 100 patient months; 95% CI, 4.75–4.83), followed by graft (1.71 per 100 patient months; 95% CI, 1.68–1.73), and lowest for patients with fistulas (1.30 per 100 patient months; 95% CI, 1.29–1.31). The overall pooled mean rate of unsupported IVAS was 0.64 per 100 patient months (95% CI, 0.63–0.64), which did not significantly change by year (Fig. 1). Conclusions: Total IVAS rates among outpatient hemodialysis patients have decreased since 2016, and rates among catheter patients remain highest compared to patients with fistulas or grafts. However, unsupported IVAS rates did not change, and the proportion of facilities reporting an unsupported IVAS increased annually. Targeted efforts to engage facilities with unsupported IVAS may help improve accurate reporting and prescribing practices.

Aim: Emergency intensive care of the elderly is often complicated and multifaceted. Understanding the clinical profile of elderly patients admitted in an emergency department-intensive care unit (ED-ICU) is crucial in planning health policies in geriatric emergency medicine. Thus, the aim of the study was to create a local registry of elderly people utilizing the ED-ICU services and to understand the rate and predictors of mortality. Methods: A retrospective chart analysis was performed including all patients aged ≥60 years who had an ED-ICU admission during a 6-month period (August 2018–January 2019). A structured case record form was used to capture information such as basic demography, clinical profile, and outcomes. Results: Total number of records considered for final analysis were 503. Mortality was seen in 21.07% (n = 106/503). The most common presenting complaint and cause of death was breathing difficulty (n = 48/503; 29.42%) and pneumonia (n = 41/106; 38.67%), repectively. The significant predictors of mortality [adjusted odds ratio; 95% confidence intervals; P value] were hypertension (2.195; 1.255, 3.840; 0.006), chronic liver disease (CLD) (4.324; 1.170, 15.979; 0.028), malignancy (2.854; 1.045, 7.796; 0.041), requiring noninvasive ventilation (NIV) (2.618; 1.449, 4.730; 0.001), requiring intubation (6.638; 3.705, 11.894;

Abstract Background Where each patient has all three conduits of internal mammary artery (IMA), saphenous vein graft (SVG) and radial artery (RA), most confounders affecting comparison between conduits can be mitigated. Additionally, since SVG progressively fails over time, restricting patient angiography to the late period only can mitigate against early SVG patency that may have occluded in the late period. Methods Research protocol driven conventional angiography was performed for patients with at least one of each conduit of IMA, RA and SVG and a minimum of 7 years postoperative. The primary analysis was perfect patency and secondary analysis was overall patency including angiographic evidence of conduit lumen irregularity from conduit atheroma. Multivariable generalized linear mixed model (GLMM) was used. Patency excluded occluded or “string sign” conduits. Perfect patency was present in patent grafts if there was no lumen irregularity. Results Fifty patients underwent coronary angiography at overall duration postoperative 13.1 ± 2.9, and age 74.3 ± 7.0 years. Of 196 anastomoses, IMA 62, RA 77 and SVG 57. Most IMA were to the left anterior descending territory and most RA and SVG were to the circumflex and right coronary territories. Perfect patency RA 92.2% was not different to IMA 96.8%, P = 0.309; and both were significantly better than SVG 17.5%, P

Background: Uncorrected maternal hypotension occurring during obstetric emergencies may result in maternal and fetal morbidity. Fluid status of the pregnant mother is a major variable which affects the maternal hemodynamics during patient management, and there is no objective assessment tool for the same. A relatively new sonographic parameter, the inferior vena cava aorta (IVC/Ao) diameter index or caval aortic index, showed promise in this regard, and its application was studied in obstetric patients. Methodology: A prospective analytical study was conducted involving 50 pregnant and 50 nonpregnant women of reproductive age group. Using both subxiphoid and transhepatic views, their normal fasting caval aortic indices were determined from the ratio of mean IVC diameter to the mean aortic diameter. Descriptive and inferential statistical analyses were carried out accordingly. Results: Normal IVC/Ao diameter index for nonpregnant healthy women of reproductive age was 1.11 ± 0.29 in the subxiphoid view and 1.21 ± 0.33 in the transhepatic view. The difference between the two views was not statistically significant. IVC/Ao diameter index for a normal term pregnant woman was 1.03 ± 0.26, and term pregnancy does not significantly cause variation in the index. Conclusions: Caval aortic index is a useful noninvasive tool to assess volume status and guide fluid management in pregnant women presenting to the emergency department, and the transhepatic view is comparable to the traditional subxiphoid view for the measurement of the same.

As the world battles COVID-19, talks are rife about vaccine distribution and health policy overhauls. Amongst all this mayhem a section of patients suffers silently. The patients with chronic systemic diseases requiring regular care at the hospital for follow-ups and dialysis are getting lost in the crowd of COVID suspects. This paper narrates the harrowing ordeal of a patient shunted across hospitals all because of a fever, and in the end it discloses her eventual diagnosis.

BackgroundThe treatment paradigm for multiple myeloma (MM) continues to evolve with the development of novel therapies and the earlier adoption of continuous treatments into the treatment pathway. Lenalidomide-refractory patients now represent a challenge with inferior progression free survival (PFS) reported to subsequent treatments. We therefore sought to describe the natural history of MM patients following lenalidomide in the real world.MethodsThis was a retrospective cohort review of patients with relapsed MM who received lenalidomide-based treatments in the U.K. Data were collected for demographics, subsequent therapies, treatment responses, survival outcomes and clinical trial enrollment.Results198 patients received lenalidomide-based treatments at a median of 2 prior lines of therapy at a median of 41 months (range 0.5-210) from diagnosis. 114 patients (72% of 158 evaluable) became refractory to lenalidomide. The overall survival (OS) after lenalidomide failure was 14.7 months having received between 0-6 subsequent lines of therapy. Few deep responses were observed with subsequent treatments and the PFS to each further line was < 7 months. There was a steep reduction in numbers of patients able to receive further treatment, with an associated increase in number of deaths. The OS of patients progressing on lenalidomide who did not enter a clinical trial incorporating novel agents was very poor (8.8 months versus 30 months, p 0.0002), although the trials group were a biologically fitter group.ConclusionThese data demonstrate the poor outcomes of patients failing lenalidomide-based treatments in the real world, the highlight need for more effective treatments.

The anterior cruciate ligament (ACL) is one of the main stabilizing structures of the knee and its rupture is a common injury in young active adults. ACL reconstruction has been the preferred operative management of an ACL rupture for several decades; however, success rates are variable. Recently, interest in arthroscopic primary repair of the ligament has increased. The repair is augmented with an Internal Brace (IB), which is an ultra-high strength suture tape that bridges the ligament. This technique protects the ligament during the healing and the ligament is encouraged to heal naturally, whilst not requiring any external braces. It acts as a stabiliser to permit early mobilization and optimise rehabilitation. As understanding of rehabilitation has progressed, there has been an increased focus on early weight-bearing and achieving full range of movement. While detailed criterion-based rehabilitation protocols exist for ACL reconstruction, this is not the case for ACL repair. The purpose of this commentary is to present a novel criterion-based rehabilitation protocol following ACL repair surgery augmented with an IB. # Level of Evidence V

This article reports the synthesis of PEGylated microspheres of MoS2 nanosheets through the hydrothermal method and its application in rhodamine B and methylene blue dyes photodegradation, and photoreduction of chromium(VI) to chromium(III) in water under illumination with visible light. The catalyst was characterized using X-ray Diffraction (XRD), Transmission Electron Microscopy (TEM), Field Emission Scanning Electron Microscopy (FESEM), Energy Dispersive X-ray Spectroscopy (EDS), Fourier Transform Infra Red (FTIR), Thermo-gravimetric Analysis (TGA), and UV-Vis spectroscopies. XRD result reveals the MoS2 nanosheets to be present in the hexagonal phase of MoS2. SEM, TEM, and HRTEM images show that the synthesised sample has spherical shapes made up of several thin sheets of MoS2. The catalyst showed visible light responsivity with a calculated band gap of 1.92 eV. The MoS2 nanosheets exhibited high degradation efficiency against both dyes. The RhB and MB dyes experienced degradation efficiencies of 97.30 % (RhB) and 98.05 % (MB) in 75 min 90 min, respectively. The MoS2 photocatalyst is also observed to be effective in photocatalytic reduction of Cr(VI) and displayed 91.05% reduction of Cr(VI) to Cr(III) in 75 min. The results reveal that the synthesised MoS2 nanosheet is a good photocatalytic material for degradation of dyes and reduction of Cr(VI) to Cr(III) in water.

The benefit of autologous stem cell transplantation (ASCT) in newly diagnosed myeloma patients, apart from supporting high dose chemotherapy, may include effects on T cell function in the bone marrow (BM). We report our exploratory findings on marrow infiltrating T cells early post-ASCT (day+100), examining phenotype and T cell receptor (TCR) repertoire, seeking correlations with timing of relapse. Compared to healthy donors (HD), we observed an increase in regulatory T cells (CD4+FoxP3+, Tregs) with reduction in CD4 T cells, leading to lower CD4:8 ratios. Compared to paired pre-treatment marrow, both CD4 and CD8 compartments showed a reduction in naïve, and increase in effector memory subsets, suggestive of a more differentiated phenotype. This was supported by increased levels of several immune-regulatory and activation proteins (ICOS, PD-1, LAG-3, CTLA-4 and GzmB) when compared with HD. Unsupervised analysis identified a patient subgroup with shorter PFS (p=0.031) whose BM contained increased Tregs, and higher immune-regulatory markers (ICOS, PD-1, LAG-3) on effector T cells. Using single feature analysis, higher frequencies of marrow PD-1+ on CD4+FoxP3- cells and Ki67+ on CD8 cells were independently associated with early relapse. Finally, studying paired pre-treatment and post-ASCT BM (n=5), we note reduced abundance of TCR sequences at day+100, with a greater proportion of expanded sequences indicating a more focused persistent TCR repertoire. Our findings indicate that, following induction chemotherapy and ASCT, marrow T cells demonstrate increased activation and differentiation, with TCR repertoire focusing. Pending confirmation in larger series, higher levels of immune-regulatory proteins on T cell effectors at day+100 may indicate early relapse.

Background: Patients with cancer are hypothesised to be at increased risk of contracting COVID-19, leading to changes in treatment pathways in those treated with systemic anti-cancer treatments (SACT). This study investigated the outcomes of patients receiving SACT to assess whether they were at greater risk of contracting COVID-19 or having more severe outcomes. Methods: Data was collected from all patients receiving SACT in two cancer centres as part of CAPITOL (COVID-19 Cancer PatIenT Outcomes in North London). The primary outcome was the effect of clinical characteristics on the incidence and severity of COVID-19 infection in patients on SACT. We used univariable and multivariable models to analyse outcomes, adjusting for age, gender and comorbidities. Results: A total of 2871 patients receiving SACT from 2 March to 31 May 2020 were analysed; 68 (2.4%) were diagnosed with COVID-19. Cancer patients receiving SACT were more likely to die if they contracted COVID-19 than those who did not [adjusted (adj.) odds ratio (OR) 9.84; 95% confidence interval (CI) 5.73–16.9]. Receiving chemotherapy increased the risk of developing COVID-19 (adj. OR 2.99; 95% CI = 1.72–5.21), with high dose chemotherapy significantly increasing risk (adj. OR 2.36, 95% CI 1.35–6.48), as did the presence of comorbidities (adj. OR 2.29; 95% CI 1.19–4.38), and having a respiratory or intrathoracic neoplasm (adj. OR 2.12; 95% CI 1.04–4.36). Receiving targeted treatment had a protective effect (adj. OR 0.53; 95% CI 0.30–0.95). Treatment intent (curative versus palliative), hormonal- or immunotherapy and solid versus haematological cancers had no significant effect on risk. Conclusion: Patients on SACT are more likely to die if they contract COVID-19. Those on chemotherapy, particularly high dose chemotherapy, are more likely to contract COVID-19, while targeted treatment appears to be protective.

Background: This study aims to compare the outcomes of COVID-19-positive disease in patients with a history of cancer to those without. Methods: We retrospectively collected clinical data and outcomes of COVID-19 positive cancer patients treated consecutively in five North London hospitals (cohort A). Outcomes recorded included time interval between most recent anti-cancer treatment and admission, severe outcome [a composite endpoint of intensive care unit (ITU) admission, ventilation and/or death] and mortality. Outcomes were compared with consecutively admitted COVID-19 positive patients, without a history of cancer (cohort B), treated at the primary centre during the same time period (1 March–30 April 2020). Patients were matched for age, gender and comorbidity. Results: The median age in both cohorts was 74 years, with 67% male, and comprised of 30 patients with cancer, and 90 without (1:3 ratio). For cohort B, 579 patients without a history of cancer and consecutively admitted were screened from the primary London hospital, 105 were COVID-19 positive and 90 were matched and included. Excluding cancer, both cohorts had a median of two comorbidities. The odds ratio (OR) for mortality, comparing patients with cancer to those without, was 1.05 [95% confidence interval (CI) 0.4–2.5], and severe outcome (OR 0.89, 95% CI 0.4–2.0) suggesting no increased risk of death or a severe outcome in patients with cancer. Cancer patients who received systemic treatment within 28 days had an OR for mortality of 4.05 (95% CI 0.68–23.95), p = 0.12. On presentation anaemia, hypokalaemia, hypoalbuminaemia and hypoproteinaemia were identified predominantly in cohort A. Median duration of admission was 8 days for cancer patients and 7 days for non-cancer. Conclusion: A diagnosis of cancer does not appear to increase the risk of death or a severe outcome in COVID-19 patients with cancer compared with those without cancer. If a second spike of virus strikes, rational decision making is required to ensure optimal cancer care.

The current global severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has magnified the risk to healthcare providers when inititiating airway management, and safe tracheal intubation has become of paramount importance. Mitigation of risk to frontline providers requires airway management to be an orchestrated exercise based on training and purposeful simulation. Role allocation and closed-loop communication form the foundation of this exercise. We describe a methodical, 10-step approach from decision-making and meticulous drug and equipment choices to donning of personal protective equipment, and procedural concerns. This bundled approach will help reduce unplanned actions, which in turn may reduce the risk of aerosol transmission during airway management in resource-limited settings.

Background: The coronavirus disease 2019 (COVID-19) pandemic has caused great financial and psychological havoc. Healthcare professionals (HCPs) are among the many groups of people who are in the frontline and facing a risk of direct exposure to the virus. This study aimed to assess the prevalence and predictors of stress, depressive, and anxiety symptoms among HCPs of India. Methods: It was a cross-sectional, online survey conducted in April 2020 among HCPs who are directly involved in the triage, screening, diagnosing, and treatment of COVID-19 patients and suspects. Stress was estimated using Cohen’s perceived stress scale. Depression and anxiety were assessed using the tools Public Health Questionnaire—9 and Generalized Anxiety Disorder—7. Predictors were analyzed using univariate and multivariate binary logistic regression. Results: A total of 433 online responses were obtained, and N = 350 were finally included. The prevalence (95% CI) of HCPs with high-level stress was 3.7% (2.2, 6.2), while the prevalence rates of HCPs with depressive symptoms requiring treatment and anxiety symptoms requiring further evaluation were 11.4% (8.3, 15.2) and 17.7% (13.9, 22.1), respectively. Women had approximately two times the increased odds of developing moderate- or high-level stress, depressive symptoms requiring treatment, and anxiety symptoms requiring further evaluation. Similarly, women staying in a hostel/temporary accommodation had two times the increased odds of developing depression or anxiety symptoms. Conclusion: The prevalence of stress, depressive, and anxiety symptoms among HCPs in India during the pandemic is comparable with other countries.

This study specifies a framework to evaluate an investment strategy combining a market assessment with a valuation method using a stochastic binomial real option model. The market assessment uses multi-criteria analysis to determine which markets should be targeted for commercialization of a genetically modified trait in a target crop. The stochastic binomial real option model is developed to determine whether commercialization is financially viable. The framework was applied to canola being developed using gene technology to increase its drought tolerance. Our results showed that drought-tolerant canola would be more profitable than conventional varieties, but it would only be sufficiently profitable to pursue commercialization in targeted regions or countries.

Background: Burnout is a syndrome explained as serious emotional depletion with poor adaptation at work due to prolonged occupational stress. It has three principal components namely emotional exhaustion(EE), depersonalization(DP) and diminished feelings of personal accomplishment(PA). Thus, we aimed at measuring the degree of burnout in doctors and nurses working in emergency medicine department (EMD) of 4 select tertiary care teaching hospitals in South India. Methods: A cross sectional survey was conducted among EMD professionals using a 30-item standardized pilot tested questionnaire as well as the Maslach burnout inventory. Univariate and Multivariate analyses were conducted using binary logistic regression models to identify predictors of burnout. Results: Total number of professionals interviewed were 105 of which 71.5% were women and 51.4% were doctors. Majority (78.1%) belonged to the age group 20-30 years. Prevalence of moderate to severe burnout in the 3 principal components EE, DP and PA were 64.8%, 71.4% and 73.3% respectively. After multivariate analysis, the risk factors [adjusted odds ratio (95% confidence intervals) for DP included facing more criticism [3.57(1.25,10.19)], disturbed sleep [6.44(1.45,28.49)] and being short tempered [3.14(1.09,9.09)]. While there were no statistically significant risk factors for EE, being affected by mortality [2.35(1.12,3.94)] and fear of medication errors [3.61(1.26, 10.37)] appeared to be significant predictors of PA. Conclusion: Degree of burn out among doctors and nurses is moderately high in all of the three principal components and some of the predictors identified were criticism, disturbed sleep, short tempered nature, fear of committing errors and witnessing death in EMD.

Pesticide poisoning is always a clinical conundrum for the emergency physician (EP), the complexity of which increases when the pesticide has no antidote! Over the past decade, there has been a sharp increase in cases of Amitraz poisoning, a pesticide routinely used in veterinary medicine, available without a prescription. The usual presentation includes bradycardia, hypotension, poor sensorium, and miosis. In the absence of accurate history, these clinical features can be confused with the cholinergic toxidrome of organophosphorus poisoning. There is a dearth of literature regarding the presentation and protocols for the management of Amitraz poisoning with data mostly based on animal studies and pediatric case reports. Currently, the available medical literature in the form of case reports and case series form an invaluable source of information to the EP to formulate a working diagnosis and methodical approach to this pesticide. Here, we present two case reports highlighting the characteristic clinical features and bringing to light how an organized approach to the toxin can give satisfactory results.

Homozygous and compound heterozygous pathogenic variants in GNB5 have been recently associated with a spectrum of clinical presentations varying from a severe multisystem form of the disorder including intellectual disability, early infantile developmental and epileptic encephalopathy, retinal abnormalities and cardiac arrhythmias (IDDCA) to a milder form with language delay, attention-deficit/hyperactivity disorder, cognitive impairment, with or without cardiac arrhythmia (LADCI). Approximately twenty patients have been described so far; here we report a novel case of a 2.5-year-old female who is a compound heterozygote for a frameshift and a missense variant in the GNB5 gene. Her clinical presentation is consistent with a moderate phenotype, corroborating the direct correlation between the type and pathogenic mechanism of the GNB5 genetic variant and the severity of related phenotype.

Smoking prevalence among individuals with mental and behavioral health needs is considerably higher compared to the general population, but evidence-based smoking cessation therapies are underutilized in mental and behavioral healthcare settings, despite the fact that these treatments are both safe and effective. The goal of this paper is to present the background, design and pilot of Project TEACH (Tobacco Education and Cessation in the Health System) developed to improve clinical practice by offering specialized training in the provision of smoking cessation interventions to care providers in community mental health centers in Texas. This is achieved through engaging the expertise of clinicians at the MD Anderson Cancer Center’s Tobacco Treatment Program and disseminating this expertise to care providers by means of a novel tele-mentoring approach called Project ECHO (Extension for Community Healthcare Outcomes). Evaluation of our pilot ECHO training project demonstrated that the training was very well received and resulted in self-reported enhancement of the providers’ professional practice. This is the first project to extend the collaborative ECHO model to train healthcare providers in smoking cessation. This approach has potential to reduce smoking rates among smokers with mental and behavioral health needs, and consequently contribute to the prevention of cancer and other chronic diseases in this vulnerable population.

Fusarium head blight (FHB or scab) economically devastates barley production. FHB is predominantly caused by Fusarium graminearum and has resulted in major reductions in the quality of barley in the United States. The most common source of economic loss is through development of potent mycotoxins in the grain, the most prominent of which, in the United States, is deoxynivalenol (DON). DON levels can be managed through a variety of techniques. This study presents the estimate of the statistical relationship among DON contamination in barley, FHB incidence and severity, and a variety of disease management techniques. Data from 22 field studies and a survey of barley producers are used to estimate the relationship. Fungicide applications reduce DON in barley in general and via complementary interactions with the barley cultivar. Genetic FHB resistance in barley varieties is an important determinant of DON levels, as well as previous crop and factors related to time and location. Taking care to avoid rotations with FHB host crops immediately prior to barley is also important to reduce DON levels in barley. These become key inputs into barley producer decisions for evaluating the economic value of adopting FHB management techniques.

Why does the capacity to think certain thoughts imply the capacity to think certain other, structurally related, thoughts? Despite decades of intensive debate, cognitive scientists have yet to reach a consensus on an explanation for this property of cognitive architecture---the basic processes and modes of composition that together afford cognitive capacity---called systematicity. Systematicity is generally considered to involve a capacity to represent/process common structural relations among the equivalently cognizable entities. However, the predominant theoretical approaches to the systematicity problem, i.e. classical (symbolic) and connectionist (subsymbolic), require arbitrary (ad hoc) assumptions to derive systematicity. That is, their core principles and assumptions do not provide the necessary and sufficient conditions from which systematicity follows, as required of a causal theory. Hence, these approaches fail to fully explain why systematicity is a (near) universal property of human cognition, albeit in restricted contexts. We review an alternative, category theory approach to the systematicity problem. As a mathematical theory of structure, category theory provides necessary and sufficient conditions for systematicity in the form of universal construction: each systematically related cognitive capacity is composed of a common component and a unique component. Moreover, every universal construction can be viewed as the optimal construction in the given context (category). From this view, universal constructions are derived from learning, as an optimization. The ultimate challenge, then, is to explain the determination of context. If context is a category, then a natural extension towards addressing this question is higher-order category theory, where categories themselves are the objects of construction.