To perform a systematic review and meta-analysis of prevalence and function of anti-interferon auto-antibodies in acute infectious diseases. We performed a search on the following electronic bibliographic databases: Medline, Embase, Web of Science and Cochrane. Eligible studies generated a systematic review and random effects model meta-analysis of pooled seroprevalence and neutralisation status of anti-interferon auto-antibodies in acute infectious diseases. Thirty-seven studies including 12,629 individuals with SARS-CoV-2 infection were analysed. There are insufficient data for meta-analyses of auto-antibodies in non-SARS-CoV-2 infectious diseases, with crude seroprevalence of auto-antibodies varying widely (0.0–77.0

BACKGROUND:Immunocompromised travellers (ICTs) face greater infectious and non-infectious travel-associated risks than their immunocompetent counterparts. Increasing travel and emergence of novel immunosuppressants poses great challenges for travel medicine practitioners to confidently provide up-to-date evidence-based risk management advice and pre-travel care for ICTs.METHODS:We reviewed the records of ICTs attending the London Hospital for Tropical Diseases (HTD) Travel Clinic between 1st April 2019 and 30th April 2020 with the aim to describe demographic and travel characteristics, type, and severity of immunocompromise, the degree of risk associated with intended travel and evaluate travel advice.RESULTS:Of the 193 ICTs identified, immunocompromise was due to physiological reasons (42%), chronic infection (17.1%) and immunosuppressive therapy (16.6%). Median age was 38 (range 9 months to 84 years) and male to female ratio 0.75 (83:110). Travel was intended to 80 countries for a median of 16 days (range 2 to 3167), predominantly for leisure (53%), non-medical work (17%) and visiting friends and relatives (12%). Live vaccine safety dominated discussion in the pre-travel consultation. Existing guidelines arguably fell short in dealing with travel risks associated with hyper-specific conditions, targeted immunosuppressants and non-vaccine preventable infections.CONCLUSIONS:Our cohort represents a wide spectrum of immunocompromise, for whom we arguably need more measurable ways to approach travel-associated risks. We propose prospective qualitative participatory research to inform our unit of the priorities of ICTs in the pre-travel consultation. We further recommend the formation of a repository of specialists and formulary of complex cases to direct subsequent informative systematic review and prospective risk studies.

As large language models (LLMs) expand and become more advanced, so do the natural language processing capabilities of conversational AI, or "chatbots". OpenAI's recent release, ChatGPT, uses a transformer-based model to enable human-like text generation and question-answering on general domain knowledge, while a healthcare-specific Large Language Model (LLM) such as GatorTron has focused on the real-world healthcare domain knowledge. As LLMs advance to achieve near human-level performances on medical question and answering benchmarks, it is probable that Conversational AI will soon be developed for use in healthcare. In this article we discuss the potential and compare the performance of two different approaches to generative pretrained transformers-ChatGPT, the most widely used general conversational LLM, and Foresight, a GPT (generative pretrained transformer) based model focused on modelling patients and disorders. The comparison is conducted on the task of forecasting relevant diagnoses based on clinical vignettes. We also discuss important considerations and limitations of transformer-based chatbots for clinical use.

Objectives To quantify reader agreement for the British Society of Thoracic Imaging (BSTI) diagnostic and severity classification for COVID-19 on chest radiographs (CXR), in particular agreement for an indeterminate CXR that could instigate CT imaging, from single and paired images. Methods Twenty readers (four groups of five individuals)—consultant chest (CCR), general consultant (GCR), and specialist registrar (RSR) radiologists, and infectious diseases clinicians (IDR)—assigned BSTI categories and severity in addition to modified Covid-Radiographic Assessment of Lung Edema Score (Covid-RALES), to 305 CXRs (129 paired; 2 time points) from 176 guideline-defined COVID-19 patients. Percentage agreement with a consensus of two chest radiologists was calculated for (1) categorisation to those needing CT (indeterminate) versus those that did not (classic/probable, non-COVID-19); (2) severity; and (3) severity change on paired CXRs using the two scoring systems. Results Agreement with consensus for the indeterminate category was low across all groups (28–37%). Agreement for other BSTI categories was highest for classic/probable for the other three reader groups (66–76%) compared to GCR (49%). Agreement for normal was similar across all radiologists (54–61%) but lower for IDR (31%). Agreement for a severe CXR was lower for GCR (65%), compared to the other three reader groups (84–95%). For all groups, agreement for changes across paired CXRs was modest. Conclusion Agreement for the indeterminate BSTI COVID-19 CXR category is low, and generally moderate for the other BSTI categories and for severity change, suggesting that the test, rather than readers, is limited in utility for both deciding disposition and serial monitoring. Key Points • Across different reader groups, agreement for COVID-19 diagnostic categorisation on CXR varies widely. • Agreement varies to a degree that may render CXR alone ineffective for triage, especially for indeterminate cases. • Agreement for serial CXR change is moderate, limiting utility in guiding management.

Background: The scale of the 2022 global monkeypox outbreak has been unprecedented. In under six-months, non-endemic countries have reported over 67,000 cases of a disease that had previously been rare outside of Africa. Mortality has been reported as rare but hospitalisation relatively common. We aimed to describe the clinical and laboratory characteristics and outcomes of individuals hospitalised with monkeypox and associated complications, including tecovirimat recipients. Methods: Sixteen hospitals from the Specialist and High Consequence Infectious Diseases Network for Monkeypox contributed to this retrospective service evaluation of individuals admitted to those sites between 6th May and 3rd August 2022. Electronic records were used to extract routinely available deidentified clinical and pathology data. Findings: 156 individuals were hospitalised with complicated monkeypox during the study period. 153 were men with a median age of 35 years (range 19-64). 47 (30%) were living with HIV with a median CD4 count of 510 cells/mm3 (IQR 349-828). Rectal or perianal pain (including proctitis) was the most common indication for hospital admission. Severe pain and secondary bacterial infection were reported in 89 (57%) and 82 (53%) individuals. Median admission duration was 5 days (IQR 2-9). Ten individuals required surgery. Two cases of encephalitis were reported. 38 (24%) individuals received tecovirimat with early cessation in 4 cases. Interpretation: Although life-threatening monkeypox appears rare in hospitalised populations during the current outbreak, severe monkeypox and associated complications can occur in immunocompetent individuals. Analgesia and management of superimposed bacterial infection are priorities for hospitalised patients.Funding: NoneDeclaration of Interest: On behalf of Leeds Teaching Hospitals Trust I can confirm that PL/ BH have no competing interests.Ethical Approval: Each contributing centre followed its local policy for reviewing a proposed service evaluation and a request to submit deidentified data, extracted from inpatient records, for the purposes of a network analysis, without obtaining specific consent from individual patients. Localrecords were accessed only by clinicians involved in the care of hospitalised cases at thecentre. Where local policy required written approval or registration of a service evaluation,this was obtained by the respective centre. Deidentified data were securely transferred byeach centre to the coordinating site (the Royal Free Hospital) for collation and analysis.

The COVID-19 pandemic has necessitated rapid adaptation of healthcare providers to new clinical and logistical challenges. Following identification of high levels of emergency department (ED) reattendance among patients with suspected COVID-19 at our centre, we piloted a rapid remote follow-up service for this patient group. We present our service framework and evaluation of our pilot cohort of 192 patients. We followed up patients by telephone within 36 hours of their ED attendance. Pulse oximetry was used for remote monitoring of a subset of patients. Patients required between one and six consecutive telephone assessments, dependent on illness severity, and 23 patients were recalled for in-person assessment. Approximately half of patients with confirmed or probable COVID-19 required onward referral for respiratory follow-up. This framework reduced unplanned ED reattendances in comparison with a retrospective comparator cohort (4.7% from 22.6%). We reproduced these findings in a validation cohort with a high prevalence of acute COVID-19, managed through the clinic in September-October 2020, where we identified an unplanned ED reattendance rate of 5.2%. We propose that rapid remote follow-up is a mechanism by which ambulatory patients can be clinically supported during the acute phase of illness, with benefits both to patient care and to health service resilience.

Background A subset of patients with severe COVID-19 develop a hyperinflammatory syndrome, which might contribute to morbidity and mortality. This study explores a specific phenotype of COVID-19-associated hyperinflammation (COV-HI), and its associations with escalation of respiratory support and survival. Methods In this retrospective cohort study, we enrolled consecutive inpatients (aged >= 18 years) admitted to University College London Hospitals and Newcastle upon Tyne Hospitals in the UK with PCR-confirmed COVID-19 during the first wave of community-acquired infection. Demographic data, laboratory tests, and clinical status were recorded from the day of admission until death or discharge, with a minimum follow-up time of 28 days. We defined COV-HI as a C-reactive protein concentration greater than 150 mg/L or doubling within 24 h from greater than 50 mg/L, or a ferritin concentration greater than 1500 mu g/L. Respiratory support was categorised as oxygen only, non-invasive ventilation, and intubation. Initial and repeated measures of hyperinflammation were evaluated in relation to the next-day risk of death or need for escalation of respiratory support (as a combined endpoint), using a multi-level logistic regression model. Findings We included 269 patients admitted to one of the study hospitals between March 1 and March 31, 2020, among whom 178 (66%) were eligible for escalation of respiratory support and 91 (34%) patients were not eligible. Of the whole cohort, 90 (33%) patients met the COV-HI criteria at admission. Despite having a younger median age and lower median Charlson Comorbidity Index scores, a higher proportion of patients with COV-HI on admission died during follow-up (36 [40%] of 90 patients) compared with the patients without COV-HI on admission (46 [26%] of 179). Among the 178 patients who were eligible for full respiratory support, 65 (37%) met the definition for COV-HI at admission, and 67 (74%) of the 90 patients whose respiratory care was escalated met the criteria by the day of escalation. Meeting the COV-HI criteria was significantly associated with the risk of next-day escalation of respiratory support or death (hazard ratio 2.24 [95% CI 1.62-2.87]) after adjustment for age, sex, and comorbidity. Interpretation Associations between elevated inflammatory markers, escalation of respiratory support, and survival in people with COVID-19 indicate the existence of a high-risk inflammatory phenotype. COV-HI might be useful to stratify patient groups in trial design.

The number of proposed prognostic models for coronavirus disease 2019 (COVID-19) is growing rapidly, but it is unknown whether any are suitable for widespread clinical implementation.We independently externally validated the performance of candidate prognostic models, identified through a living systematic review, among consecutive adults admitted to hospital with a final diagnosis of COVID-19. We reconstructed candidate models as per original descriptions and evaluated performance for their original intended outcomes using predictors measured at the time of admission. We assessed discrimination, calibration and net benefit, compared to the default strategies of treating all and no patients, and against the most discriminating predictors in univariable analyses.We tested 22 candidate prognostic models among 411 participants with COVID-19, of whom 180 (43.8%) and 115 (28.0%) met the endpoints of clinical deterioration and mortality, respectively. Highest areas under receiver operating characteristic (AUROC) curves were achieved by the NEWS2 score for prediction of deterioration over 24 h (0.78, 95% CI 0.73–0.83), and a novel model for prediction of deterioration <14 days from admission (0.78, 95% CI 0.74–0.82). The most discriminating univariable predictors were admission oxygen saturation on room air for in-hospital deterioration (AUROC 0.76, 95% CI 0.71–0.81), and age for in-hospital mortality (AUROC 0.76, 95% CI 0.71–0.81). No prognostic model demonstrated consistently higher net benefit than these univariable predictors, across a range of threshold probabilities.Admission oxygen saturation on room air and patient age are strong predictors of deterioration and mortality among hospitalised adults with COVID-19, respectively. None of the prognostic models evaluated here offered incremental value for patient stratification to these univariable predictors.

BACKGROUND:The COVID-19 pandemic presents a significant infection prevention and control challenge. The admission of large numbers of patients with suspected COVID-19 disease risks overwhelming the capacity to protect other patients from exposure. The delay between clinical suspicion and confirmatory testing adds to the complexity of the problem. METHODS:We implemented a triage tool aimed at minimizing hospital-acquired COVID-19 particularly in patients at risk of severe disease. Patients were allocated to triage categories defined by likelihood of COVID-19 and risk of a poor outcome. Category A (low-likelihood; high-risk), B (high-likelihood; high-risk), C (high-likelihood; low-risk) and D (low-likelihood; low-risk). This determined the order of priority for isolation in single-occupancy rooms with Category A the highest. Patients in other groups were cohorted when isolation capacity was limited with additional interventions to reduce transmission. RESULTS:Ninety-three patients were evaluated with 79 (85%) receiving a COVID-19 diagnosis during their admission. Of those without a COVID-19 diagnosis: 10 were initially triaged to Category A; 0 to B; 1 to C and 4 to D. All high-risk patients requiring isolation were, therefore, admitted to single-occupancy rooms and protected from exposure. Twenty-eight (30%) suspected COVID-19 patients were evaluated to be low risk (groups C and D) and eligible for cohorting. No symptomatic hospital-acquired infections were detected in the cohorted patients. DISCUSSION:Application of a clinical triage tool to guide isolation and cohorting decisions may reduce the risk of hospital-acquired transmission of COVID-19 especially to individuals at the greatest of risk of severe disease.

Background: Acute bacterial meningitis (ABM) in adults is associated with a mortality that may exceed 30%. Immunization programs have reduced the global burden; in the UK, declining incidence but persistently high mortality and morbidity mean that clinicians must remain vigilant. Sources of data: A systematic electronic literature search of PubMed was performed to identify all ABM literature published within the past 5 years. Areas of agreement and controversy: Clinical features cannot reliably distinguish between ABM and other important infectious and non-infectious aetiologies. Prompt investigation and empirical treatment are imperative. Lumbar puncture (LP) and cerebrospinal fluid microscopy, biochemistry and culture remain the mainstay of diagnosis, but molecular techniques are increasingly useful. The 2016 UK joint specialist societies' guideline provides expert recommendations for the management of ABM, yet published data suggest clinical care delivered in the UK is frequently not adherent. Anxiety regarding risk of cerebral herniation following LP, unnecessary neuroimaging, underutilization of molecular diagnostics and suboptimal uptake of adjunctive corticosteroids compromise management. Growing points: There is increasing recognition that current antibiotic regimens and adjunctive therapies alone are insufficient to reduce the mortality and morbidity associated with ABM. Areas timely for developing research: Research should be focused on optimization of vaccines (e.g. pneumococcal conjugate vaccines with extended serotype coverage), targeting groups at risk for disease and reservoirs for transmission; improving adherence to management guidelines; development of new faster, more accurate diagnostic platforms (e.g. novel point-of-care molecular diagnostics); and development of new adjunctive therapies (aimed at the host-inflammatory response and bacterial virulence factors).

Pre-registrar experience of the duty medical registrar (DMR) role is limited to opportunistic encounters, often in under-resourced settings with a rota gap. A previous survey has showed that 44% of core medical trainees (CMTs) feel unprepared to take on the role as DMR.1 The role is perceived by some early trainees to be ‘impossible’, requiring ‘superhero’ skills.2 Medical registrars and consultants themselves acknowledge the complexity of juggling a high workload, providing leadership and dealing with acutely unwell patients.3,4 These perceptions and lack of experiential DMR training could contribute to a decline in acute medical specialty recruitment. Further, trainees who eventually take on the role often experience a ‘trial by fire’, leading to undue stress and anxiety. The UCLH ‘Ready to Reg’ programme aims to provide CMTs with hands-on field training as a DMR under direct guidance of another medical registrar.

Background: Providing medical care for non-communicable diseases (NCDs) in rural sub-Saharan Africa has proved to be difficult because of poor treatment adherence and frequent loss to follow-up (LTFU). The reasons for this are poorly understood.Objective: To investigate LTFU among patients with two different but common NCDs who attended rural Ethiopian health centres.Method: The study was based in five health centres in southern Ethiopia with established NCD clinics run by nurses and health officers. Patients with epilepsy or hypertension who were lost to follow-up and non-LTFU comparison patients were identified and traced; a questionnaire was administered enquiring about the reasons for LTFU.Results: Of the 147 LTFU patients successfully located, 62 had died, moved away or were attending other medical facilities. The remaining 85 patients were compared with 211 non-LFTU patients. The major factors associated with LTFU were distance from the clinic, associated costs and a preference for traditional treatments, together with a misunderstanding of the nature of NCD management.Conclusions: The delivery of affordable care closer to the patients' homes has the greatest potential to address the problem of LTFU. Also needed are increased levels of patient education and interaction with traditional healers to explain the nature of NCDs and the need for life-long management.

Human African trypanosomiasis has not been reported in Nigeria since 2012. Nevertheless, limitations of current surveillance programs mean that undetected infections may persist. We report a recent case of stage 2 trypanosomiasis caused by Trypanosoma brucei gambiense acquired in Nigeria and imported into the United Kingdom.

A 62 year-old, previously well, Caucasian woman presented to hospital with an acute onset, moderate intensity headache after lifting a heavy object while bending down. The headache lasted 15 minutes and was bilateral over the vertex, without photophobia, motion sensitivity, nausea or autonomic

The Bill & Melinda Gates Foundation is a major contributor to global health; its influence on international health policy and the design of global health programmes and initiatives is profound. Although the foundation's contribution to global health generally receives acclaim, fairly little is known about its grant-making programme. We undertook an analysis of 1094 global health grants awarded between January, 1998, and December, 2007. We found that the total value of these grants was US$8·95 billion, of which $5·82 billion (65%) was shared by only 20 organisations. Nevertheless, a wide range of global health organisations, such as WHO, the GAVI Alliance, the World Bank, the Global Fund to Fight AIDS, Tuberculosis and Malaria, prominent universities, and non-governmental organisations received grants. $3·62 billion (40% of all funding) was given to supranational organisations. Of the remaining amount, 82% went to recipients based in the USA. Just over a third ($3·27 billion) of funding was allocated to research and development (mainly for vaccines and microbicides), or to basic science research. The findings of this report raise several questions about the foundation's global health grant-making programme, which needs further research and assessment.