Using ISARIC 4C mortality score to predict dynamic changes in mortality risk in COVID-19 patients during hospital admission.

As SARS-CoV-2 infections continue to cause hospital admissions around the world, there is a continued need to accurately assess those at highest risk of death to guide resource use and clinical management. The ISARIC 4C mortality score provides mortality risk prediction at admission to hospital based on demographic and physiological parameters. Here we evaluate dynamic use of the 4C score at different points following admission. Score components were extracted for 6,373 patients admitted to Barts Health NHS Trust hospitals between 1st August 2020 and 19th July 2021 and total score calculated every 48 hours for 28 days. Area under the receiver operating characteristic (AUC) statistics were used to evaluate discrimination of the score at admission and subsequent inpatient days. Patients who were still in hospital at day 6 were more likely to die if they had a higher score at day 6 than others also still in hospital who had the same score at admission. Discrimination of dynamic scoring in those still in hospital was superior with the area under the curve 0.71 (95% CI 0.69-0.74) at admission and 0.82 (0.80-0.85) by day 8. Clinically useful changes in the dynamic parts of the score are unlikely to be associated with subject-level measurements. Dynamic use of the ISARIC 4C score is likely to provide accurate and timely information on mortality risk during a patient's hospital admission

Exploring the views of infection consultants in England on a novel delinked funding model for antimicrobials: the SMASH study

OBJECTIVES: A novel 'subscription-type' funding model was launched in England in July 2022 for ceftazidime/avibactam and cefiderocol. We explored the views of infection consultants on important aspects of the delinked antimicrobial funding model. METHODS: An online survey was sent to all infection consultants in NHS acute hospitals in England. RESULTS: The response rate was 31.2% (235/753). Most consultants agreed the model is a welcome development (69.8%, 164/235), will improve treatment of drug-resistant infections (68.5%, 161/235) and will stimulate research and development of new antimicrobials (57.9%, 136/235). Consultants disagreed that the model would lead to reduced carbapenem use and reported increased use of cefiderocol post-implementation. The presence of an antimicrobial pharmacy team, requirement for preauthorization by infection specialists, antimicrobial stewardship ward rounds and education of infection specialists were considered the most effective antimicrobial stewardship interventions. Under the new model, 42.1% (99/235) of consultants would use these antimicrobials empirically, if risk factors for antimicrobial resistance were present (previous infection, colonization, treatment failure with carbapenems, ward outbreak, recent admission to a high-prevalence setting).Significantly higher insurance and diversity values were given to model antimicrobials compared with established treatments for carbapenem-resistant infections, while meropenem recorded the highest enablement value. Use of both 'subscription-type' model drugs for a wide range of infection sites was reported. Respondents prioritized ceftazidime/avibactam for infections by bacteria producing OXA-48 and KPC and cefiderocol for those producing MBLs and infections with Stenotrophomonas maltophilia, Acinetobacter spp. and Burkholderia cepacia. CONCLUSIONS: The 'subscription-type' model was viewed favourably by infection consultants in England

Exploring the views of infection consultants in England on a novel delinked funding model for antimicrobials: the SMASH study

OBJECTIVES: A novel ‘subscription-type’ funding model was launched in England in July 2022 for ceftazidime/avibactam and cefiderocol. We explored the views of infection consultants on important aspects of the delinked antimicrobial funding model. METHODS: An online survey was sent to all infection consultants in NHS acute hospitals in England. RESULTS: The response rate was 31.2% (235/753). Most consultants agreed the model is a welcome development (69.8%, 164/235), will improve treatment of drug-resistant infections (68.5%, 161/235) and will stimulate research and development of new antimicrobials (57.9%, 136/235). Consultants disagreed that the model would lead to reduced carbapenem use and reported increased use of cefiderocol post-implementation. The presence of an antimicrobial pharmacy team, requirement for preauthorization by infection specialists, antimicrobial stewardship ward rounds and education of infection specialists were considered the most effective antimicrobial stewardship interventions. Under the new model, 42.1% (99/235) of consultants would use these antimicrobials empirically, if risk factors for antimicrobial resistance were present (previous infection, colonization, treatment failure with carbapenems, ward outbreak, recent admission to a high-prevalence setting). Significantly higher insurance and diversity values were given to model antimicrobials compared with established treatments for carbapenem-resistant infections, while meropenem recorded the highest enablement value. Use of both ‘subscription-type’ model drugs for a wide range of infection sites was reported. Respondents prioritized ceftazidime/avibactam for infections by bacteria producing OXA-48 and KPC and cefiderocol for those producing MBLs and infections with Stenotrophomonas maltophilia, Acinetobacter spp. and Burkholderia cepacia. CONCLUSIONS: The ‘subscription-type’ model was viewed favourably by infection consultants in England

The Future of Precision Medicine : Potential Impacts for Health Technology Assessment

Objective Precision medicine allows health care interventions to be tailored to groups of patients based on their disease susceptibility, diagnostic or prognostic information or treatment response. We analyse what developments are expected in precision medicine over the next decade and consider the implications for health technology assessment (HTA) agencies. Methods We perform a pragmatic review of the literature on the health economic challenges of precision medicine, and conduct interviews with representatives from HTA agencies, research councils and researchers from a variety of fields, including digital health, health informatics, health economics and primary care research. Results Three types of precision medicine are highlighted as likely to emerge in clinical practice and impact upon HTA agencies: complex algorithms, digital health applications and ‘omics’-based tests. Defining the scope of an evaluation, identifying and synthesizing the evidence and developing decision analytic models will more difficult when assessing more complex and uncertain treatment pathways. Stratification of patients will result in smaller subgroups, higher standard errors and greater decision uncertainty. Equity concerns may present in instances where biomarkers correlate with characteristics such as ethnicity, whilst fast-paced innovation may reduce the shelf-life of guidance and necessitate more frequent reviewing. Discussion Innovation in precision medicine promises substantial benefits to patients, but will also change the way in which some health services are delivered and evaluated. As biomarker discovery accelerates and AI-based technologies emerge, the technical expertise and processes of HTA agencies will need to adapt if the objective of value for money is to be maintained

Interventions to reduce inequalities in vaccine uptake in children and adolescents aged <19 years: a systematic review.

: In high-income countries, substantial differences exist in vaccine uptake relating to socioeconomic status, gender, ethnic group, geographic location and religious belief. This paper updates a 2009 systematic review on effective interventions to decrease vaccine uptake inequalities in light of new technologies applied to vaccination and new vaccine programmes (eg, human papillomavirus in adolescents). : We searched MEDLINE, Embase, ASSIA, The Campbell Collaboration, CINAHL, The Cochrane Database of Systematic Reviews, Eppi Centre, Eric and PsychINFO for intervention, cohort or ecological studies conducted at primary/community care level in children and young people from birth to 19 years in OECD countries, with vaccine uptake or coverage as outcomes, published between 2008 and 2015. : The 41 included studies evaluated complex multicomponent interventions (n=16), reminder/recall systems (n=18), outreach programmes (n=3) or computer-based interventions (n=2). Complex, locally designed interventions demonstrated the best evidence for effectiveness in reducing inequalities in deprived, urban, ethnically diverse communities. There is some evidence that postal and telephone reminders are effective, however, evidence remains mixed for text-message reminders, although these may be more effective in adolescents. Interventions that escalated in intensity appeared particularly effective. Computer-based interventions were not effective. Few studies targeted an inequality specifically, although several reported differential effects by the ethnic group. : Locally designed, multicomponent interventions should be used in urban, ethnically diverse, deprived populations. Some evidence is emerging for text-message reminders, particularly in adolescents. Further research should be conducted in the UK and Europe with a focus on reducing specific inequalities.<br/

Medical education in difficult circumstances: analysis of the experience of clinical medical students following the new innovative medical curriculum in Aksum, rural Ethiopia

Abstract Background In 2012, 12 medical schools were opened in Ethiopia to tackle the significant shortage of doctors. This included Aksum School of Medicine situated in Aksum, a rural town in Northern Ethiopia. The new Innovative Medical Curriculum (NIMC) is a four-year programme designed by the Ethiopian Federal Ministries of Health and Education. The curriculum is designed to train biomedical science graduates to become doctors in 4 years, with a focus on the healthcare needs of rural people living in poverty. Methods This research was conducted at Aksum School of Medicine and included two hospitals (Aksum Referral Hospital and St Mary’s District Hospital). This study focused on medical students during their clinical years across multiple specialities (61 Clerkship 1 students and 13 Clerkship 2 students). We used primarily qualitative research methods supplemented with quantitative measures. There were 3 stages of data collection over a 1 month period, this included qualitative group interviews, direct observation of students in a clinical setting and direct observation of skills sessions followed by a questionnaire on the sessions. We analysed the data by reconstructing the student experience and comparing it with the NIMC. Results The proposed typical week set out in the NIMC tended to differ from the real clinical experience of these students. Through qualitative group interview and direct observation of teaching, the main theme that was consistent throughout was the lack of doctors with specialist postgraduate training. Clinical need often took priority over education. However, students enjoyed taking early responsibility and gaining practical experience. Through direct observation of skills sessions and short questionnaires, these sessions were highly valuable to the students and they felt confident in carrying out the taught procedures in the future. Conclusions The combination of poorly resourced hospitals and lack of specialist doctors provides a challenging environment for medical students to learn. However, it is a unique clinical experience that is rarely seen in developed countries and facilitates the acquirement of skills from an early stage. Supervision and specialist input is fundamental in enabling students to learn and this is a key area that was lacking in the students’ clinical experience

The development and activity-dependent expression of aggrecan in the cat visual cortex

The Cat-301 monoclonal antibody identifies aggrecan, a chondroitin sulfate proteoglycan in the cat visual cortex and dorsal lateral geniculate nucleus (dLGN). During development, aggrecan expression increases in the dLGN with a time course that matches the decline in plasticity. Moreover, examination of tissue from selectively visually deprived cats shows that expression is activity dependent, suggesting a role for aggrecan in the termination of the sensitive period. Here, we demonstrate for the first time that the onset of aggrecan expression in area 17 also correlates with the decline in experience-dependent plasticity in visual cortex and that this expression is experience dependent. Dark rearing until 15 weeks of age dramatically reduced the density of aggrecan-positive neurons in the extragranular layers, but not in layer IV. This effect was reversible as dark-reared animals that were subsequently exposed to light showed normal numbers of Cat-301-positive cells. The reduction in aggrecan following certain early deprivation regimens is the first biochemical correlate of the functional changes to the γ-aminobutyric acidergic system that have been reported following early deprivation in cats