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BACKGROUND: The SARS-CoV-2 pandemic has caused an unprecedented strain on healthcare systems worldwide, including the United Kingdom National Health Service (NHS). We conducted an observational cohort study of SARS-CoV-2 infection in frontline healthcare workers (HCW) working in an acute NHS Trust during the first wave of the pandemic, to answer emerging questions surrounding SARS-CoV-2 infection, diagnosis, transmission and control. METHODS: Using self-collected weekly saliva and twice weekly combined oropharyngeal/nasopharyngeal (OP/NP) samples, in addition to self-assessed symptom profiles and isolation behaviours, we retrospectively compared SARS-CoV-2 detection by RT-qPCR of saliva and OP/NP samples. We report the association with contemporaneous symptoms and isolation behaviour. RESULTS: Over a 12-week period from 30th March 2020, 40·0% (n = 34/85, 95% confidence interval 31·3-51·8%) HCW had evidence of SARS-CoV-2 infection by surveillance OP/NP swab and/or saliva sample. Symptoms were reported by 47·1% (n = 40) and self-isolation by 25·9% (n = 22) participants. Only 44.1% (n = 15/34) participants with SARS-CoV-2 infection reported any symptoms within 14 days of a positive result and only 29·4% (n = 10/34) reported self-isolation periods. Overall agreement between paired saliva and OP/NP swabs was 93·4% (n = 211/226 pairs) but rates of positive concordance were low. In paired samples with at least one positive result, 35·0% (n = 7/20) were positive exclusively by OP/NP swab, 40·0% (n = 8/20) exclusively by saliva and in only 25·0% (n = 5/20) were the OP/NP and saliva result both positive. CONCLUSIONS: HCW are a potential source of SARS-CoV-2 transmission in hospitals and symptom screening will identify the minority of infections. Without routine asymptomatic SARS-CoV-2 screening, it is likely that HCW with SARS-CoV-2 infection would continue to attend work. Saliva, in addition to OP/NP swab testing, facilitated ascertainment of symptomatic and asymptomatic SARS-CoV-2 infections. Combined saliva and OP/NP swab sampling would improve detection of SARS-CoV-2 for surveillance and is recommended for a high sensitivity strategy.
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COVID-19 , Saliva , Humanos , COVID-19/diagnóstico , SARS-CoV-2 , Estudios de Cohortes , Estudios Retrospectivos , Medicina Estatal , Personal de Salud , Manejo de Especímenes , NasofaringeRESUMEN
BACKGROUND: Cases of human monkeypox are rarely seen outside of west and central Africa. There are few data regarding viral kinetics or the duration of viral shedding and no licensed treatments. Two oral drugs, brincidofovir and tecovirimat, have been approved for treatment of smallpox and have demonstrated efficacy against monkeypox in animals. Our aim was to describe the longitudinal clinical course of monkeypox in a high-income setting, coupled with viral dynamics, and any adverse events related to novel antiviral therapies. METHODS: In this retrospective observational study, we report the clinical features, longitudinal virological findings, and response to off-label antivirals in seven patients with monkeypox who were diagnosed in the UK between 2018 and 2021, identified through retrospective case-note review. This study included all patients who were managed in dedicated high consequence infectious diseases (HCID) centres in Liverpool, London, and Newcastle, coordinated via a national HCID network. FINDINGS: We reviewed all cases since the inception of the HCID (airborne) network between Aug 15, 2018, and Sept 10, 2021, identifying seven patients. Of the seven patients, four were men and three were women. Three acquired monkeypox in the UK: one patient was a health-care worker who acquired the virus nosocomially, and one patient who acquired the virus abroad transmitted it to an adult and child within their household cluster. Notable disease features included viraemia, prolonged monkeypox virus DNA detection in upper respiratory tract swabs, reactive low mood, and one patient had a monkeypox virus PCR-positive deep tissue abscess. Five patients spent more than 3 weeks (range 22-39 days) in isolation due to prolonged PCR positivity. Three patients were treated with brincidofovir (200 mg once a week orally), all of whom developed elevated liver enzymes resulting in cessation of therapy. One patient was treated with tecovirimat (600 mg twice daily for 2 weeks orally), experienced no adverse effects, and had a shorter duration of viral shedding and illness (10 days hospitalisation) compared with the other six patients. One patient experienced a mild relapse 6 weeks after hospital discharge. INTERPRETATION: Human monkeypox poses unique challenges, even to well resourced health-care systems with HCID networks. Prolonged upper respiratory tract viral DNA shedding after skin lesion resolution challenged current infection prevention and control guidance. There is an urgent need for prospective studies of antivirals for this disease. FUNDING: None.
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Mpox , Adulto , Animales , Antivirales/uso terapéutico , Niño , Femenino , Humanos , Masculino , Mpox/diagnóstico , Mpox/tratamiento farmacológico , Mpox/epidemiología , Estudios Prospectivos , Estudios Retrospectivos , Reino Unido/epidemiologíaRESUMEN
BACKGROUND: Vitamin D deficiency has been associated with worse coronavirus disease 2019 (COVID-19) outcomes, but circulating 25-hydroxyvitamin D [25(OH)D] is largely bound to vitamin D-binding protein (DBP) or albumin, both of which tend to fall in illness, making the 25(OH)D status hard to interpret. Because of this, measurements of unbound ("free") and albumin-bound ("bioavailable") 25(OH)D have been proposed. OBJECTIVES: We aimed to examine the relationship between vitamin D status and mortality from COVID-19. METHODS: In this observational study conducted in Liverpool, UK, hospitalized COVID-19 patients with surplus sera available for 25(OH)D analysis were studied. Clinical data, including age, ethnicity, and comorbidities, were extracted from case notes. Serum 25(OH)D, DBP, and albumin concentrations were measured. Free and bioavailable 25(OH)D were calculated. Relationships between total, free, and bioavailable 25(OH)D and 28-day mortality were analyzed by logistic regression. RESULTS: There were 472 patients with COVID-19 included, of whom 112 (23.7%) died within 28 days. Nonsurvivors were older (mean age, 73 years; range, 34-98 years) than survivors (mean age, 65 years; range, 19-95 years; P = 0.003) and were more likely to be male (67%; P = 0.02). The frequency of vitamin D deficiency [25(OH)D < 50 nmol/L] was similar between nonsurvivors (71/112; 63.4%) and survivors (204/360; 56.7%; P = 0.15) but, after adjustments for age, sex, and comorbidities, increased odds for mortality were present in those with severe deficiency [25(OH)D < 25 nmol/L: OR, 2.37; 95% CI, 1.17-4.78] or a high 25(OH)D (≥100 nmol/L; OR, 4.65; 95% CI, 1.51-14.34) compared with a 25(OH)D value of 50-74 nmol/L (reference). Serum DBP levels were not associated with mortality after adjustments for 25(OH)D, age, sex, and comorbidities. Neither free nor bioavailable 25(OH)D values were associated with mortality. CONCLUSIONS: Vitamin D deficiency, as commonly defined by serum 25(OH)D levels (<50 nmol/L), is not associated with increased mortality from COVID-19, but extremely low (<25 nmol/L) and high (>100 nmol/L) levels may be associated with mortality risks. Neither free nor bioavailable 25(OH)D values are associated with mortality risk. The study protocol was approved by the London-Surrey Research Ethics Committee (20/HRA/2282).
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COVID-19 , Deficiencia de Vitamina D , Anciano , Albúminas/metabolismo , Femenino , Humanos , Masculino , Vitamina D , Deficiencia de Vitamina D/complicaciones , Proteína de Unión a Vitamina D , VitaminasRESUMEN
Despite huge advances in vaccines, testing and treatments for COVID-19, there is negligible evidence on the perceptions of people hospitalised with COVID-19 about the care they received. To address this, we developed a satisfaction survey for people with COVID-19 admitted to our hospital during the first COVID-19 wave in Liverpool. Of those invited, 98/160 (61%) responded, of whom 94/98 (96%) completed the survey. Respondents rated overall care highly (mean 4.7/5) and 89/94 (95%) reported that they would recommend the hospital to friends and/or family. Most respondents felt safe on the ward (94%), with privacy maintained (93%) and pain well managed (90%). Fewer than two-thirds (63%) of respondents considered themselves adequately consulted regarding medications and side effects. Sleep and food/drink quality were also highlighted as areas for improvement. To overcome the issues raised, we generated a 'COVID-19 practice pointers' poster within an integrated educational bundle on COVID-19 wards. The impact of the bundle on perceptions of people hospitalised with COVID-19 will be evaluated in people hospitalised with COVID-19 in Liverpool in 2021. Whether hospitalised for COVID-19 or other conditions, our survey results are a timely reminder of the importance of involving patients in shaping the care that they receive.
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BACKGROUND: Clinical coding is an integral part of primary care. Disease incidence studies based on primary care electronic health records (EHRs) rely on the accuracy of these codes. Current code validation methods are not appropriate for non-specific conditions and provide limited information about GPs' decision-making behaviour around coding. Qualitative methods could offer insight into decision-making behaviour around coding of patients with non-specific conditions. AIM: To investigate the decision-making behaviour of GPs when applying Read codes to non-specific clinical presentations, using Lyme disease as a case example. DESIGN & SETTING: A pilot study was undertaken, involving masked semi-structured interviews of eight GPs in the North West of England. METHOD: Semi-structured interviews were carried out based on 11 clinical cases representative of Lyme disease presentations. Discrete answers were described descriptively. Interview transcripts were analysed using a thematic approach. RESULTS: Themes underpinning GPs' coding behaviour included: GP personal and professional experience; clinical evidence; diagnostic uncertainty; professional integrity and defensive practice; and patient-sourced health information and beliefs. GPs placed Lyme disease on their differential diagnosis list for five cases; in only two cases would GPs select a Lyme disease related Read code. CONCLUSION: GPs were reluctant to code with specific diagnostic Read codes when they were presented with patients with vague or unfamiliar symptomology. This masked questionnaire methodology offers a new approach to validate incidence figures, based on Read codes of non-specific conditions. The reluctance to code poses many problems for primary care EHRs research. Further research is needed to understand what drives GPs' coding behaviour.
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The aim of this case series is to describe and evaluate our experience of continuous positive airway pressure (CPAP) to treat type 1 respiratory failure in patients with COVID-19. CPAP was delivered in negative pressure rooms in the newly repurposed infectious disease unit. We report a cohort of 24 patients with type 1 respiratory failure and COVID-19 admitted to the Royal Liverpool Hospital between 1 April and 30 April 2020. Overall, our results were positive; we were able to safely administer CPAP outside the walls of a critical care or high dependency unit environment and over half of patients (58%) avoided mechanical ventilation and a total of 19 out of 24 (79%) have survived and been discharged from our care.
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Presión de las Vías Aéreas Positiva Contínua/métodos , Infecciones por Coronavirus , Pandemias , Neumonía Viral , Utilización de Procedimientos y Técnicas/estadística & datos numéricos , Unidades de Cuidados Respiratorios , Insuficiencia Respiratoria , Betacoronavirus/aislamiento & purificación , COVID-19 , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/fisiopatología , Infecciones por Coronavirus/terapia , Vías Clínicas/tendencias , Femenino , Humanos , Masculino , Registros Médicos/estadística & datos numéricos , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Consumo de Oxígeno , Neumonía Viral/epidemiología , Neumonía Viral/fisiopatología , Neumonía Viral/terapia , Unidades de Cuidados Respiratorios/métodos , Unidades de Cuidados Respiratorios/organización & administración , Insuficiencia Respiratoria/etiología , Insuficiencia Respiratoria/mortalidad , Insuficiencia Respiratoria/fisiopatología , Insuficiencia Respiratoria/terapia , SARS-CoV-2 , Análisis de Supervivencia , Reino Unido/epidemiologíaRESUMEN
OBJECTIVES: Many secondary care departments receive external advice calls. However, systematic advice-call documentation is uncommon and evidence on call nature and burden infrequent. The Liverpool tropical and infectious disease unit (TIDU) provides specialist advice locally, regionally and nationally. We created and evaluated a recording system to document advice calls received by TIDU. METHODS: An electronic advice-call recording system was created for TIDU specialist trainees to document complex, predominantly external calls. Fourteen months of advice calls were summarised, analysed and recommendations for other departments wishing to replicate this system made. RESULTS: Five-hundred and ninety calls regarding 362 patients were documented. Median patient age was 44 years (interquartile range 29-56 years) and 56% were male. Sixty-nine per cent of patients discussed were referred from secondary healthcare, half from emergency or acute medicine departments; 43% of patients were returning travellers; 59% of returning travellers had undifferentiated fever, one-third of whom returned from sub-Saharan Africa; 32% of patients discussed were further reviewed at TIDU. Interim 6-month review showed good user acceptability of the system. CONCLUSIONS: Implementing an advice-call recording system was feasible within TIDU. Call and follow-up burden was high with advice regarding fever in returned travellers predominating. Similar systems could improve clinical governance, patient care and service delivery in other secondary care departments.
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Enfermedades Transmisibles , Teléfono , Adulto , África del Sur del Sahara , Enfermedades Transmisibles/terapia , Servicio de Urgencia en Hospital , Femenino , Humanos , Masculino , Persona de Mediana Edad , Derivación y ConsultaRESUMEN
BACKGROUND: Primary care is likely to see the highest number of Lyme disease patients. Despite this, there is limited published data regarding Lyme disease patients accessing primary care in the UK. We aim to describe trends in the incidence of a new diagnosis, and demographics of patients identified in a primary care electronic health database. METHODS: A descriptive epidemiological study of Lyme disease coded patients in UK primary care. 3725 patients coded for Lyme disease during 1998-2016 were identified within The Health Improvement Network (THIN). Incidence rates and the demographics of cases identified were described. Poisson regression was used to analyse socio-demographic characteristics of the cases. RESULTS: There was an increase in annual crude incidence rates, peaking in 2015 at 5.47 (95% CI 4.85-6.14) cases per 100,000 population per year. Multivariable analysis showed there were significant differences in the ages of those affected, incidence of a new diagnosis rose as deprivation levels improved, and that there was a higher incidence of cases living in rural areas compared to urban areas. There was no significant difference between sexes for the UK. Cases were significantly more likely to identify with being white compared to the national population. CONCLUSIONS: An increasing incidence of patients newly coded with Lyme disease related Read codes was identified using data from a UK national primary care database. By comparing these incidence figures with national laboratory-confirmed surveillance data, a multiplication factor of 2.35 (95%CI 1.81-2.88) can be calculated in order to estimate the annual number of cases seen in primary care. The significant socio-demographic variables associated with a Lyme disease diagnosis likely reflect a complex interplay of socio-economic issues, which needs to be further explored. Future work is needed to examine the treatment and management of patients within this database.
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Enfermedad de Lyme/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Estudios de Cohortes , Bases de Datos Factuales , Estudios Epidemiológicos , Femenino , Humanos , Incidencia , Lactante , Masculino , Persona de Mediana Edad , Atención Primaria de Salud/estadística & datos numéricos , Reino Unido/epidemiología , Adulto JovenAsunto(s)
Betacoronavirus , Técnicas de Laboratorio Clínico/normas , Infecciones por Coronavirus/diagnóstico , Técnicas para Inmunoenzimas , Neumonía Viral/diagnóstico , Betacoronavirus/genética , Betacoronavirus/inmunología , Betacoronavirus/aislamiento & purificación , COVID-19 , Prueba de COVID-19 , Ensayo de Inmunoadsorción Enzimática , Humanos , Inmunoglobulina G/análisis , Inmunoglobulina M/análisis , Cavidad Nasal/virología , Pandemias , ARN Viral/análisis , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , SARS-CoV-2 , Factores de Tiempo , Esparcimiento de VirusRESUMEN
Understanding local viral hepatitis and HIV epidemiology is essential if WHO elimination targets are to be achieved. We demonstrate a consistently high prevalence of undiagnosed active infection in urban emergency department attendees in England, with variations in local risk groups crucial to informing targeted testing initiatives.
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Infecciones de Transmisión Sanguínea/epidemiología , Servicio de Urgencia en Hospital/estadística & datos numéricos , Hospitales Urbanos/estadística & datos numéricos , Enfermedades no Diagnosticadas/epidemiología , Virosis/epidemiología , Adulto , Infecciones de Transmisión Sanguínea/diagnóstico , Infecciones de Transmisión Sanguínea/virología , Inglaterra/epidemiología , Femenino , Humanos , Masculino , Tamizaje Masivo , Persona de Mediana Edad , Prevalencia , Factores de Riesgo , Estudios Seroepidemiológicos , Enfermedades no Diagnosticadas/virología , Virosis/diagnósticoRESUMEN
In early September 2018, two cases of monkeypox were reported in the United Kingdom (UK), diagnosed on 7 September in Cornwall (South West England) and 11 September in Blackpool (North West England). The cases were epidemiologically unconnected and had recently travelled to the UK from Nigeria, where monkeypox is currently circulating. We describe the epidemiology and the public health response for the first diagnosed cases outside the African continent since 2003.
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Enfermedades Transmisibles Emergentes/virología , Monkeypox virus/aislamiento & purificación , Mpox/diagnóstico , Viaje , Animales , Enfermedades Transmisibles Emergentes/diagnóstico , Enfermedades Transmisibles Emergentes/epidemiología , Enfermedades Transmisibles Emergentes/transmisión , Trazado de Contacto , Humanos , Mpox/virología , Nigeria/epidemiología , Infecciones por Poxviridae/microbiología , Infecciones por Poxviridae/transmisión , Salud Pública , Medición de Riesgo , Reino UnidoRESUMEN
The importance of appropriate personal protective equipment (PPE) as a component of healthcare worker (HCW) protection was highlighted during the Ebola virus disease (EVD) outbreak in West Africa. The large number of HCW deaths in Africa was in part due to lack of resources or prior training in PPE usage. As part of the Ebola legacy, the High Consequence Infectious Disease (HCID) programme was initiated by NHS England and Public Health England (PHE) to improve preparedness for Ebola and other infections that not only endanger the life of the patient, but also pose particular dangers to HCWs. A systematic review identified national standardisation of PPE protocols as a priority, but recognised that a lack of safety data limited the ability to mandate any one protocol. A simulation-based exercise was developed to assess the safety of PPE ensembles in use in the UK during first assessment of a patient with a possible HCID. A mannequin was adapted to expose volunteer HCWs to synthetic bodily fluids (vomit, sweat, diarrhoea and cough), each with a different coloured fluorescent tracer, invisible other than under ultraviolet (UV) light. After exposure, HCWs were examined under UV lights to locate fluorescent contamination, and were screened again after removing PPE (doffing) to detect any personal contamination. The exercise was videoed, allowing retrospective analysis of contamination events and user errors. The simulation testing identified significant HCW contamination events after doffing, related to protocol failure or complications in PPE doffing, providing conclusive evidence that improvements could be made. At a workshop with an expert stakeholder group, the data were examined and a unified PPE ensemble agreed. This ensemble was then tested in the same simulation exercise and no evidence of any HCW contamination was seen after doffing. Following further review by the working group, a consensus agreement has been reached and a unified 'HCID assessment PPE' ensemble, with accompanying donning and doffing protocols, is presented here.
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Brotes de Enfermedades/prevención & control , Control de Infecciones/organización & administración , Transmisión de Enfermedad Infecciosa de Paciente a Profesional/prevención & control , Equipo de Protección Personal , África , Consenso , Infección Hospitalaria/prevención & control , Inglaterra , Personal de Salud/educación , Fiebre Hemorrágica Ebola/prevención & control , Humanos , Control de Infecciones/métodos , Servicios de Salud del Trabajador/métodos , Servicios de Salud del Trabajador/organización & administración , Estudios Retrospectivos , Encuestas y CuestionariosRESUMEN
OBJECTIVES: New point of care diagnostics are urgently needed to reduce the over-prescription of antimicrobials for bacterial respiratory tract infection (RTI). We performed a pilot cross sectional study to assess the feasibility of gas-capillary column ion mobility spectrometer (GC-IMS), for the analysis of volatile organic compounds (VOC) in exhaled breath to diagnose bacterial RTI in hospital inpatients. METHODS: 71 patients were prospectively recruited from the Acute Medical Unit of the Royal Liverpool University Hospital between March and May 2016 and classified as confirmed or probable bacterial or viral RTI on the basis of microbiologic, biochemical and radiologic testing. Breath samples were collected at the patient's bedside directly into the electronic nose device, which recorded a VOC spectrum for each sample. Sparse principal component analysis and sparse logistic regression were used to develop a diagnostic model to classify VOC spectra as being caused by bacterial or non-bacterial RTI. RESULTS: Summary area under the receiver operator characteristic curve was 0.73 (95% CI 0.61-0.86), summary sensitivity and specificity were 62% (95% CI 41-80%) and 80% (95% CI 64-91%) respectively (p = 0.00147). CONCLUSIONS: GC-IMS analysis of exhaled VOC for the diagnosis of bacterial RTI shows promise in this pilot study and further trials are warranted to assess this technique.
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Infecciones Bacterianas/diagnóstico , Nariz Electrónica , Metabolómica , Infecciones del Sistema Respiratorio/diagnóstico , Compuestos Orgánicos Volátiles/análisis , Anciano , Infecciones Bacterianas/microbiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Curva ROC , Infecciones del Sistema Respiratorio/microbiologíaRESUMEN
PURPOSE OF REVIEW: The review examines the changing causes and the investigation of infectious and noninfectious diarrhoea in individuals with HIV. RECENT FINDINGS: Despite the excellent prognosis conferred by combination antiretroviral therapy, diarrhoea is still common in HIV-positive individuals and is associated with reduced quality of life and survival. There is increasing interest in the importance of Th17 and Th22 T cells in the maintenance of mucosal immunity within the gut, and in the role of the gut microbiome in gut homeostasis. Bacterial causes of HIV-associated diarrhoea continue to be important in resource-poor settings. In other settings, sexually transmitted enteric infections such as lymphogranuloma venereum and shigellosis are increasingly reported in men who have sex with men. HIV increases the risk of such infections and the presence of antimicrobial resistance. Parasitic causes of diarrhoea are more common in individuals with uncontrolled HIV and low CD4 counts. Noninfectious causes of diarrhoea include all classes of antiretroviral therapy, which is under-recognised as a cause of poor treatment adherence. Pancreatic dysfunction is remediable and the diagnostic workup of HIV-related diarrhoea should include faecal elastase measurements. New antimotility agents such as crofelemer may be useful in managing secretory diarrhoea symptoms. SUMMARY: Clinicians looking after patients with HIV should ask about diarrhoeal symptoms, which are under-reported and may have a remediable infectious or noninfectious cause.
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Diarrea , Infecciones por VIH , Fármacos Anti-VIH/uso terapéutico , Diarrea/complicaciones , Diarrea/terapia , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , VIH-1 , HumanosRESUMEN
It is not always possible to administer antituberculosis pharmacotherapy orally for reasons that may be a direct consequence of tuberculosis itself. To our knowledge, no published literature is available regarding antituberculosis drug absorption via feeding tube. We present the case of a patient with tuberculosis meningitis who required medication administration via percutaneous endoscopic jejunostomy (PEJ) tube. Blood samples were collected during the continuation phase of antituberculosis therapy, immediately before dose administration, and then at 1, 2, 4, and 6 hours after dose administration for quantification of serum rifampin concentrations. Assaying these concentrations by high-pressure liquid chromatography demonstrated a peak serum rifampin level (C(max)) of 18 µg/ml and total rifampin exposure (area under the curve from 0-6 hours [AUC(0-6)]) of 50.1 µg/ml. These are high compared with rifampin C(max) and AUC(0-6) values reported in patients after oral rifampin administration; C(max) tends to range between 4.0-10.5 µg/ml and AUC(0-6) 7.0-52.9 µg/ml after oral administration of 600 mg at steady state. Based on our patient's results, therefore, rifampin administered by PEJ tube appears to be well absorbed, with preservation of adequate C(max) and AUC values. It is worth noting that this was in the context of drug administration in the fasted state. In the absence of any published evidence of adequate absorption via jejunal feeding tube in the nonfasted state, it would seem prudent to ensure that patients are fasted when rifampin is administered via PEJ tube, just as patients are when oral rifampin is administered. This report represents the first documented evidence, to our knowledge, of adequate rifampin absorption when administered via PEJ tube and provides important reassurance for health care providers, patients, and families facing similar clinical scenarios.
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Antibióticos Antituberculosos/administración & dosificación , Endoscopía Gastrointestinal/efectos adversos , Absorción Intestinal , Yeyunostomía/efectos adversos , Rifampin/administración & dosificación , Tuberculosis Meníngea/tratamiento farmacológico , Administración a través de la Mucosa , Antibióticos Antituberculosos/sangre , Antibióticos Antituberculosos/farmacocinética , Antibióticos Antituberculosos/uso terapéutico , Trastornos de Deglución/etiología , Trastornos de Deglución/cirugía , Humanos , Mucosa Intestinal/metabolismo , Yeyuno/metabolismo , Masculino , Persona de Mediana Edad , Rifampin/sangre , Rifampin/farmacocinética , Rifampin/uso terapéutico , Tuberculosis Meníngea/sangre , Tuberculosis Meníngea/metabolismo , Tuberculosis Meníngea/fisiopatologíaRESUMEN
BACKGROUND: Mannose-binding lectin (MBL) plays a key role in the activation of the lectin-complement pathway of innate immunity, and its deficiency has been linked with several acute infections. However, its role in predisposing to, or modulating disease severity in, Clostridium difficile infection (CDI) has not been investigated. METHODS: We prospectively recruited 308 CDI case patients and 145 control patients with antibiotic-associated diarrhea (AAD). CDI outcome measures were disease severity, duration of symptoms, 30-day mortality, and 90-day recurrence. Serum concentrations of MBL were determined using a commercial enzyme-linked immunosorbent assay transferred to an electrochemiluminescence-based platform. MBL2 polymorphisms were typed using a combination of pyrosequencing and TaqMan genotyping assays. RESULTS: The frequency of the MBL2 genetic variants was similar to that reported in other white populations. MBL serum concentrations in CDI and AAD subjects were determined by MBL2 exonic variants B, C, and D and the haplotypes (LYPB, LYQC, and HYPD). There was no difference in either MBL concentrations or genotypes between cases and controls. MBL concentration, but not genotype, was a determinant of CDI recurrence (odds ratios, 3.18 [95% confidence interval {CI}, 1.40-7.24] and 2.61 [95% CI, 1.35-5.04] at the <50 ng/mL and <100 ng/mL cutoff points, respectively; P < .001). However, neither MBL concentration nor MBL2 genotype was linked with the other CDI outcomes. CONCLUSIONS: Serum MBL concentration did not differentiate between CDI cases and AAD controls, but among CDI cases, MBL concentration, but not genotype, was associated with CDI recurrence, indicating that MBL acts as a modulator of disease, rather than a predisposing factor.
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Clostridioides difficile , Infecciones por Clostridium/sangre , Enterocolitis Seudomembranosa/sangre , Lectina de Unión a Manosa/sangre , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Infecciones por Clostridium/microbiología , Comorbilidad , Enterocolitis Seudomembranosa/etiología , Enterocolitis Seudomembranosa/microbiología , Femenino , Frecuencia de los Genes , Orden Génico , Sitios Genéticos , Genotipo , Haplotipos , Humanos , Masculino , Lectina de Unión a Manosa/genética , Persona de Mediana Edad , Evaluación del Resultado de la Atención al Paciente , Polimorfismo Genético , Estudios Prospectivos , Isoformas de Proteínas , Recurrencia , Valores de ReferenciaRESUMEN
Measurement of both calprotectin and lactoferrin in faeces has successfully been used to discriminate between functional and inflammatory bowel conditions, but evidence is limited for Clostridium difficile infection (CDI). We prospectively recruited a cohort of 164 CDI cases and 52 controls with antibiotic-associated diarrhoea (AAD). Information on disease severity, duration of symptoms, 30-day mortality and 90-day recurrence as markers of complicated CDI were recorded. Specimens were subject to microbiological culture and PCR-ribotyping. Levels of faecal calprotectin (FC) and lactoferrin (FL) were measured by ELISA. Statistical analysis was conducted using percentile categorisation. ROC curve analysis was employed to determine optimal cut-off values. Both markers were highly correlated with each other (r2â=â0.74) and elevated in cases compared to controls (p<0.0001; ROC>0.85), although we observed a large amount of variability across both groups. The optimal case-control cut-off point was 148 mg/kg for FC and 8.1 ng/µl for FL. Median values for FL in CDI cases were significantly greater in patients suffering from severe disease compared to non-severe disease (104.6 vs. 40.1 ng/µl, pâ=â0.02), but were not significant for FC (969.3 vs. 512.7 mg/kg, pâ=â0.09). Neither marker was associated with 90-day recurrence, prolonged CDI symptoms, positive culture results and colonisation by ribotype 027. Both FC and FL distinguished between CDI cases and AAD controls. Although FL was associated with disease severity in CDI patients, this showed high inter-individual variability and was an isolated finding. Thus, FC and FL are unlikely to be useful as biomarkers of complicated CDI disease.
Asunto(s)
Infecciones por Clostridium/metabolismo , Enterocolitis Seudomembranosa/metabolismo , Heces/química , Lactoferrina/metabolismo , Complejo de Antígeno L1 de Leucocito/metabolismo , Anciano , Biomarcadores/metabolismo , Estudios de Casos y Controles , Clostridioides difficile , Infecciones por Clostridium/microbiología , Enterocolitis Seudomembranosa/microbiología , Femenino , Humanos , Masculino , Estudios Prospectivos , Ribotipificación/métodosRESUMEN
INTRODUCTION: Chronic hepatitis B virus and schistosomiasis are independently associated with significant mortality and morbidity worldwide. Despite much geographic overlap between these conditions and no reason why co-infection should not exist, we present what is, to the best of our knowledge, the first published report of a proven histological diagnosis of hepatic Schistosomiasis japonicum and chronic hepatitis B co-infection. A single case of hepatitis B and hepatic Schistosomiasis mansoni diagnosed by liver biopsy has previously been reported in the literature. CASE PRESENTATION: A 38-year-old Chinese man with known chronic hepatitis B virus infection presented with malaise, nausea and headache. Blood tests revealed increased transaminases and serology in keeping with hepatitis B virus e-antigen seroconversion. A liver biopsy was performed because some investigations, particularly transient elastography, suggested cirrhosis. Two schistosome ova were seen on liver histology, identified as S. japonicum, probably acquired in China as a youth. His peripheral eosinophil count was normal, schistosomal serology and stool microscopy for ova, cysts and parasites were negative. CONCLUSION: Hepatic schistosomiasis co-infection should be considered in patients with hepatitis B virus infection who are from countries endemic for schistosomiasis. Screening for schistosomiasis using a peripheral eosinophil count, schistosomal serology and stool microscopy may be negative despite infection, therefore presumptive treatment could be considered. Transient elastography should not be used to assess liver fibrosis during acute flares of viral hepatitis because readings are falsely elevated. The impact of hepatic schistosomiasis on the sensitivity and specificity of transient elastography measurement for the assessment of hepatitis B is as yet unknown.