Post-kala-azar dermal leishmaniasis (PKDL) drug efficacy study landscape: A systematic scoping review of clinical trials and observational studies to assess the feasibility of establishing an individual participant-level data (IPD) platform.

BACKGROUND: Post-kala-azar dermal leishmaniasis (PKDL) is a dermatosis which can occur after successful treatment of visceral leishmaniasis (VL) and is a public health problem in VL endemic areas. We conducted a systematic scoping review to assess the characteristics of published PKDL clinical studies, understand the scope of research and explore the feasibility and value of developing a PKDL individual patient data (IPD) platform. METHODS: A systematic review of published literature was conducted to identify PKDL clinical studies by searching the following databases: PubMed, Scopus, Ovid Embase, Web of Science Core Collection, WHO Global Index Medicus, PASCAL, Clinicaltrials.gov, Ovid Global Health, Cochrane Database and CENTRAL, and the WHO International Clinical Trials Registry Platform. Only prospective studies in humans with PKDL diagnosis, treatment, and follow-up measurements between January 1973 and March 2023 were included. Extracted data includes variables on patient characteristics, treatment regimens, diagnostic methods, geographical locations, efficacy endpoints, adverse events and statistical methodology. RESULTS: A total of 3,418 records were screened, of which 56 unique studies (n = 2,486 patients) were included in this review. Out of the 56 studies, 36 (64.3%) were from India (1983-2022), 12 (21.4%) from Sudan (1992-2021), 6 (10.7%) were from Bangladesh (1991-2019), and 2 (3.6%) from Nepal (2001-2007). Five (8.9%) studies were published between 1981-1990 (n = 193 patients), 10 (17.9%) between 1991-2000 (n = 230 patients), 10 (17.9%) between 2001-2010 (n = 198 patients), and 31 (55.4%) from 2011 onwards (n = 1,865 patients). Eight (14.3%) were randomised clinical trials, and 48 (85.7%) were non-randomised studies. The median post-treatment follow-up duration was 365 days (range: 90-540 days) in 8 RCTs and 360 days (range: 28-2,373 days) in 48 non-randomised studies. Disease diagnosis was based on clinical criterion in 3 (5.4%) studies, a mixture of clinical and parasitological methods in 47 (83.9%) and was unclear in 6 (10.7%) studies. Major drugs used for treatment were miltefosine (n = 636 patients), liposomal amphotericin B (L-AmB) (n = 508 patients), and antinomy regimens (n = 454 patients). Ten other drug regimens were tested in 270 patients with less than 60 patients per regimen. CONCLUSIONS: Our review identified studies with very limited sample size for the three major drugs (miltefosine, L-AmB, and pentavalent antimony), while the number of patients combined across studies suggest that the IPD platform would be valuable. With the support of relevant stakeholders, the global PKDL community and sufficient financing, a PKDL IPD platform can be realised. This will allow for exploration of different aspects of treatment safety and efficacy, which can potentially guide future healthcare decisions and clinical practices.

Systematic Review and Geospatial Modeling of Molecular Markers of Resistance to Artemisinins and Sulfadoxine-Pyrimethamine in Plasmodium falciparum in India.

Surveillance for genetic markers of resistance can provide valuable information on the likely efficacy of antimalarials but needs to be targeted to ensure optimal use of resources. We conducted a systematic search and review of publications in seven databases to compile resistance marker data from studies in India. The sample collection from the studies identified from this search was conducted between 1994 and 2020, and these studies were published between 1994 and 2022. In all, Plasmodium falciparum Kelch13 (PfK13), P. falciparum dihydropteroate synthase, and P. falciparum dihydrofolate reductase (PfDHPS) genotype data from 2,953, 4,148, and 4,222 blood samples from patients with laboratory-confirmed malaria, respectively, were extracted from these publications and uploaded onto the WorldWide Antimalarial Resistance Network molecular surveyors. These data were fed into hierarchical geostatistical models to produce maps with a predicted prevalence of the PfK13 and PfDHPS markers, and of the associated uncertainty. Zones with a predicted PfDHPS 540E prevalence of >15% were identified in central, eastern, and northeastern India. The predicted prevalence of PfK13 mutants was nonzero at only a few locations, but were within or adjacent to the zones with >15% prevalence of PfDHPS 540E. There may be a greater probability of artesunate-sulfadoxine-pyrimethamine failures in these regions, but these predictions need confirmation. This work can be applied in India and elsewhere to help identify the treatments most likely to be effective for malaria elimination.

Stakeholder perspectives towards diagnostic artificial intelligence: a co-produced qualitative evidence synthesis.

Background: Diagnosis is a cornerstone of medical practice. Worldwide, there is increased demand for diagnostic services, exacerbating workforce shortages. Artificial intelligence (AI) technologies may improve diagnostic efficiency, accuracy, and access. Understanding stakeholder perspectives is key to informing implementation of complex interventions. We systematically reviewed the literature on stakeholder perspectives on diagnostic AI, including all English-language peer-reviewed primary qualitative or mixed-methods research. Methods: We searched PubMed, Ovid MEDLINE/Embase, Scopus, CINAHL and Web of Science (22/2/2023 and updated 8/2/2024). The Critical Appraisal Skills Programme Checklist informed critical appraisal. We used a 'best-fit' framework approach for analysis, using the Non-adoption, Abandonment, Scale-up, Spread, Sustainability (NASSS) framework. This study was pre-registered (PROSPERO CRD42022313782). Findings: We screened 16,577 articles and included 44. 689 participants were interviewed, and 402 participated in focus groups. Four stakeholder groups were described: patients, clinicians, researchers and healthcare leaders. We found an under-representation of patients, researchers and leaders across articles. We summarise the differences and relationships between each group in a conceptual model, hinging on the establishment of trust, engagement and collaboration. We present a modification of the NASSS framework, tailored to diagnostic AI. Interpretation: We provide guidance for future research and implementation of diagnostic AI, highlighting the importance of representing all stakeholder groups. We suggest that implementation strategies consider how any proposed software fits within the extended NASSS-AI framework, and how stakeholder priorities and concerns have been addressed. Funding: RK is supported by an NIHR Doctoral Research Fellowship grant (NIHR302562), which funded patient and public involvement activities, and access to Covidence.

The ethical challenges of diversifying genomic data: A qualitative evidence synthesis.

This article aims to explore the ethical issues arising from attempts to diversify genomic data and include individuals from underserved groups in studies exploring the relationship between genomics and health. We employed a qualitative synthesis design, combining data from three sources: 1) a rapid review of empirical articles published between 2000 and 2022 with a primary or secondary focus on diversifying genomic data, or the inclusion of underserved groups and ethical issues arising from this, 2) an expert workshop and 3) a narrative review. Using these three sources we found that ethical issues are interconnected across structural factors and research practices. Structural issues include failing to engage with the politics of knowledge production, existing inequities, and their effects on how harms and benefits of genomics are distributed. Issues related to research practices include a lack of reflexivity, exploitative dynamics and the failure to prioritise meaningful co-production. Ethical issues arise from both the structure and the practice of research, which can inhibit researcher and participant opportunities to diversify data in an ethical way. Diverse data are not ethical in and of themselves, and without being attentive to the social, historical and political contexts that shape the lives of potential participants, endeavours to diversify genomic data run the risk of worsening existing inequities. Efforts to construct more representative genomic datasets need to develop ethical approaches that are situated within wider attempts to make the enterprise of genomics more equitable.

Nocturnal oxygen therapy in obstructive sleep apnoea: a systematic review and meta-analysis.

Obstructive sleep apnoea is characterised by recurrent reduction of airflow during sleep leading to intermittent hypoxia. Continuous positive airway pressure is the first-line treatment but is limited by poor adherence. Nocturnal oxygen therapy may be an alternative treatment for obstructive sleep apnoea but its effects remain unclear. This meta-analysis evaluates the effects of nocturnal oxygen therapy on both obstructive sleep apnoea severity and blood pressure.A literature search was performed based on the Preferred Reporting Items for Systematic Review and Meta-analysis guidelines. Peer-reviewed, randomised studies that compared the effect of nocturnal oxygen therapy to sham in obstructive sleep apnoea patients were included. The main outcomes were the apnoea-hypopnoea index and systolic and diastolic blood pressure.The search strategy yielded 1295 citations. Nine studies with 502 participants were included. When nocturnal oxygen therapy was compared to sham/air, it significantly reduced the apnoea-hypopnoea index (mean difference (MD) -15.17 events·h-1, 95% CI -19.95- -10.38 events·h-1, p<0.00001). Nocturnal oxygen therapy had no significant effect on blood pressure at follow-up without adjustment for baseline values, but did, where available, significantly attenuate the change in blood pressure from baseline to follow-up for both systolic blood pressure (MD -2.79 mmHg, 95% CI -5.45- -0.14 mmHg, p=0.040) and diastolic blood pressure (MD -2.20 mmHg, 95% CI -3.83- -0.57 mmHg, p=0.008).Nocturnal oxygen therapy reduced the apnoea-hypopnoea index severity and the change in (but not absolute) systolic and diastolic blood pressure, compared to sham. This suggests that nocturnal oxygen therapy may be a treatment option for obstructive sleep apnoea. Further studies with longer-term follow-up and standardised measurements are needed.

Understanding psychosis complexity through a syndemic framework: A systematic review.

Psychotic conditions pose significant challenges due to their complex aetiology and impact on individuals and communities. Syndemic theory offers a promising framework to understand the interconnectedness of various health and social problems in the context of psychosis. This systematic review aims to examine existing literature on testing whether psychosis is better understood as a component of a syndemic. We conducted a systematic search of 7 databases, resulting in the inclusion of five original articles. Findings from these studies indicate a syndemic characterized by the coexistence of various health and social conditions, are associated with a greater risk of psychosis, adverse health outcomes, and disparities, especially among ethnic minorities and deprived populations. This review underscores the compelling need for a new paradigm and datasets that can investigate how psychosis emerges in the context of a syndemic, ultimately guiding more effective preventive and care interventions as well as policies to improve the health of marginalised communities living in precarity.

Development and application of the direct mycobacterial growth inhibition assay: a systematic review.

Introduction: First described by Wallis et al. in 2001 for the assessment of TB drugs, the direct mycobacterial growth inhibition assay (MGIA) offers a tractable ex vivo tool measuring the combined influences of host immunity, strain virulence and intervention effects. Over the past 13 years, we have led efforts to adapt the direct MGIA for the assessment of TB vaccines including optimisation, harmonisation and validation of BCG vaccine-induced responses as a benchmark, as well as assay transfer to institutes worldwide. Methods: We have performed a systematic review on the primary published literature describing the development and applications of the direct MGIA from 2001 to June 2023 in accordance with the PRISMA reporting guidelines. Results: We describe 63 studies in which the direct MGIA has been applied across species for the evaluation of TB drugs and novel TB vaccine candidates, the study of clinical cohorts including those with comorbidities, and to further understanding of potential immune correlates of protection from TB. We provide a comprehensive update on progress of the assay since its conception and critically evaluate current findings and evidence supporting its utility, highlighting priorities for future directions. Discussion: While further standardisation and validation work is required, significant advancements have been made in the past two decades. The direct MGIA provides a potentially valuable tool for the early evaluation of TB drug and vaccine candidates, clinical cohorts, and immune mechanisms of mycobacterial control. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023423491.

The lymphatic filariasis treatment study landscape: A systematic review of study characteristics and the case for an individual participant data platform.

BACKGROUND: Lymphatic filariasis (LF) is a neglected tropical disease (NTD) targeted by the World Health Organization for elimination as a public health problem (EPHP). Since 2000, more than 9 billion treatments of antifilarial medicines have been distributed through mass drug administration (MDA) programmes in 72 endemic countries and 17 countries have reached EPHP. Yet in 2021, nearly 900 million people still required MDA with combinations of albendazole, diethylcarbamazine and/or ivermectin. Despite the reliance on these drugs, there remain gaps in understanding of variation in responses to treatment. As demonstrated for other infectious diseases, some urgent questions could be addressed by conducting individual participant data (IPD) meta-analyses. Here, we present the results of a systematic literature review to estimate the abundance of IPD on pre- and post-intervention indicators of infection and/or morbidity and assess the feasibility of building a global data repository. METHODOLOGY: We searched literature published between 1st January 2000 and 5th May 2023 in 15 databases to identify prospective studies assessing LF treatment and/or morbidity management and disease prevention (MMDP) approaches. We considered only studies where individual participants were diagnosed with LF infection or disease and were followed up on at least one occasion after receiving an intervention/treatment. PRINCIPAL FINDINGS: We identified 138 eligible studies from 23 countries, having followed up an estimated 29,842 participants after intervention. We estimate 14,800 (49.6%) IPD on pre- and post-intervention infection indicators including microfilaraemia, circulating filarial antigen and/or ultrasound indicators measured before and after intervention using 8 drugs administered in various combinations. We identified 33 studies on MMDP, estimating 6,102 (20.4%) IPD on pre- and post-intervention clinical morbidity indicators only. A further 8,940 IPD cover a mixture of infection and morbidity outcomes measured with other diagnostics, from participants followed for adverse event outcomes only or recruited after initial intervention. CONCLUSIONS: The LF treatment study landscape is heterogeneous, but the abundance of studies and related IPD suggest that establishing a global data repository to facilitate IPD meta-analyses would be feasible and useful to address unresolved questions on variation in treatment outcomes across geographies, demographics and in underrepresented groups. New studies using more standardized approaches should be initiated to address the scarcity and inconsistency of data on morbidity management.

Characterisation of populations at risk of sub-optimal dosing of artemisinin-based combination therapy in Africa.

Selection of resistant malaria strains occurs when parasites are exposed to inadequate antimalarial drug concentrations. The proportion of uncomplicated falciparum malaria patients at risk of being sub-optimally dosed with the current World Health Organization (WHO) recommended artemisinin-based combination therapies (ACTs) is unknown. This study aims to estimate this proportion and the excess number of treatment failures (recrudescences) associated with sub-optimal dosing in Sub-Saharan Africa. Sub-populations at risk of sub-optimal dosing include wasted children <5 years of age, patients with hyperparasitaemia, pregnant women, people living with HIV, and overweight adults. Country-level data on population structure were extracted from openly accessible data sources. Pooled adjusted Hazard Ratios for PCR-confirmed recrudescence were estimated for each risk group from published meta-analyses using fixed-effect meta-analysis. In 2020, of the estimated 153.1 million uncomplicated P. falciparum malaria patients in Africa, the largest risk groups were the hyperparasitaemic patients (13.2 million, 8.6% of uncomplicated malaria cases) and overweight adults (10.3 million, 6.7% of uncomplicated cases). The estimated excess total number of treatment failures ranged from 0.338 million for a 98% baseline ACT efficacy to 1.352 million for a 92% baseline ACT efficacy. Our study shows that an estimated nearly 1 in 4 people with uncomplicated confirmed P. falciparum malaria in Africa are at risk of receiving a sub-optimal antimalarial drug dosing. This increases the risk of antimalarial drug resistance and poses a serious threat to malaria control and elimination efforts. Changes in antimalarial dosing or treatment duration of current antimalarials may be needed and new antimalarials development should ensure sufficient drug concentration levels in these sub-populations that carry a high malaria burden.

A rapid review of community engagement and informed consent processes for adaptive platform trials and alternative design trials for public health emergencies.

Background : Public Health Emergencies (PHE) demand expeditious research responses to evaluate new or repurposed therapies and prevention strategies. Alternative Design Trials (ADTs) and Adaptive Platform Trials (APTs) have enabled efficient large-scale testing of biomedical interventions during recent PHEs. Design features of these trials may have implications for engagement and/or informed consent processes. We aimed to rapidly review evidence on engagement and informed consent for ADTs and APTs during PHE to consider what (if any) recommendations can inform practice. Method : In 2022, we searched 8 prominent databases for relevant peer reviewed publications and guidelines for ADTs/APTs in PHE contexts. Articles were selected based on pre-identified inclusion and exclusion criteria. We reviewed protocols and informed consent documents for a sample of large platform trials and consulted with key informants from ADTs/APT trial teams. Data were extracted and summarised using narrative synthesis. Results : Of the 49 articles included, 10 were guidance documents, 14 discussed engagement, 10 discussed informed consent, and 15 discussed both. Included articles addressed ADTs delivered during the West African Ebola epidemic and APTs delivered during COVID-19. PHE clinical research guidance documents highlight the value of ADTs/APTs and the importance of community engagement, but do not provide practice-specific guidance for engagement or informed consent. Engagement and consent practice for ADTs conducted during the West African Ebola epidemic have been well-documented. For COVID-19, engagement and consent practice was described for APTs primarily delivered in high income countries with well-developed health service structures. A key consideration is strong communication of the complexity of trial design in clear, accessible ways. Conclusion: We highlight key considerations for best practice in community engagement and informed consent relevant to ADTs and APTs for PHEs which may helpfully be included in future guidance. Protocol: The review protocol is published online at Prospero on 15/06/2022: registration number CRD42022334170.

Scoping review protocol on research prioritisation for preparedness and response to outbreaks of high consequence pathogens.

Background : Prioritisation of research activities for infectious disease pathogens is usually undertaken through the identification of important research and knowledge gaps. Research prioritisation is an essential element of both effective responses to disease outbreaks and adequate preparedness. There is however currently no published mapping of activities on and evidence from research prioritisation for high consequence pathogens. The objectives of this review are to map all published research prioritisation exercises on high-consequence pathogens; provide an overview of methodologies employed for prioritising research for these pathogens; describe monitoring and evaluation processes for research areas prioritised; and identify any standards and guidance for effectively undertaking research prioritisation activities for high consequence pathogens. Methods: The Joanna Briggs Institute guidance of scoping review conduct will be used. The search will be undertaken using the key terms of "research prioritisation", "response", "control", and related terms, and a list of high-consequence pathogens derived from WHO (2020), EMERGE (2019), Europe CDC (2022) and the Association of Southeast Asian Nations (2021). We will search WHO Global Index Medicus; Ovid Medline; Ovid Embase; Ovid Global Health; and Scopus. Backward citations review of the included full text documents will also be conducted. Google Scholar and Overton will be searched for grey literature. Two independent reviewers will screen the retrieved documents using Rayyan and extract data in a data extraction template in Microsoft Excel 2021. Screening results will be presented using the PRISMA-ScR template with narrative synthesis undertaken for the extracted data. Conclusion: This review will map existing research priorities for high consequence pathogens. Further, it will provide an understanding of methodologies used for prioritisation, processes for monitoring and evaluation of progress made against research agendas, and evidence on standards that could be recommended for effective prioritisation of research for high consequence pathogens.

Standard of care for viral haemorrhagic fevers (VHFs): a systematic review of clinical management guidelines for high-priority VHFs.

The Sudan virus disease outbreak in Uganda in 2022 showed our vulnerability to viral haemorrhagic fevers (VHFs). Although there are regular outbreaks of VHFs with high morbidity and mortality, which disproportionally affect low-income settings, our understanding of how to treat them remains inadequate. In this systematic review, we aim to explore the availability, scope, standardisation, and quality of clinical management guidelines for VHFs. We identified 32 guidelines, 25 (78%) of which were low quality and did not have supporting evidence and eight (25%) of which had been produced or updated in the past 3 years. Guidance on supportive care and therapeutics had little detail and was sometimes contradictory. Guidelines based on uncertain evidence are a risk to patients, an ethical challenge for clinicians, and a challenge to implementing trials due to heterogeneous standards of care. We recommend a standard living guideline framework to improve the quality, scope, and applicability of guidelines. Furthermore, investments into trials should aim to identify optimal treatment strategies for VHFs and prioritise affordable and scalable interventions to improve outcomes globally.

Correction: The 20-minute whole blood clotting test (20WBCT) for snakebite coagulopathy-A systematic review and meta-analysis of diagnostic test accuracy.

[This corrects the article DOI: 10.1371/journal.pntd.0009657.].

Correction: A systematic review and an individual patient data meta-analysis of ivermectin use in children weighing less than fifteen kilograms: Is it time to reconsider the current contraindication?

[This corrects the article DOI: 10.1371/journal.pntd.0009144.].

Effect of mindfulness-based programmes on elite athlete mental health: a systematic review and meta-analysis.

OBJECTIVE: To determine the effectiveness of mindfulness-based programmes (MBPs) on the mental health of elite athletes. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Eight online databases (Embase, PsycINFO, SPORTDiscus, MEDLINE, Scopus, Cochrane CENTRAL, ProQuest Dissertations & Theses and Google Scholar), plus forward and backward searching from included studies and previous systematic reviews. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Studies were included if they were randomised controlled trials (RCTs) that compared an MBP against a control, in current or former elite athletes. RESULTS: Of 2386 articles identified, 12 RCTs were included in this systematic review and meta-analysis, comprising a total of 614 elite athletes (314 MBPs and 300 controls). Overall, MBPs improved mental health, with large significant pooled effect sizes for reducing symptoms of anxiety (hedges g=-0.87, number of studies (n)=6, p=0.017, I 2=90) and stress (g=-0.91, n=5, p=0.012, I 2=74) and increasing psychological well-being (g=0.96, n=5, p=0.039., I 2=89). Overall, the risk of bias and certainty of evidence was moderate, and all findings were subject to high estimated levels of heterogeneity. CONCLUSION: MBPs improved several mental health outcomes. Given the moderate degree of evidence, high-quality, adequately powered trials are required in the future. These studies should emphasise intervention fidelity, teacher competence and scalability within elite sport. PROSPERO REGISTRATION NUMBER: CRD42020176654.

Preparing for pandemics: a systematic review of pandemic influenza clinical management guidelines.

BACKGROUND: The COVID-19 pandemic has highlighted the importance of evidence-based clinical decision-making. Clinical management guidelines (CMGs) may help reduce morbidity and mortality by improving the quality of clinical decisions. This systematic review aims to evaluate the availability, inclusivity, and quality of pandemic influenza CMGs, to identify gaps that can be addressed to strengthen pandemic preparedness in this area. METHODS: Ovid Medline, Ovid Embase, TRIP (Turning Research Into Practice), and Guideline Central were searched systematically from January 2008 to 23rd June 2022, complemented by a grey literature search till 16th June 2022. Pandemic influenza CMGs including supportive care or empirical treatment recommendations were included. Two reviewers independently extracted data from the included studies and assessed their quality using AGREE II (Appraisal of Guidelines for Research & Evaluation). The findings are presented narratively. RESULTS: Forty-eight CMGs were included. They were produced in high- (42%, 20/48), upper-middle- (40%, 19/48), and lower-middle (8%, 4/48) income countries, or by international organisations (10%, 5/48). Most CMGs (81%, 39/48) were over 5 years old. Guidelines included treatment recommendations for children (75%, 36/48), pregnant women (54%, 26/48), people with immunosuppression (33%, 16/48), and older adults (29%, 14/48). Many CMGs were of low quality (median overall score: 3 out of 7 (range 1-7). All recommended oseltamivir; recommendations for other neuraminidase inhibitors and supportive care were limited and at times contradictory. Only 56% (27/48) and 27% (13/48) addressed oxygen and fluid therapy, respectively. CONCLUSIONS: Our data highlights the limited availability of up-to-date pandemic influenza CMGs globally. Of those identified, many were limited in scope and quality and several lacked recommendations for specific at-risk populations. Recommendations on supportive care, the mainstay of treatment, were limited and heterogeneous. The most recent guideline highlighted that the evidence-base to support antiviral treatment recommendations is still limited. There is an urgent need for trials into treatment and supportive care strategies including for different risk populations. New evidence should be incorporated into globally accessible guidelines, to benefit patient outcomes. A 'living guideline' framework is recommended and further research into guideline implementation in different resourced settings, particularly low- and middle-income countries.

An evaluation of global Chikungunya clinical management guidelines: A systematic review.

Background: Chikungunya virus (CHIKV) has expanded its geographical reach in recent decades and is an emerging global health threat. CHIKV can cause significant morbidity and lead to chronic, debilitating arthritis/arthralgia in up to 40% of infected individuals. Prevention, early identification, and clinical management are key for improving outcomes. The aim of this review is to evaluate the quality, availability, inclusivity, and scope of evidence-based clinical management guidelines (CMG) for CHIKV globally. Methods: We conducted a systematic review. Six databases were searched from Jan 1, 1989, to 14 Oct 2021 and grey literature until Sept 16, 2021, for CHIKV guidelines providing supportive care and treatment recommendations. Quality was assessed using the appraisal of Guidelines for Research and Evaluation tool. Findings are presented in a narrative synthesis. PROSPERO registration: CRD42020167361. Findings: 28 CMGs were included; 54% (15/28) were produced more than 5 years ago, and most were of low-quality (median score 2 out of 7 (range 1-7)). There were variations in the CMGs' guidance on the management of different at-risk populations, long-term sequelae, and the prevention of disease transmission. While 54% (15/28) of CMGs recommended hospitalisation for severe cases, only 39% (11/28) provided guidance for severe disease management. Further, 46% (13/28) advocated for steroids in the chronic phase, but 18% (5/28) advised against its use. Interpretation: There was a lack of high-quality CMGs that provided supportive care and treatment guidance, which may impact patient care and outcomes. It is essential that existing guidelines are updated and adapted to provide detailed evidence-based treatment guidelines for different at-risk populations. This study also highlights a need for more research into the management of the acute and chronic phases of CHIKV infection to inform evidence-based care. Funding: The UK Foreign, Commonwealth and Development Office, Wellcome Trust [215091/Z/18/Z] and the Bill & Melinda Gates Foundation [OPP1209135].

Availability, scope and quality of monkeypox clinical management guidelines globally: a systematic review.

BACKGROUND: Monkeypox (MPX) is an important human Orthopoxvirus infection. There has been an increase in MPX cases and outbreaks in endemic and non-endemic regions in recent decades. We appraised the availability, scope, quality and inclusivity of clinical management guidelines for MPX globally. METHODS: For this systematic review, we searched six databases from inception until 14 October 2021, augmented by a grey literature search until 17 May 2022. MPX guidelines providing treatment and supportive care recommendations were included, with no exclusions for language. Two reviewers assessed the guidelines. Quality was assessed using the Appraisal of Guidelines for Research and Evaluation II tool. RESULTS: Of 2026 records screened, 14 guidelines were included. Overall, most guidelines were of low-quality with a median score of 2 out of 7 (range: 1-7), lacked detail and covered a narrow range of topics. Most guidelines focused on adults, five (36%) provided some advice for children, three (21%) for pregnant women and three (21%) for people living with HIV. Treatment guidance was mostly limited to advice on antivirals; seven guidelines advised cidofovir (four specified for severe MPX only); 29% (4/14) tecovirimat, and 7% (1/14) brincidofovir. Only one guideline provided recommendations on supportive care and treatment of complications. All guidelines recommended vaccination as post-exposure prophylaxis (PEP). Three guidelines advised on vaccinia immune globulin as PEP for severe cases in people with immunosuppression. CONCLUSION: Our results highlight a lack of evidence-based clinical management guidelines for MPX globally. There is a clear and urgent need for research into treatment and prophylaxis including for different risk populations. The current outbreak provides an opportunity to accelerate this research through coordinated high-quality studies. New evidence should be incorporated into globally accessible guidelines, to benefit patient and epidemic outcomes. A 'living guideline' framework is recommended. PROSPERO REGISTRATION NUMBER: CRD42020167361.

Systematic review of host genomic biomarkers of invasive bacterial disease: Distinguishing bacterial from non-bacterial causes of acute febrile illness.

BACKGROUND: Infectious diseases play a significant role in the global burden of disease. The gold standard for the diagnosis of bacterial infection, bacterial culture, can lead to diagnostic delays and inappropriate antibiotic use. The advent of high- throughput technologies has led to the discovery of host-based genomic biomarkers of infection, capable of differentiating bacterial from other causes of infection, but few have achieved validation for use in a clinical setting. METHODS: A systematic review was performed. PubMed/Ovid Medline, Ovid Embase and Scopus databases were searched for relevant studies from inception up to 30/03/2022 with forward and backward citation searching of key references. Studies assessing the diagnostic performance of human host genomic biomarkers of bacterial infection were included. Study selection and assessment of quality were conducted by two independent reviewers. A meta-analysis was undertaken using a diagnostic random-effects model. The review was registered with PROSPERO (ID: CRD42021208462). FINDINGS: Seventy-two studies evaluating the performance of 116 biomarkers in 16,216 patients were included. Forty-six studies examined TB-specific biomarker performance and twenty-four studies assessed biomarker performance in a paediatric population. The results of pooled sensitivity, specificity, negative and positive likelihood ratio, and diagnostic odds ratio of genomic biomarkers of bacterial infection were 0.80 (95% CI 0.78 to 0.82), 0.86 (95% CI 0.84 to 0.88), 0.18 (95% CI 0.16 to 0.21), 5.5 (95% CI 4.9 to 6.3), 30.1 (95% CI 24 to 37), respectively. Significant between-study heterogeneity (I2 77%) was present. INTERPRETATION: Host derived genomic biomarkers show significant potential for clinical use as diagnostic tests of bacterial infection however, further validation and attention to test platform is warranted before clinical implementation can be achieved. FUNDING: No funding received.

The Prevalence of Psychiatric Disorders in General Hospital Inpatients: A Systematic Umbrella Review.

BACKGROUND: To inform the future development of consultation-liaison psychiatry services, we need accurate information on the prevalence of psychiatric disorders in the general hospital inpatient setting. Systematic reviews have summarized the literature on specific aspects of this broad topic, but there has been no high-level overview that aggregates their findings and identifies gaps in the relevant literature. OBJECTIVE: We aimed to produce a comprehensive overview of the field, summarizing the research literature on the prevalence of psychiatric disorders (i.e., interview-based psychiatric diagnoses) in general hospital inpatients. We did this using a systematic umbrella review (systematic review of systematic reviews), which is the best and most efficient method for summarizing a broad area of research. METHODS: We searched Ovid Medline, Ovid Embase, Ovid PsycINFO, EBSCO CINAHL, and Scopus from database inception to September 2021 for systematic reviews that provided a pooled prevalence estimate, or prevalence range, for interview-diagnosed psychiatric disorders in general hospital inpatients. Two reviewers independently assessed articles and extracted data. The review is registered with PROSPERO, number CRD42019125574. RESULTS: We screened 11,728 articles and included 10 systematic reviews in our umbrella review. We were able to extract pooled prevalence estimates from these as follows: major depression 12% to 20%, any anxiety disorder 8%, generalized anxiety disorder 5%, panic disorder 3%, delirium 15%. We were only able to extract a prevalence range for dementia, which was 3% to 63%. We found no systematic reviews from which we could extract prevalence data for the other psychiatric disorders that we included in our searches, indicating important gaps. From these data, we estimated that approximately one-third of inpatients have a psychiatric disorder. CONCLUSIONS: Psychiatric disorders are very common in general hospital inpatients. While the planning of consultation-liaison psychiatry services will benefit from more research on the prevalence of each of the full range of disorders encountered in the inpatient setting, our findings indicate that we already know enough to justify increased and more population-based service provision.