Attitudes of medical students to medical leadership and management: a systematic review to inform curriculum development.

BACKGROUND: There is a growing acknowledgement that doctors need to develop leadership and management competences to become more actively involved in the planning, delivery and transformation of patient services. We undertook a systematic review of what is known concerning the knowledge, skills and attitudes of medical students regarding leadership and management. Here we report the results pertaining to the attitudes of students to provide evidence to inform curriculum development in this developing field of medical education. METHODS: We searched major electronic databases and citation indexes within the disciplines of medicine, education, social science and management. We undertook hand searching of major journals, and reference and citation tracking. We accessed websites of UK medical institutions and contacted individuals working within the field. RESULTS: 26 studies were included. Most were conducted in the USA, using mainly quantitative methods. We used inductive analysis of the topics addressed by each study to identity five main content areas: Quality Improvement; Managed Care, Use of Resources and Costs; General Leadership and Management; Role of the Doctor, and Patient Safety. Students have positive attitudes to clinical practice guidelines, quality improvement techniques and multidisciplinary teamwork, but mixed attitudes to managed care, cost containment and medical error. Education interventions had variable effects on students' attitudes. Medical students perceive a need for leadership and management education but identified lack of curriculum time and disinterest in some activities as potential barriers to implementation. CONCLUSIONS: The findings from our review may reflect the relatively little emphasis given to leadership and management in medical curricula. However, students recognise a need to develop leadership and management competences. Although further work needs to be undertaken, using rigorous methods, to identify the most effective and cost-effective curriculum innovations, this review offers the only currently available summary of work examining the attitudes of students to this important area of development for future doctors.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Empagliflozin in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Background Empagliflozin has been proposed as a treatment for COVID-19 on the basis of its anti-inflammatory, metabolic, and haemodynamic effects. The RECOVERY trial aimed to assess its safety and efficacy in patients admitted to hospital with COVID-19. Methods In the randomised, controlled, open-label RECOVERY trial, several possible treatments are compared with usual care in patients hospitalised with COVID-19. In this analysis, we assess eligible and consenting adults who were randomly allocated in a 1:1 ratio to either usual standard of care alone or usual standard of care plus oral empagliflozin 10 mg once daily for 28 days or until discharge (whichever came first) using web-based simple (unstratified) randomisation with allocation concealment. The primary outcome was 28-day mortality; secondary outcomes were duration of hospitalisation and (among participants not on invasive mechanical ventilation at baseline) the composite of invasive mechanical ventilation or death. On March 3, 2023 the independent data monitoring committee recommended that the investigators review the data and recruitment was consequently stopped on March 7, 2023. The ongoing RECOVERY trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936). Findings Between July 28, 2021 and March 6, 2023, 4271 patients were randomly allocated to receive either empagliflozin (2113 patients) or usual care alone (2158 patients). Primary and secondary outcome data were known for greater than 99% of randomly assigned patients. Overall, 289 (14%) of 2113 patients allocated to empagliflozin and 307 (14%) of 2158 patients allocated to usual care died within 28 days (rate ratio 0·96 [95% CI 0·82–1·13]; p=0·64). There was no evidence of significant differences in duration of hospitalisation (median 8 days for both groups) or the proportion of patients discharged from hospital alive within 28 days (1678 [79%] in the empagliflozin group vs 1677 [78%] in the usual care group; rate ratio 1·03 [95% CI 0·96–1·10]; p=0·44). Among those not on invasive mechanical ventilation at baseline, there was no evidence of a significant difference in the proportion meeting the composite endpoint of invasive mechanical ventilation or death (338 [16%] of 2084 vs 371 [17%] of 2143; risk ratio 0·95 [95% CI 0·84–1·08]; p=0·44). Two serious adverse events believed to be related to empagliflozin were reported: both were ketosis without acidosis. Interpretation In adults hospitalised with COVID-19, empagliflozin was not associated with reductions in 28-day mortality, duration of hospital stay, or risk of progressing to invasive mechanical ventilation or death so is not indicated for the treatment of such patients unless there is an established indication due to a different condition such as diabetes. Funding UK Research and Innovation (Medical Research Council) and National Institute of Health Research (MC_PC_19056), and Wellcome Trust (222406/Z/20/Z)

Health effects of routine measles vaccination and supplementary immunisation activities in 14 high-burden countries: a Dynamic Measles Immunization Calculation Engine (DynaMICE) modelling study

Background: WHO recommends at least 95% population coverage with two doses of measles-containing vaccine (MCV). Most countries worldwide use routine services to offer a first dose of measles-containing vaccine (MCV1) and later, a second dose of measles-containing vaccine (MCV2). Many countries worldwide conduct supplementary immunisation activities (SIAs), offering vaccination to all people in a specific age range irrespective of previous vaccination history. We aimed to estimate the relative effects of each dose and delivery route in 14 countries with high measles burden. Methods: We used an age-structured compartmental dynamic model, the Dynamic Measles Immunization Calculation Engine (DynaMICE), to assess the effects of different vaccination strategies on measles susceptibility and burden during 2000–20 in 14 countries with high measles incidence (containing 53% of the global birth cohort and 78% of the global measles burden). Country-specific routine MCV1 and MCV2 coverage data during 1980–2020 were obtained from the WHO and UNICEF Estimates of National Immunization Coverage database for all modelled countries and SIA data were obtained from the WHO summary of measles and rubella SIAs. We estimated the incremental health effects of different vaccination strategies using prevented cases of measles and deaths from measles and their efficiency using the incremental number needed to vaccinate (NNV) to prevent an additional measles case. Findings: Compared with no vaccination, MCV1 implementation was estimated to have prevented 824 million cases of measles and 9·6 million deaths from measles, with a median NNV of 1·41 (IQR 1·35–1·44). Adding routine MCV2 to MCV1 was estimated to have prevented 108 million cases and 404 270 deaths, whereas adding SIAs to MCV1 was estimated to have prevented 256 million cases and 4·4 million deaths. Despite larger incremental effects, adding SIAs to MCV1 (median incremental NNV 6·02, 5·30–7·68) showed reduced efficiency compared with adding routine MCV2 (5·41, 4·76–6·11). Interpretation: Vaccination strategies, including non-selective SIAs, reach a greater proportion of children who are unvaccinated and reduce measles burden more than MCV2 alone, but efficiency is lower because of the wide age range targeted by SIAs. This analysis provides information to help improve the health effects and efficiency of measles vaccination strategies. The interplay between MCV1, MCV2, and SIAs should be considered when planning future measles vaccination strategies. Funding: Gavi, the Vaccine Alliance and the Bill & Melinda Gates Foundation

Sweet's syndrome in a patient with Crohn's disease: a case report

<p>Abstract</p> <p>Background</p> <p>Sweet's syndrome, also known as acute febrile neutrophilic dermatosis, has been associated with malignancy, autoimmune disease and collagen vascular disease. The association of Crohn's disease and Sweet's syndrome is rare. We report a case of Sweet's syndrome in a patient with Crohn's disease.</p> <p>Case presentation</p> <p>A 63-year-old man with a history of Crohn's disease presented with one-week duration of abdominal pain, diarrhea and hematochezia. He also noticed eruption of painful skin rashes all over his body at the same time. Colonoscopy and esophagogastroduodenoscopy (EGD) showed inflammation involving different parts of the gastrointestinal tract consistent with Crohn's disease. Punch biopsy of the skin lesion was consistent with Sweet's syndrome, which has a rare association with Crohn's disease.</p> <p>Conclusion</p> <p>Crohn's disease should be excluded in patients presenting with Sweet's syndrome and diarrhea. Alternatively, Sweet's syndrome should be considered as a diagnosis when a patient with Crohn's disease develops skin lesions.</p

Routine childhood immunisation during the COVID-19 pandemic in Africa: a benefit-risk analysis of health benefits versus excess risk of SARS-CoV-2 infection.

BACKGROUND: National immunisation programmes globally are at risk of suspension due to the severe health system constraints and physical distancing measures in place to mitigate the ongoing COVID-19 pandemic. We aimed to compare the health benefits of sustaining routine childhood immunisation in Africa with the risk of acquiring severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection through visiting routine vaccination service delivery points. METHODS: We considered a high-impact scenario and a low-impact scenario to approximate the child deaths that could be caused by immunisation coverage reductions during COVID-19 outbreaks. In the high-impact scenario, we used previously reported country-specific child mortality impact estimates of childhood immunisation for diphtheria, tetanus, pertussis, hepatitis B, Haemophilus influenzae type b, Streptococcus pneumoniae, rotavirus, measles, meningitis A, rubella, and yellow fever to approximate the future deaths averted before 5 years of age by routine childhood vaccination during a 6-month COVID-19 risk period without catch-up campaigns. In the low-impact scenario, we approximated the health benefits of sustaining routine childhood immunisation on only the child deaths averted from measles outbreaks during the COVID-19 risk period. We assumed that contact-reducing interventions flattened the outbreak curve during the COVID-19 risk period, that 60% of the population will have been infected by the end of that period, that children can be infected by either vaccinators or during transport, and that upon child infection the whole household will be infected. Country-specific household age structure estimates and age-dependent infection-fatality rates were applied to calculate the number of deaths attributable to the vaccination clinic visits. We present benefit-risk ratios for routine childhood immunisation, with 95% uncertainty intervals (UIs) from a probabilistic sensitivity analysis. FINDINGS: In the high-impact scenario, for every one excess COVID-19 death attributable to SARS-CoV-2 infections acquired during routine vaccination clinic visits, 84 (95% UI 14-267) deaths in children could be prevented by sustaining routine childhood immunisation in Africa. The benefit-risk ratio for the vaccinated children is 85 000 (4900-546 000), for their siblings (60 years) is 96 (14-307). In the low-impact scenario that approximates the health benefits to only the child deaths averted from measles outbreaks, the benefit-risk ratio to the households of vaccinated children is 3 (0-10); if the risk to only the vaccinated children is considered, the benefit-risk ratio is 3000 (182-21 000). INTERPRETATION: The deaths prevented by sustaining routine childhood immunisation in Africa outweigh the excess risk of COVID-19 deaths associated with vaccination clinic visits, especially for the vaccinated children. Routine childhood immunisation should be sustained in Africa as much as possible, while considering other factors such as logistical constraints, staff shortages, and reallocation of resources during the COVID-19 pandemic. FUNDING: Gavi, the Vaccine Alliance; Bill & Melinda Gates Foundation

Phytochromes control metabolic flux, and their action at the seedling stage determines adult plant biomass

Phytochrome (phy) photoreceptors are known to regulate plastic growth responses to vegetation shade. However, recent reports also suggest an important role for phys in carbon resource management, metabolism, and growth. Here, we use 13CO2 labelling patterns in multi-allele phy mutants to investigate the role of phy in the control of metabolic fluxes. We also combine quantitative data of 13C incorporation into protein and cell wall polymers, gas exchange measurements and system modelling to investigate why biomass is decreased in adult multi-allele phy mutants. Phy influences the synthesis of stress metabolites like raffinose and proline, and the accumulation of sugars, possibly through regulating vacuolar sugar transport. Remarkably, despite their modified metabolism and vastly altered architecture, growth rates in adult phy mutants resemble those of wild-type plants. Our results point to delayed seedling growth and smaller cotyledon size as the cause of the adult-stage phy mutant biomass defect. Our data signify a role for phy in metabolic stress physiology, carbon partitioning and illustrate that phy action at the seedling stage sets the trajectory for adult biomass production

Multiple variants of the fungal effector AVR-Pik bind the HMA domain of the rice protein OsHIPP19, providing a foundation to engineer plant defense

Microbial plant pathogens secrete effector proteins, which manipulate the host to promote infection. Effectors can be recognized by plant intracellular nucleotide-binding leucine rich repeat (NLR) receptors, initiating an immune response. The AVR-Pik effector from the rice blast fungus Magnaporthe oryzae is recognized by a pair of rice NLR receptors, Pik-1 and Pik-2. Pik-1 contains a noncanonical integrated heavy-metal associated (HMA) domain, which directly binds AVR-Pik to activate plant defenses. The host targets of AVR-Pik are also HMA-domain-containing proteins, namely heavy-metal associated isoprenylated plant proteins (HIPPs) and heavy metal-Associated plant proteins (HPPs). Here, we demonstrate that one of these targets interacts with a wider set of AVR-Pik variants compared with the Pik-1 HMA domains. We define the biochemical and structural basis of the interaction between AVR-Pik and OsHIPP19 and compare the interaction to that formed with the HMA domain of Pik-1. Using analytical gel filtration and surface plasmon resonance, we show that multiple AVR-Pik variants, including the stealthy variants AVR-PikC and AVR-PikF, which do not interact with any characterized Pik-1 alleles, bind to OsHIPP19 with nanomolar affinity. The crystal structure of OsHIPP19 in complex with AVR-PikF reveals differences at the interface that underpin high-Affinity binding of OsHIPP19-HMA to a wider set of AVR-Pik variants than achieved by the integrated HMA domain of Pik-1. Our results provide a foundation for engi neering the HMA domain of Pik-1 to extend binding to currently unrecognized AVR-Pik variants and expand disease resistance in rice to divergent pathogen strains

p73 Regulates Neurodegeneration and Phospho-Tau Accumulation during Aging and Alzheimer's Disease

SummaryThe genetic mechanisms that regulate neurodegeneration are only poorly understood. We show that the loss of one allele of the p53 family member, p73, makes mice susceptible to neurodegeneration as a consequence of aging or Alzheimer's disease (AD). Behavioral analyses demonstrated that old, but not young, p73+/− mice displayed reduced motor and cognitive function, CNS atrophy, and neuronal degeneration. Unexpectedly, brains of aged p73+/− mice demonstrated dramatic accumulations of phospho-tau (P-tau)-positive filaments. Moreover, when crossed to a mouse model of AD expressing a mutant amyloid precursor protein, brains of these mice showed neuronal degeneration and early and robust formation of tangle-like structures containing P-tau. The increase in P-tau was likely mediated by JNK; in p73+/− neurons, the activity of the p73 target JNK was enhanced, and JNK regulated P-tau levels. Thus, p73 is essential for preventing neurodegeneration, and haploinsufficiency for p73 may be a susceptibility factor for AD and other neurodegenerative disorders

A portable prototype magnetometer to differentiate ischemic and non-ischemic heart disease in patients with chest pain

Background: Magnetocardiography (MCG) is a non-invasive technique used to measure and map cardiac magnetic fields. We describe the predictive performance of a portable prototype magnetometer designed for use in acute and routine clinical settings. We assessed the predictive ability of the measurements derived from the magnetometer for the ruling-out of healthy subjects and patients whose chest pain has a non-ischemic origin from those with ischemic heart disease (IHD). Methods: MCG data were analyzed from a technical performance study, a pilot clinical study, and a young healthy reference group. Participants were grouped to enable differentiation of those with IHD versus non-IHD versus controls: Group A (70 IHD patients); Group B (69 controls); Group C (37 young healthy volunteers). Scans were recorded in an unshielded room. Between-group differences were explored using analysis of variance. The ability of 10 candidate MCG predictors to predict normal/abnormal cases was analyzed using logistic regression. Predictive performance was internally validated using repeated five-fold cross-validation. Results: Three MCG predictors showed a significant difference between patients and age-matched controls (P<0.001); eight predictors showed a significant difference between patients and young healthy volunteers (P<0.001). Logistic regression comparing patients with controls yielded a specificity of 35.0%, sensitivity of 95.4%, and negative predictive value for the ruling-out of IHD of 97.8% (area under the curve 0.78). Conclusion: This analysis represents a preliminary indication that the portable magnetometer can help rule-out healthy subjects and patients whose chest pain has a non-ischemic origin from those with IHD