Fitting a square peg into a round hole: are the current Surviving Sepsis Campaign guidelines feasible for Africa?

In their article, Baelani and colleagues surveyed anesthesia providers from African low- and middle-income countries (LMICs) to evaluate whether or not the current Surviving Sepsis Campaign (SSC) guidelines are feasible in such resource-constrained settings. The authors report that an alarmingly low percentage of hospitals have the capacity to implement the SSC guidelines in their entirety but a higher percentage are able to implement the majority of SSC guidelines and grade 1 recommendations. In reality, the probability of adherence to SSC guidelines for septic management is even lower than reported, given that the majority of sepsis management in African LMICs is likely performed by non-intensivists outside of intensive care units. Efforts to address the challenges of managing severely ill patients in LMICs have recently been taken on by the World Health Organization. After reviewing available evidence for sepsis management predominantly from high-income countries, a panel of experts developed a consensus-based strategy tailored for resource-limited settings. However, more research that can evaluate the challenges specific to sepsis management in LMICs and not currently addressed by the SSC guidelines is needed. Comprehensive, evidence-based guidelines combined with innovative approaches to sepsis management in LMICs are required to make a meaningful impact on worldwide sepsis survival

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

This work was supported by the UK Foreign, Commonwealth and Development Office and Wellcome (215091/Z/18/Z) and the Bill & Melinda Gates Foundation (OPP1209135). The GloPID-R Secretariat is a project that receives funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 874667. SL is an MRC Clinical Research Training fellow (MR/T001151/1).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.Publisher PDFPeer reviewe

An evaluation of global Chikungunya clinical management guidelines : a systematic review

This work was supported by funding from the UK Foreign, Commonwealth and Development Office, Wellcome Trust [215091/Z/18/Z] and the Bill & Melinda Gates Foundation [OPP1209135]. Thanks to the ISARIC Global Support Centre for their invaluable logistical and administrative support on this project.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].Publisher PDFPeer reviewe

Clinical Presentation of Patients with Ebola Virus Disease in Conakry, Guinea

BACKGROUND: In March 2014, the World Health Organization was notified of an outbreak of Zaire ebolavirus in a remote area of Guinea. The outbreak then spread to the capital, Conakry, and to neighboring countries and has subsequently become the largest epidemic of Ebola virus disease (EVD) to date. METHODS: From March 25 to April 26, 2014, we performed a study of all patients with laboratory-confirmed EVD in Conakry. Mortality was the primary outcome. Secondary outcomes included patient characteristics, complications, treatments, and comparisons between survivors and nonsurvivors. RESULTS: Of 80 patients who presented with symptoms, 37 had laboratory-confirmed EVD. Among confirmed cases, the median age was 38 years (interquartile range, 28 to 46), 24 patients (65%) were men, and 14 (38%) were health care workers; among the health care workers, nosocomial transmission was implicated in 12 patients (32%). Patients with confirmed EVD presented to the hospital a median of 5 days (interquartile range, 3 to 7) after the onset of symptoms, most commonly with fever (in 84% of the patients; mean temperature, 38.6°C), fatigue (in 65%), diarrhea (in 62%), and tachycardia (mean heart rate, \u3e93 beats per minute). Of these patients, 28 (76%) were treated with intravenous fluids and 37 (100%) with antibiotics. Sixteen patients (43%) died, with a median time from symptom onset to death of 8 days (interquartile range, 7 to 11). Patients who were 40 years of age or older, as compared with those under the age of 40 years, had a relative risk of death of 3.49 (95% confidence interval, 1.42 to 8.59; P=0.007). CONCLUSIONS: Patients with EVD presented with evidence of dehydration associated with vomiting and severe diarrhea. Despite attempts at volume repletion, antimicrobial therapy, and limited laboratory services, the rate of death was 43%

Being Ready to Treat Ebola Virus Disease Patients

As the outbreak of Ebola virus disease (EVD) in West Africa continues, clinical preparedness is needed in countries at risk for EVD (e.g., United States) and more fully equipped and supported clinical teams in those countries with epidemic spread of EVD in Africa. Clinical staff must approach the patient with a very deliberate focus on providing effective care while assuring personal safety. To do this, both individual health care providers and health systems must improve EVD care. Although formal guidance toward these goals exists from the World Health Organization, Medecin Sans Frontières, the Centers for Disease Control and Prevention, and other groups, some of the most critical lessons come from personal experience. In this narrative, clinicians deployed by the World Health Organization into a wide range of clinical settings in West Africa distill key, practical considerations for working safely and effectively with patients with EVD

Mycobacterium tuberculosis bloodstream infection prevalence, diagnosis, and mortality risk in seriously ill adults with HIV: a systematic review and meta-analysis of individual patient data.

BACKGROUND: The clinical and epidemiological significance of HIV-associated Mycobacterium tuberculosis bloodstream infection (BSI) is incompletely understood. We hypothesised that M tuberculosis BSI prevalence has been underestimated, that it independently predicts death, and that sputum Xpert MTB/RIF has suboptimal diagnostic yield for M tuberculosis BSI. METHODS: We did a systematic review and individual patient data (IPD) meta-analysis of studies performing routine mycobacterial blood culture in a prospectively defined patient population of people with HIV aged 13 years or older. Studies were identified through searching PubMed and Scopus up to Nov 10, 2018, without language or date restrictions and through manual review of reference lists. Risk of bias in the included studies was assessed with an adapted QUADAS-2 framework. IPD were requested for all identified studies and subject to harmonised inclusion criteria: age 13 years or older, HIV positivity, available CD4 cell count, a valid mycobacterial blood culture result (excluding patients with missing data from lost or contaminated blood cultures), and meeting WHO definitions for suspected tuberculosis (presence of screening symptom). Predicted probabilities of M tuberculosis BSI from mixed-effects modelling were used to estimate prevalence. Estimates of diagnostic yield of sputum testing with Xpert (or culture if Xpert was unavailable) and of urine lipoarabinomannan (LAM) testing for M tuberculosis BSI were obtained by two-level random-effect meta-analysis. Estimates of mortality associated with M tuberculosis BSI were obtained by mixed-effect Cox proportional-hazard modelling and of effect of treatment delay on mortality by propensity-score analysis. This study is registered with PROSPERO, number 42016050022. FINDINGS: We identified 23 datasets for inclusion (20 published and three unpublished at time of search) and obtained IPD from 20, representing 96·2% of eligible IPD. Risk of bias for the included studies was assessed to be generally low except for on the patient selection domain, which was moderate in most studies. 5751 patients met harmonised IPD-level inclusion criteria. Technical factors such as number of blood cultures done, timing of blood cultures relative to blood sampling, and patient factors such as inpatient setting and CD4 cell count, explained significant heterogeneity between primary studies. The predicted probability of M tuberculosis BSI in hospital inpatients with HIV-associated tuberculosis, WHO danger signs, and a CD4 count of 76 cells per μL (the median for the cohort) was 45% (95% CI 38-52). The diagnostic yield of sputum in patients with M tuberculosis BSI was 77% (95% CI 63-87), increasing to 89% (80-94) when combined with urine LAM testing. Presence of M tuberculosis BSI compared with its absence in patients with HIV-associated tuberculosis increased risk of death before 30 days (adjusted hazard ratio 2·48, 95% CI 2·05-3·08) but not after 30 days (1·25, 0·84-2·49). In a propensity-score matched cohort of participants with HIV-associated tuberculosis (n=630), mortality increased in patients with M tuberculosis BSI who had a delay in anti-tuberculosis treatment of longer than 4 days compared with those who had no delay (odds ratio 3·15, 95% CI 1·16-8·84). INTERPRETATION: In critically ill adults with HIV-tuberculosis, M tuberculosis BSI is a frequent manifestation of tuberculosis and predicts mortality within 30 days. Improved diagnostic yield in patients with M tuberculosis BSI could be achieved through combined use of sputum Xpert and urine LAM. Anti-tuberculosis treatment delay might increase the risk of mortality in these patients. FUNDING: This study was supported by Wellcome fellowships 109105Z/15/A and 105165/Z/14/A