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BACKGROUND: The aim of this study was to characterize the epidemiology of human seasonal coronaviruses (HCoVs) in southern Malawi. METHODS: We tested for HCoVs 229E, OC43, NL63, and HKU1 using real-time polymerase chain reaction (PCR) on upper respiratory specimens from asymptomatic controls and individuals of all ages recruited through severe acute respiratory illness (SARI) surveillance at Queen Elizabeth Central Hospital, Blantyre, and a prospective influenza-like illness (ILI) observational study between 2011 and 2017. We modeled the probability of having a positive PCR for each HCoV using negative binomial models, and calculated pathogen-attributable fractions (PAFs). RESULTS: Overall, 8.8% (539/6107) of specimens were positive for ≥1 HCoV. OC43 was the most frequently detected HCoV (3.1% [191/6107]). NL63 was more frequently detected in ILI patients (adjusted incidence rate ratio [aIRR], 9.60 [95% confidence interval {CI}, 3.25-28.30]), while 229E (aIRR, 8.99 [95% CI, 1.81-44.70]) was more frequent in SARI patients than asymptomatic controls. In adults, 229E and OC43 were associated with SARI (PAF, 86.5% and 89.4%, respectively), while NL63 was associated with ILI (PAF, 85.1%). The prevalence of HCoVs was similar between children with SARI and controls. All HCoVs had bimodal peaks but distinct seasonality. CONCLUSIONS: OC43 was the most prevalent HCoV in acute respiratory illness of all ages. Individual HCoVs had distinct seasonality that differed from temperate settings.
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Infecciones por Coronavirus , Coronavirus , Estaciones del Año , Humanos , Malaui/epidemiología , Masculino , Adulto , Preescolar , Femenino , Niño , Adolescente , Lactante , Persona de Mediana Edad , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/virología , Adulto Joven , Coronavirus/genética , Coronavirus/aislamiento & purificación , Estudios Prospectivos , Infecciones del Sistema Respiratorio/epidemiología , Infecciones del Sistema Respiratorio/virología , Anciano , Recién NacidoRESUMEN
Context: Agronomic data such as applied inputs, management practices, and crop yields are needed for assessing productivity, nutrient balances, resource use efficiency, as well as other aspects of environmental and economic performance of cropping systems. In many instances, however, these data are only available at a coarse level of aggregation or simply do not exist. Objectives: Here we developed an approach that identifies sites for agronomic data collection for a given crop and country, seeking a balance between minimizing data collection efforts and proper representation of the main crop producing areas. Methods: The developed approach followed a stratified sampling method based on a spatial framework that delineates major climate zones and crop area distribution maps, which guides selection of sampling areas (SA) until half of the national harvested area is covered. We provided proof of concept about the robustness of the approach using three rich databases including data on fertilizer application rates for maize, wheat, and soybean in Argentina, soybean in the USA, and maize in Kenya, which were collected via local experts (Argentina) and field surveys (USA and Kenya). For validation purposes, fertilizer rates per crop and nutrient derived at (sub-) national level following our approach were compared against those derived using all data collected from the whole country. Results: Application of the approach in Argentina, USA, and Kenya resulted in selection of 12, 28, and 10 SAs, respectively. For each SA, three experts or 20 fields were sufficient to give a robust estimate of average fertilizer rates applied by farmers. Average rates at national level derived from our approach compared well with those derived using the whole database ( ± 10 kg N, ± 2 kg P, ± 1 kg S, and ± 5 kg K per ha) requiring less than one third of the observations. Conclusions: The developed minimum crop data collection approach can fill the agronomic data gaps in a cost-effective way for major crop systems both in large- and small-scale systems. Significance: The proposed approach is generic enough to be applied to any crop-country combination to guide collection of key agricultural data at national and subnational levels with modest investment especially for countries that do not currently collect data.
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BACKGROUND: Immunocompromised patients may be at higher risk of mortality if hospitalised with Coronavirus Disease 2019 (COVID-19) compared with immunocompetent patients. However, previous studies have been contradictory. We aimed to determine whether immunocompromised patients were at greater risk of in-hospital death and how this risk changed over the pandemic. METHODS AND FINDINGS: We included patients > = 19 years with symptomatic community-acquired COVID-19 recruited to the ISARIC WHO Clinical Characterisation Protocol UK prospective cohort study. We defined immunocompromise as immunosuppressant medication preadmission, cancer treatment, organ transplant, HIV, or congenital immunodeficiency. We used logistic regression to compare the risk of death in both groups, adjusting for age, sex, deprivation, ethnicity, vaccination, and comorbidities. We used Bayesian logistic regression to explore mortality over time. Between 17 January 2020 and 28 February 2022, we recruited 156,552 eligible patients, of whom 21,954 (14%) were immunocompromised. In total, 29% (n = 6,499) of immunocompromised and 21% (n = 28,608) of immunocompetent patients died in hospital. The odds of in-hospital mortality were elevated for immunocompromised patients (adjusted OR 1.44, 95% CI [1.39, 1.50], p < 0.001). Not all immunocompromising conditions had the same risk, for example, patients on active cancer treatment were less likely to have their care escalated to intensive care (adjusted OR 0.77, 95% CI [0.7, 0.85], p < 0.001) or ventilation (adjusted OR 0.65, 95% CI [0.56, 0.76], p < 0.001). However, cancer patients were more likely to die (adjusted OR 2.0, 95% CI [1.87, 2.15], p < 0.001). Analyses were adjusted for age, sex, socioeconomic deprivation, comorbidities, and vaccination status. As the pandemic progressed, in-hospital mortality reduced more slowly for immunocompromised patients than for immunocompetent patients. This was particularly evident with increasing age: the probability of the reduction in hospital mortality being less for immunocompromised patients aged 50 to 69 years was 88% for men and 83% for women, and for those >80 years was 99% for men and 98% for women. The study is limited by a lack of detailed drug data prior to admission, including steroid doses, meaning that we may have incorrectly categorised some immunocompromised patients as immunocompetent. CONCLUSIONS: Immunocompromised patients remain at elevated risk of death from COVID-19. Targeted measures such as additional vaccine doses, monoclonal antibodies, and nonpharmaceutical preventive interventions should be continually encouraged for this patient group. TRIAL REGISTRATION: ISRCTN 66726260.
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COVID-19 , Masculino , Humanos , Femenino , Persona de Mediana Edad , Anciano , SARS-CoV-2 , Estudios Prospectivos , Mortalidad Hospitalaria , Teorema de Bayes , Huésped Inmunocomprometido , Reino Unido/epidemiología , Organización Mundial de la SaludRESUMEN
PURPOSE OF THE REVIEW: To describe important recent developments in the treatment of multidrug resistant tuberculosis (MDR-TB). RECENT FINDINGS: In the last decade, novel and repurposed antituberculosis drugs have transformed MDR-TB treatment with improved rates of treatment success, better tolerability and safety and reduced duration. As recently as 2016, standard care relied on up to seven drugs for 24âmonths with treatment success no better than 70%. Seven drug shorter so-called "Bangladesh" style regimens subsequently achieved similar or better results at a duration of 9-12âmonths but concerns about first-line resistance additional to rifampicin hampered global uptake. After conditional approval in 2012, the novel agent bedaquiline was demonstrated to improve outcomes and reduce mortality when used in longer and shorter regimens, resulting in the replacement of injectable agents. In the last 2 years, clinical trials of all-oral 6-month three or four drug regimens containing bedaquiline, pretomanid and linezolid have shown superior efficacy against both longer and shorter traditional regimens, resulting in major changes in WHO guidance. SUMMARY: Although some concerns around safety and emergent bedaquiline resistance remain to be fully addressed, 6-month all oral regimens promise to transform the treatment of people with MDR-TB worldwide.
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Nitroimidazoles , Tuberculosis Resistente a Múltiples Medicamentos , Humanos , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Antituberculosos/uso terapéutico , Quimioterapia Combinada , Resultado del TratamientoRESUMEN
Rationale: Pneumococcal colonization is key to the pathogenesis of invasive disease but is also immunogenic in young adults, protecting against recolonization. Colonization is rarely detected in older adults, despite high rates of pneumococcal disease.Objectives: To establish experimental human pneumococcal colonization in healthy adults aged 50-84 years, to measure the immune response to pneumococcal challenge, and to assess the protective effect of prior colonization against autologous strain rechallenge.Methods: Sixty-four participants were inoculated with Streptococcus pneumoniae (serotype 6B; 80,000 cfu in each nostril). Colonization was determined by bacterial culture of nasal wash, and humoral immune responses were assessed by anticapsular and antiprotein IgG concentrations.Measurements and Main Results: Experimental colonization was established in 39% of participants (25/64) with no adverse events. Colonization occurred in 47% (9/19) of participants aged 50-59 compared with 21% (3/14) in those aged ≥70 years. Previous pneumococcal polysaccharide vaccination did not protect against colonization. Colonization did not confer serotype-specific immune boosting, with a geometric mean titer (95% confidence interval) of 2.7 µg/ml (1.9-3.8) before the challenge versus 3.0 (1.9-4.7) 4 weeks after colonization (P = 0.53). Furthermore, pneumococcal challenge without colonization led to a drop in specific antibody concentrations from 2.8 µg/ml (2.0-3.9) to 2.2 µg/ml (1.6-3.0) after the challenge (P = 0.006). Antiprotein antibody concentrations increased after successful colonization. Rechallenge with the same strain after a median of 8.5 months (interquartile range, 6.7-10.1) led to recolonization in 5/16 (31%).Conclusions: In older adults, experimental pneumococcal colonization is feasible and safe but demonstrates different immunological outcomes compared with younger adults in previous studies.
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Anticuerpos Antibacterianos/inmunología , Portador Sano/inmunología , Infecciones Neumocócicas/inmunología , Streptococcus pneumoniae/inmunología , Factores de Edad , Anciano , Anciano de 80 o más Años , Infecciones Asintomáticas , Técnicas de Cultivo , Estudios de Factibilidad , Femenino , Humanos , Inmunidad Humoral/inmunología , Inmunoglobulina G/inmunología , Masculino , Persona de Mediana Edad , Cavidad Nasal , Líquido del Lavado Nasal , Infecciones Neumocócicas/prevención & control , Vacunas Neumococicas/uso terapéuticoRESUMEN
BACKGROUND: Mechanical ventilation is used to treat respiratory failure in coronavirus disease 2019 (COVID-19). PURPOSE: To review multiple streams of evidence regarding the benefits and harms of ventilation techniques for coronavirus infections, including that causing COVID-19. DATA SOURCES: 21 standard, World Health Organization-specific and COVID-19-specific databases, without language restrictions, until 1 May 2020. STUDY SELECTION: Studies of any design and language comparing different oxygenation approaches in patients with coronavirus infections, including severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS), or with hypoxemic respiratory failure. Animal, mechanistic, laboratory, and preclinical evidence was gathered regarding aerosol dispersion of coronavirus. Studies evaluating risk for virus transmission to health care workers from aerosol-generating procedures (AGPs) were included. DATA EXTRACTION: Independent and duplicate screening, data abstraction, and risk-of-bias assessment (GRADE for certainty of evidence and AMSTAR 2 for included systematic reviews). DATA SYNTHESIS: 123 studies were eligible (45 on COVID-19, 70 on SARS, 8 on MERS), but only 5 studies (1 on COVID-19, 3 on SARS, 1 on MERS) adjusted for important confounders. A study in hospitalized patients with COVID-19 reported slightly higher mortality with noninvasive ventilation (NIV) than with invasive mechanical ventilation (IMV), but 2 opposing studies, 1 in patients with MERS and 1 in patients with SARS, suggest a reduction in mortality with NIV (very-low-certainty evidence). Two studies in patients with SARS report a reduction in mortality with NIV compared with no mechanical ventilation (low-certainty evidence). Two systematic reviews suggest a large reduction in mortality with NIV compared with conventional oxygen therapy. Other included studies suggest increased odds of transmission from AGPs. LIMITATION: Direct studies in COVID-19 are limited and poorly reported. CONCLUSION: Indirect and low-certainty evidence suggests that use of NIV, similar to IMV, probably reduces mortality but may increase the risk for transmission of COVID-19 to health care workers. PRIMARY FUNDING SOURCE: World Health Organization. (PROSPERO: CRD42020178187).
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Infecciones por Coronavirus , Neumonía Viral , Respiración Artificial , Animales , Humanos , Aerosoles , Betacoronavirus , Infecciones por Coronavirus/mortalidad , Infecciones por Coronavirus/transmisión , COVID-19 , Pandemias , Neumonía Viral/mortalidad , Neumonía Viral/transmisión , Ensayos Clínicos Controlados Aleatorios como Asunto , Respiración Artificial/efectos adversos , Respiración Artificial/métodos , SARS-CoV-2 , Síndrome Respiratorio Agudo Grave/transmisión , Organización Mundial de la SaludRESUMEN
BACKGROUND: Sepsis guidelines are widely used in high-income countries and intravenous fluids are an important supportive treatment modality. However, fluids have been harmful in intervention trials in low-income countries, most notably in sub-Saharan Africa. We assessed the relevance, quality and applicability of available guidelines for the fluid management of adult patients with sepsis in this region. METHODS: We identified sepsis guidelines by systematic review with broad search terms, duplicate screening and data extraction. We included peer-reviewed publications with explicit relevance to sepsis and fluid therapy. We excluded those designed exclusively for specific aetiologies of sepsis, for limited geographic locations, or for non-adult populations. We used the AGREE II tool to assess the quality of guideline development, performed a narrative synthesis and used theoretical case scenarios to assess practical applicability to everyday clinical practice in resource-constrained settings. RESULTS: Published sepsis guidelines are heterogeneous in sepsis definition and in quality: 8/10 guidelines had significant deficits in applicability, particularly with reference to resource considerations in low-income settings. Indications for intravenous fluid were hypotension (8/10), clinical markers of hypoperfusion (6/10) and lactataemia (3/10). Crystalloids were overwhelmingly recommended (9/10). Suggested volumes varied; 5/10 explicitly recommended "fluid challenges" with reassessment, totalling between 1 L and 4 L during initial resuscitation. Fluid balance, including later de-escalation of therapy, was not specifically described in any. Norepinephrine was the preferred initial vasopressor (5/10), specifically targeted to MAP > 65 mmHg (3/10), with higher values suggested in pre-existing hypertension (1/10). Recommendations for guidelines were almost universally derived from evidence in high-income countries. None of the guidelines suggested any refinement for patients with malnutrition. CONCLUSIONS: Widely used international guidelines contain disparate recommendations on intravenous fluid use, lack specificity and are largely unattainable in low-income countries given available resources. A relative lack of high-quality evidence from sub-Saharan Africa increases reliance on recommendations which may not be relevant or implementable.
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Fluidoterapia/normas , Guías como Asunto/normas , Sepsis/terapia , África del Sur del Sahara , Fluidoterapia/métodos , Humanos , Calidad de la Atención de Salud/normasRESUMEN
Rationale: In the context of rapid antiretroviral therapy rollout and an increasing burden of noncommunicable diseases, there are few contemporary data describing the etiology and outcome of community-acquired pneumonia (CAP) in sub-Saharan Africa.Objectives: To describe the current etiology of CAP in Malawi and identify risk factors for mortality.Methods: We conducted a prospective observational study of adults hospitalized with CAP to a teaching hospital in Blantyre, Malawi. Etiology was defined by blood culture, Streptococcus pneumoniae urinary antigen detection, sputum mycobacterial culture and Xpert MTB/RIF, and nasopharyngeal aspirate multiplex PCR.Measurements and Main Results: In 459 patients (285 [62.1%] males; median age, 34.7 [interquartile range, 29.4-41.9] yr), 30-day mortality was 14.6% (64/439) and associated with male sex (adjusted odds ratio, 2.60 [95% confidence interval, 1.17-5.78]), symptom duration greater than 7 days (2.78 [1.40-5.54]), tachycardia (2.99 [1.48-6.06]), hypoxemia (4.40 [2.03-9.51]), and inability to stand (3.59 [1.72-7.50]). HIV was common (355/453; 78.4%), frequently newly diagnosed (124/355; 34.9%), but not associated with mortality. S. pneumoniae (98/458; 21.4%) and Mycobacterium tuberculosis (75/326; 23.0%) were the most frequently identified pathogens. Viral infection occurred in 32.6% (148/454) with influenza (40/454; 8.8%) most common. Bacterial-viral coinfection occurred in 9.1% (28/307). Detection of M. tuberculosis was associated with mortality (adjusted odds ratio, 2.44 [1.19-5.01]).Conclusions: In the antiretroviral therapy era, CAP in Malawi remains predominantly HIV associated, with a large proportion attributable to potentially vaccine-preventable pathogens. Strategies to increase early detection and treatment of tuberculosis and improve supportive care, in particular the correction of hypoxemia, should be evaluated in clinical trials to address CAP-associated mortality.
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Infecciones Comunitarias Adquiridas/microbiología , Infecciones Comunitarias Adquiridas/mortalidad , Neumonía/microbiología , Neumonía/mortalidad , Adulto , Estudios de Cohortes , Infecciones Comunitarias Adquiridas/terapia , Femenino , Hospitalización , Humanos , Malaui , Masculino , Neumonía/terapia , Factores de Riesgo , Tasa de SupervivenciaRESUMEN
Background: The impact of human immunodeficiency virus (HIV) infection on influenza incidence and severity in adults in sub-Saharan Africa is unclear. Seasonal influenza vaccination is recommended for HIV-infected persons in developed settings but is rarely implemented in Africa. Methods: We conducted a prospective cohort study to compare the incidence of laboratory-confirmed influenza illness between HIV-infected and HIV-uninfected adults in Blantyre, Malawi. In a parallel case-control study, we explored risk factors for severe influenza presentation of severe (hospitalized) lower respiratory tract infection, and mild influenza (influenza-like illness [ILI]). Results: The cohort study enrolled 608 adults, of whom 360 (59%) were HIV infected. Between April 2013 and March 2015, 24 of 229 ILI episodes (10.5%) in HIV-infected and 5 of 119 (4.2%) in HIV-uninfected adults were positive for influenza by means of polymerase chain reaction (incidence rate, 46.0 vs 14.5 per 1000 person-years; incidence rate ratio, 2.75; 95% confidence interval, 1.02-7.44; P = .03; adjusted for age, sex, household crowding, and food security). In the case-control study, influenza was identified in 56 of 518 patients (10.8%) with hospitalized lower respiratory tract infection, and 88 or 642 (13.7%) with ILI. The HIV prevalence was 69.6% and 29.6%, respectively, among influenza-positive case patients and controls. HIV was a significant risk factor for severe influenza (odds ratio, 4.98; 95% confidence interval, 2.09-11.88; P < .001; population-attributable fraction, 57%; adjusted for season, sanitation facility, and food security). Conclusions: HIV is an important risk factor for influenza-associated ILI and severe presentation in this high-HIV prevalence African setting. Targeted influenza vaccination of HIV-infected African adults should be reevaluated, and the optimal mechanism for vaccine introduction in overstretched health systems needs to be determined.
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Costo de Enfermedad , Infecciones por VIH/complicaciones , Gripe Humana/epidemiología , Índice de Severidad de la Enfermedad , Adulto , Estudios de Casos y Controles , Femenino , VIH/aislamiento & purificación , Infecciones por VIH/epidemiología , Hospitalización/estadística & datos numéricos , Humanos , Incidencia , Malaui/epidemiología , Masculino , Persona de Mediana Edad , Orthomyxoviridae/genética , Orthomyxoviridae/aislamiento & purificación , Prevalencia , Estudios Prospectivos , Factores de Riesgo , Estaciones del AñoRESUMEN
Community-acquired pneumonia (CAP) is a common cause of morbidity and mortality in adults worldwide, but its epidemiology varies markedly by region. Whilst in high-income countries, the predominant burden of CAP is in the elderly and those with chronic cardiovascular and pulmonary co-morbidity, CAP patients in low-income settings are often of working age and, in sub-Saharan Africa, frequently HIV-positive. Although region-specific aetiological data are limited, they are sufficient to highlight major trends: in high-burden settings, tuberculosis (TB) is a common cause of acute CAP; Gram-negative pathogens such as Klebsiella pneumoniae are regionally important; and HIV-associated opportunistic infections are common but difficult to diagnose. These differences in epidemiology and aetiological profile suggest that modified approaches to diagnosis, severity assessment and empirical antimicrobial therapy of CAP are necessary, but tailored individualized management approaches are constrained by limitations in the availability of radiological and laboratory diagnostic services, as well as medical expertise. The widespread introduction of the Xpert MTB/RIF platform represents a major advance for TB diagnosis, but innovations in rapid diagnostics for other opportunistic pathogens are urgently needed. Severity assessment tools (e.g. CURB65) that are used to guide early management decisions in CAP have not been widely validated in low-income settings and locally adapted tools are required. The optimal approach to initial antimicrobial therapy choices such as the need to provide early empirical cover for atypical bacteria and TB remain poorly defined. Improvements in supportive care such as correcting hypoxaemia and intravenous fluid management represent opportunities for substantial reductions in mortality.
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Infecciones Comunitarias Adquiridas/etiología , Infecciones Comunitarias Adquiridas/terapia , Países en Desarrollo , Neumonía/etiología , Neumonía/terapia , Adulto , Antiinfecciosos/uso terapéutico , Infecciones Comunitarias Adquiridas/diagnóstico , Humanos , Neumonía/diagnósticoRESUMEN
Community-acquired pneumonia (CAP) in sub-Saharan Africa is a common cause of adult hospitalization and is associated with significant mortality. Human immunodeficiency virus (HIV) prevalence in the region leads to differences in CAP epidemiology compared with most high-income settings: patients are younger, and coinfection with tuberculosis and opportunistic infections is common and difficult to diagnose. Resource limitations affect the availability of medical expertise as well as radiological and laboratory diagnostic services. These factors impact on key aspects of health care, including pathways of investigation, severity assessment, and the selection of empirical antimicrobial therapy. This review summarizes recent data from sub-Saharan Africa describing the burden, etiology, risk factors, and outcome of CAP. We describe the rational and context-appropriate approach to CAP diagnosis and management, including supportive therapy. Priorities for future research to inform strategies for CAP prevention and initial management are suggested.
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Neumonía/epidemiología , África del Sur del Sahara/epidemiología , Infecciones Comunitarias Adquiridas/diagnóstico , Infecciones Comunitarias Adquiridas/epidemiología , Infecciones por VIH/epidemiología , Humanos , Infecciones Oportunistas/epidemiología , Neumonía/diagnóstico , Prevalencia , Tuberculosis Pulmonar/epidemiologíaRESUMEN
Health-care systems, food supply chains, and society in general are threatened by the inexorable rise of antimicrobial resistance. This threat is driven by many factors, one of which is inappropriate antimicrobial treatment. The ability of policy makers and leaders in health care, public health, regulatory agencies, and research and development to deliver frameworks for appropriate, sustainable antimicrobial treatment is hampered by a scarcity of tangible outcome-based measures of the damage it causes. In this Personal View, a mathematically grounded, outcome-based measure of antimicrobial treatment appropriateness, called imprecision, is proposed. We outline a framework for policy makers and health-care leaders to use this metric to deliver more effective antimicrobial stewardship interventions to future patient pathways. This will be achieved using learning antimicrobial systems built on public and practitioner engagement; solid implementation science; advances in artificial intelligence; and changes to regulation, research, and development. The outcomes of this framework would be more ecologically and organisationally sustainable patterns of antimicrobial development, regulation, and prescribing. We discuss practical, ethical, and regulatory considerations involved in the delivery of novel antimicrobial drug development, and policy and patient pathways built on artificial intelligence-augmented measures of antimicrobial treatment imprecision.
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Antiinfecciosos , Inteligencia Artificial , Humanos , Antiinfecciosos/uso terapéutico , Salud Pública , Instituciones de Salud , PolíticasRESUMEN
The proliferation of various forms of artificial intelligence (AI) brings many opportunities to improve health care. AI models can harness complex evolving data, inform and augment human actions, and learn from health outcomes such as morbidity and mortality. The global public health challenge of antimicrobial resistance (AMR) needs large-scale optimisation of antimicrobial use and wider infection care, which could be enabled by carefully constructed AI models. As AI models become increasingly useful and robust, health-care systems remain challenging places for their deployment. An implementation gap exists between the promise of AI models and their use in patient and population care. Here, we outline an adaptive implementation and maintenance framework for AI models to improve antimicrobial use and infection care as a learning system. The roles of AMR problem identification, law and regulation, organisational support, data processing, and AI development, assessment, maintenance, and scalability in the implementation of AMR-targeted AI models are considered.
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Antibacterianos , Antiinfecciosos , Humanos , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Inteligencia Artificial , Farmacorresistencia Bacteriana , Instituciones de SaludRESUMEN
INTRODUCTION: Non-ventilator-associated hospital-acquired pneumonia (nv-HAP) is the most common healthcare-associated infection (HCAI), is associated with high mortality and morbidity and places a major burden on healthcare systems. Diagnosis currently relies on chest x-rays to confirm pneumonia and sputum cultures to determine the microbiological cause. This approach leads to over-diagnosis of pneumonia, rarely identifies a causative pathogen and perpetuates unnecessary and imprecise antibiotic use. The HAP-FAST study aims to evaluate the feasibility of a randomised trial to evaluate the clinical impact of low-dose, non-contrast-enhanced thoracic CT scans and rapid molecular sputum analysis using the BIOFIRE® FILMARRAY® pneumonia plus panel (FAPP) for patients suspected with nv-HAP. METHODS AND ANALYSIS: The HAP-FAST feasibility study consists of a pilot randomised trial, a qualitative study, a costing analysis and exploratory analyses of clinical samples to investigate the immune-pathophysiology of HAP. Participants are identified and recruited from four acute hospitals in the Northwest of the UK. Using a Research Without Prior Consent model, the pilot trial will recruit 220 adult participants, with or without mental capacity, and with suspected HAP. HAP-FAST is a non-blinded, sequential, multiple assignment, randomised trial with two possible stages of randomisation: first, chest x-ray (CXR) or CT; second, if treated as nv-HAP, FAPP or standard microbiological processing alone (no FAPP). Pathogen-specific antibiotic guidance will be provided for FAPP results. Randomisation uses a web-based platform and followed up for 90 days. The feasibility of a future trial will be determined by assessing trial processes, outcome measures and patient and staff experiences. ETHICS AND DISSEMINATION: This study has undergone combined review by the UK NHS Research Ethics Committee and Health Research Authority. Results will be disseminated via peer-reviewed journals, via the funders' website and through a range of media to engage the public. TRIAL REGISTRATION NUMBER: NCT05483309.
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Antibacterianos , Estudios de Factibilidad , Neumonía Asociada a la Atención Médica , Tomografía Computarizada por Rayos X , Humanos , Antibacterianos/uso terapéutico , Tomografía Computarizada por Rayos X/métodos , Tomografía Computarizada por Rayos X/economía , Proyectos Piloto , Neumonía Asociada a la Atención Médica/diagnóstico por imagen , Neumonía Asociada a la Atención Médica/tratamiento farmacológico , Radiografía Torácica/economía , Radiografía Torácica/métodos , Adulto , Esputo/microbiología , Ensayos Clínicos Controlados Aleatorios como Asunto , Investigación Cualitativa , MasculinoRESUMEN
Maize demand in Sub-Saharan Africa is expected to increase 2.3 times during the next 30 years driven by demographic and dietary changes. Over the past two decades, the area cropped with maize has expanded by 17 million hectares in the region, with limited yield increase. Following this trend could potentially result in further maize cropland expansion and the need for imports to satisfy domestic demand. Here, we use data collected from 14,773 smallholder fields in the region to identify agronomic practices that can improve farm yield gains. We find that agronomic practices related to cultivar selection, and nutrient, pest, and crop management can double on-farm yields and provide an additional 82 million tons of maize within current cropped area. Research and development investments should be oriented towards agricultural practices with proven capacity to raise maize yields in the region.
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Agricultura , Producción de Cultivos , Productos Agrícolas , Zea mays , Zea mays/crecimiento & desarrollo , África del Sur del Sahara , Productos Agrícolas/crecimiento & desarrollo , Producción de Cultivos/estadística & datos numéricos , Producción de Cultivos/métodos , Agricultura/métodos , Abastecimiento de AlimentosRESUMEN
Background: Higher-valency pneumococcal vaccines are anticipated. We aimed to describe serotype distribution and risk factors for vaccine-serotype community-acquired pneumonia (CAP) in the two years pre-SARS-CoV-2 pandemic. Methods: We conducted a prospective cohort study of adults hospitalised with CAP at three UK sites between 2018 and 2020. Pneumococcal serotypes were identified using a 24-valent urinary-antigen assay and blood cultures. Risk factors associated with vaccine-type pneumonia caused by serotypes in the 13-, 15- and 20-valent pneumococcal conjugate vaccines (PCV13, PCV15, PCV20) and 23-valent pneumococcal polysaccharide vaccine (PPV23) were determined from multivariable analysis. Findings: Of 1921 adults hospitalised with CAP, 781 (40.7%, 95% confidence intervals (CI) 38.5-42.9%) had pneumococcal pneumonia. A single PCV13-serotype was detected in 242 (31.0%, 95% CI 27.8-34.3%) pneumococcal CAP patients, mostly serotype 3 (171/242, 70.7%, 95% CI 64.5-76.0%). The additional two PCV15-serotypes were detected in 31 patients (4%, 95% CI 2.8-5.6%), and PCV20-non13-serotypes in 192 (24.6%), with serotype 8 most prevalent (123/192, 64.1%, 95% CI 57.1-70.5%). Compared to PCV13-serotype CAP, people with PCV20-non13 CAP were younger (median age 62 versus 72 years, p < 0.001) and less likely to be male (44% versus 61%, p = 0.01). PPV23-non13-serotypes were found in 252 (32.3%, 95% CI 29.1-35.6%) pneumococcal CAP patients. Interpretation: Despite mature infant pneumococcal programmes, the burden of PCV13-serotype pneumonia remains high in older adults, mainly due to serotype 3. PCV20-non13-serotype pneumonia is more likely in younger people with fewer pneumococcal risk factors. Funding: Unrestricted investigator-initiated research grant from Pfizer, United Kingdom; support from National Institute for Health Research (NIHR) Biomedical Research Centre, Nottingham.
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INTRODUCTION: Sepsis is a common, potentially life-threatening complication of infection. The optimal treatment for sepsis includes prompt antibiotics and intravenous fluids, facilitated by its early and accurate recognition. Currently, clinicians identify and assess severity of suspected sepsis using validated clinical scoring systems. In England, the National Early Warning Score 2 (NEWS2) has been mandated across all National Health Service (NHS) trusts and ambulance organisations. Like many clinical scoring systems, NEWS2 should not be used without clinical judgement to determine either the level of acuity or a diagnosis. Despite this, there is a tendency to overemphasise the score in isolation in patients with suspected infection, leading to the overprescription of antibiotics and potentially treatment-related complications and rising antimicrobial resistance. The biomarker procalcitonin (PCT) has been shown to be useful in specific circumstances to support appropriate antibiotics prescribing by identifying bacterial infection. PCT is not routinely used in the care of undifferentiated patients presenting to emergency departments (EDs), and the evidence base of its optimal usage is poor. The PROcalcitonin and NEWS2 evaluation for Timely identification of sepsis and Optimal (PRONTO) study is a randomised controlled trial (RCT) in adults with suspected sepsis presenting to the ED to compare standard clinical management based on NEWS2 scoring plus PCT-guided risk assessment with standard clinical management based on NEWS2 scoring alone and compare if this approach reduces prescriptions of antibiotics without increasing mortality. METHODS AND ANALYSIS: PRONTO is a parallel two-arm open-label individually RCT set in up to 20 NHS EDs in the UK with a target sample size of 7676 participants. Participants will be randomised in a ratio of 1:1 to standard clinical management based on NEWS2 scoring or standard clinical management based on NEWS2 scoring plus PCT-guided risk assessment. We will compare whether the addition of PCT measurement to NEWS2 scoring can lead to a reduction in intravenous antibiotic initiation in ED patients managed as suspected sepsis, with at least no increase in 28-day mortality compared with NEWS2 scoring alone (in conjunction with local standard care pathways). PRONTO has two coprimary endpoints: initiation of intravenous antibiotics at 3 hours (superiority comparison) and 28-day mortality (non-inferiority comparison). The study has an internal pilot phase and group-sequential stopping rules for effectiveness and futility/safety, as well as a qualitative substudy and a health economic evaluation. ETHICS AND DISSEMINATION: The trial protocol was approved by the Health Research Authority (HRA) and NHS Research Ethics Committee (Wales REC 2, reference 20/WA/0058). In England and Wales, the law allows the use of deferred consent in approved research situations (including ED studies) where the time dependent nature of intervention would not allow true informed consent to be obtained. PRONTO has approval for a deferred consent process to be used. Findings will be disseminated through peer-reviewed journals and presented at scientific conferences. TRIAL REGISTRATION NUMBER: ISRCTN54006056.
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Infecciones Bacterianas , Sepsis , Adulto , Antibacterianos/uso terapéutico , Infecciones Bacterianas/tratamiento farmacológico , Servicio de Urgencia en Hospital , Humanos , Estudios Multicéntricos como Asunto , Polipéptido alfa Relacionado con Calcitonina , Ensayos Clínicos Controlados Aleatorios como Asunto , Sepsis/diagnóstico , Sepsis/tratamiento farmacológicoRESUMEN
BACKGROUND: NHS England recommends non-invasive continuous positive airway pressure (CPAP) as a possible treatment for type 1 respiratory failure associated with COVID-19 pneumonitis, either to avoid intubation or as a ceiling of care. However, data assessing this strategy are sparse, especially for the use of CPAP as a ceiling of care, and particularly when delivered outside of a traditional critical care environment. We describe a cohort of patients from Liverpool, UK, who received CPAP on a dedicated respiratory surge unit at the start of the second wave of the COVID-19 pandemic in UK. METHODS: Retrospective cohort analysis of consecutive patients receiving CPAP for the treatment of respiratory failure secondary to COVID-19 on the respiratory surge unit at the Royal Liverpool Hospital, Liverpool, UK from 21 September until 30 November 2020. RESULTS: 88 patients were included in the analysis. 56/88 (64%) were deemed suitable for escalation to invasive mechanical ventilation (IMV) and received CPAP as a trial; 32/88 (36%) received CPAP as a ceiling of care. Median age was 63 years (IQR: 56-74) and 58/88 (66%) were men. Median SpO2/FiO2 immediately prior to CPAP initiation was 95 (92-152). Among patients for escalation to IMV, the median time on CPAP was 6 days (IQR 4-7) and survival at day 30 was 84% (47/56) with 14/56 (25%) escalated to IMV. Of those patients for whom CPAP was ceiling of care, the median duration of CPAP was 9 days (IQR 7-11) and 18/32 (56%) survived to day 30. Pulmonary barotrauma occurred in 9% of the cohort. There were no associations found on multivariant analysis that were associated with all-cause 30-day mortality. CONCLUSIONS: With adequate planning and resource redistribution, CPAP may be delivered effectively outside of a traditional critical care setting for the treatment of respiratory failure due to COVID-19. Clinicians delivering CPAP to patients with COVID-19 pneumonitis should be alert to the dangers of pulmonary barotrauma. Among patients who are for escalation of care, the use of CPAP may avoid the need for IMV in some patients. Our data support the NHS England recommendation to consider CPAP as a ceiling of care.
Asunto(s)
COVID-19 , Presión de las Vías Aéreas Positiva Contínua , Anciano , COVID-19/terapia , Cuidados Críticos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pandemias , Estudios Retrospectivos , Reino Unido/epidemiologíaRESUMEN
The COVID-19 pandemic has led to a dramatic increase in patients presenting with type 1 respiratory failure. In order to protect our limited critical care capacity, we rapidly developed a new ward-based inpatient continuous positive airway pressure (CPAP) service with direct input from the respiratory, infectious diseases and critical care teams. Close collaboration between these specialties and new innovative solutions were required to facilitate this. CPAP equipment (normally reserved for domiciliary care) was adapted to reduce the pressure on our strained oxygen infrastructure. Side rooms on the infectious diseases ward were swiftly converted into new negative pressure areas using temporary installed ventilatory equipment, reducing the viral aerosol risk for staff. Novel patient monitoring solutions were used to protect staff while also ensuring patient safety. Staff training and specialist oversight was organised within days. The resulting service was successful, with over half (17/26 (65%)) of patients avoiding invasive ventilation.