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Reproduction by egg-laying (oviparity) or live-bearing (viviparity) is a genetically determined trait fundamental to the biology of amniotes. Squamates are an emerging model for the genetics of reproductive mode yet lack cell culture models valuable for exploring molecular mechanisms. Here, we report a novel primary culture model for reproductive biology: cell cultures derived from the oviduct tissues (infundibulum, uterus and vagina) of oviparous and viviparous common lizards (Lacertidae: Zootoca vivipara). We maintained and expanded these cultures for over 100 days, including repeated subculturing and successful revival of cryopreserved cells. Immunocytochemical investigation suggested expression of both epithelial and fibroblast-like proteins, and RNA sequencing of cultured cells as compared to in vivo oviduct tissue showed changes in gene expression in response to the cell culture environment. Despite this, we confirmed the maintenance of distinct gene expression patterns in viviparous and oviparous cells after 60+ days of cell culture, finding 354 differentially expressed genes between viviparous and oviparous cells. Furthermore, we confirmed the expression of 15 viviparity-associated candidate genes in cells maintained for 60+ days in culture. Our study demonstrates the feasibility and utility of oviduct cell culture for molecular analysis of reproductive mode and provides a tool for future genetic experiments.
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INTRODUCTION: In conditionally automated driving, drivers are allowed to engage in non-driving related tasks (NDRTs) and are occasionally requested to take over vehicle control in situations that the automation system cannot handle. Drivers may not be able to adequately perform such requests if they have limited driving experience. This study investigates the influence of driving experience on takeover performance in conditionally automated driving. METHOD: Nineteen subjects participated in this driving simulator study. The NDRTs consisted of three tasks: writing business emails (working condition), watching videos (entertaining condition), and taking a break with eyes closed (resting condition). These three NDRTs require drivers to invest high, moderate, and low levels of mental workload, respectively. The duration of engagement in each NDRT before a takeover request (TOR) was either 5 minutes (short interval) or 30 minutes (long interval). RESULTS: Drivers' driving experience and performance during the control period are highly correlated with their TOR performance. Furthermore, the type and duration of NDRT influence TOR performance, and inexperienced drivers exhibit poorer TOR performance than experienced drivers. CONCLUSIONS AND PRACTICAL APPLICATIONS: These findings have relevance for the types of NDRTs that ought to be permitted during automated driving, the design of automated driving systems, and the formulation of regulations regarding the responsible use of automated vehicles.
Subject(s)
Automobile Driving , Humans , Automation , Reaction TimeABSTRACT
The sound absorption coefficient (SAC) of materials measured in a reverberation room is affected by both the intrinsic properties of the material and geometrical dimensions of the sample. A different size of the same material may produce a different SAC primarily due to the edge effect phenomenon. In this research, the experimental data from multiple laboratories was analyzed to evaluate the influence of the edge effect. An empirical function was established based on these measurement data and the linear relationship between the SAC and the relative edge length. Thomasson's method, the two geometric methods, and the analytical method were used to estimate the SAC of an absorber from measurements on a different size sample and compared with results obtained using the empirical function. The results show that the proposed empirical method is a reliable way to predict the SAC of a sample from measurements on a different size sample of the same material, which only requires the thickness, density, and size of the material.
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OBJECTIVE: To evaluate a triage algorithm used to identify and isolate patients with suspected COVID-19 among medical patients needing admission to hospital using simple clinical criteria and the FebriDx assay. DESIGN: Retrospective observational cohort. SETTING: Large acute National Health Service hospital in London, UK. PARTICIPANTS: All medical admissions from the emergency department between 10 August 2020 and 4 November 2020 with a valid SARS-CoV-2 RT-PCR result. INTERVENTIONS: Medical admissions were triaged as likely, possible or unlikely COVID-19 based on clinical criteria. Patients triaged as possible COVID-19 underwent FebriDx lateral flow assay on capillary blood, and those positive for myxovirus resistance protein A (a host response protein) were managed as likely COVID-19. PRIMARY OUTCOME MEASURES: Diagnostic accuracy (sensitivity, specificity and predictive values) of the algorithm and the FebriDx assay using SARS-CoV-2 RT-PCR from nasopharyngeal swabs as the reference standard. RESULTS: 4.0% (136) of 3443 medical admissions had RT-PCR confirmed COVID-19. Prevalence of COVID-19 was 46% (80/175) in those triaged as likely, 4.1% (50/1225) in possible and 0.3% (6/2033) in unlikely COVID-19. Using a SARS-CoV-2 RT-PCR reference standard, clinical triage had sensitivity of 96% (95% CI 91% to 98%) and specificity of 61.5% (95% CI 59.8% to 63.1%), while the triage algorithm including FebriDx had sensitivity of 93% (95% CI 87% to 96%) and specificity of 86.4% (95% CI 85.2% to 87.5%). While 2033 patients were deemed not to require isolation using clinical criteria alone, the addition of FebriDx to clinical triage allowed a further 826 patients to be released from isolation, reducing the need for isolation rooms by 9.5 per day, 95% CI 8.9 to 10.2. Ten patients missed by the algorithm had mild or asymptomatic COVID-19. CONCLUSIONS: A triage algorithm including the FebriDx assay had good sensitivity and was useful to 'rule-out' COVID-19 among medical admissions to hospital.
Subject(s)
COVID-19 , Algorithms , Cohort Studies , Humans , Point-of-Care Systems , Retrospective Studies , SARS-CoV-2 , Sensitivity and Specificity , State Medicine , TriageABSTRACT
We investigated a COVID-19 outbreak of the SARS-CoV-2 Delta variant of concern in a London care home, where 8/21 residents and 14/21 staff had received a single dose of Vaxzevria (ChAdOx1-S; AstraZeneca) vaccine. We identified 24 SARS-CoV-2 infections (16 residents, 8 staff) among 40 individuals (19 residents, 21 staff); four (3 residents, 1 staff) were hospitalised, and none died. The attack rate after one vaccine dose was 35.7% (5/14) for staff and 81.3% (13/16) for residents.
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COVID-19 , SARS-CoV-2 , COVID-19 Vaccines , Disease Outbreaks , England , Humans , London/epidemiology , VaccinationABSTRACT
BACKGROUND: The World Health Organisation states that the chest x-ray (CXR) has a 'high sensitivity for pulmonary tuberculosis (TB)' [1] and as such, is relied on worldwide as the cornerstone of screening for active pulmonary TB (pTB). METHOD: This is a retrospective analysis of plain chest radiographs and microbiological yield in all patients who were diagnosed with pTB or intra-thoracic nodal tuberculosis (ITLN) in two London NHS Trusts. RESULTS: Between 2011 and 2017 8% of those diagnosed with pTB and 32% with ITLN TB had normal CXR appearances in the 6 weeks preceding diagnosis. DISCUSSION: Pulmomary TB was diagnosed in an additional 51 people based on CT scan and 43 people based on respiratory samples. ITLN TB was also diagnosed in a further 20 people using CT but only an extra 3 people from standard respiratory sampling. Our data suggests that CT imaging and respiratory samples should be sent on all suspected cases of pTB and ITLN TB even if the CXR is normal.
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Bronchoalveolar Lavage Fluid/microbiology , Mycobacterium tuberculosis/isolation & purification , Sputum/microbiology , Tuberculosis, Pulmonary/diagnosis , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Polymerase Chain Reaction/methods , Radiography, Thoracic , Retrospective Studies , Sensitivity and Specificity , Tomography, X-Ray Computed , Tuberculosis, Pulmonary/diagnostic imaging , Young AdultABSTRACT
OBJECTIVES: Our objective was to systematically investigate false-negative histidine-rich protein 2 rapid diagnostic tests (HRP2-RDT) in imported Plasmodium falciparum malaria cases from travelers to the UK and the Republic of Ireland (RoI). METHODS: Five imported malaria cases in travellers returning to the UK and RoI from East Africa were reported to the PHE Malaria Reference Laboratory as negative according to histidine-rich protein (HRP2)-RDT. The cases were systematically investigated using microscopic, RDT, molecular, genomic, and in in vitro approaches. RESULTS: In each case, HRP2-RDT was negative, whereas microscopy confirmed the presence of P. falciparum. Further analysis revealed that the genes encoding HRP2 and HRP3 were deleted in three of the five cases. Whole-genome sequencing in one of these isolates confirmed deletions in P. falciparum chromosomes 8 and 13. Our study produced evidence that the fourth case, which had high parasitemia at clinical presentation, was a rare example of antigen saturation ('prozone-like effect'), leading to a false negative in the HRP2-RDT, while the fifth case was due to low parasitemia. CONCLUSIONS: False-negative HRP2-RDT results with P. falciparum are concerning. Our findings emphasise the necessity of supporting the interpretation of RDT results with microscopy, in conjunction with clinical observations, and sets out a systematic approach to identifying parasites carrying pfhrp2 and pfhrp3 deletions.
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Malaria, Falciparum , Parasites , Animals , Antigens, Protozoan/genetics , Diagnostic Tests, Routine , Gene Deletion , Humans , Ireland/epidemiology , Malaria, Falciparum/diagnosis , Malaria, Falciparum/epidemiology , Plasmodium falciparum/genetics , Protozoan Proteins/genetics , United Kingdom/epidemiologyABSTRACT
Previous studies showed that resources recovery through landfill mining (LFM) is generally challenging from an economic perspective and that a large share of project costs is related to the external treatment and disposal of bulk process wastes such as combustibles and fines residue. Building on these analyses, this study aims to explore the potential for improving the economy of LFM in Europe by creating value from these bulk process wastes. Specifically, the combustibles are treated through internal incineration with subsequent energy recovery, while fines residue is utilized as construction aggregates. These explored possibilities are investigated considering other varying factors at the site, project, and system levels that cover possible LFM project settings in Europe. A set-based modelling approach is adapted to generate multiple LFM scenarios (531,441) and investigate the underlying critical factors that drive the economy of LFM through global sensitivity analysis. Results show that an additional 16% of LFM scenarios become net profitable, mainly driven by fines residue utilization. Avoided costs for re-landfilling are higher than the revenues from construction aggregates. By contrast, internal incineration is driven by the revenues from recovered energy rather than the avoided gate fee, which is substituted by the costs for building and operating own plants. Overall, the policy conditions remain critical to further improve the economy of LFM in Europe. Recommendations include an inclusive quality standard that relies on pollutant leachability rather than total concentration for higher-value application of fines residue and incentive rather than taxation for producing renewable energy from the combustibles.
Subject(s)
Refuse Disposal , Europe , Incineration , Mining , Waste Disposal FacilitiesABSTRACT
OBJECTIVE: The aim of this paper is to describe evolution, epidemiology and clinical outcomes of COVID-19 in subjects tested at or admitted to hospitals in North West London. DESIGN: Observational cohort study. SETTING: London North West Healthcare NHS Trust (LNWH). PARTICIPANTS: Patients tested and/or admitted for COVID-19 at LNWH during March and April 2020 MAIN OUTCOME MEASURES: Descriptive and analytical epidemiology of demographic and clinical outcomes (intensive care unit (ICU) admission, mechanical ventilation and mortality) of those who tested positive for COVID-19. RESULTS: The outbreak began in the first week of March 2020 and reached a peak by the end of March and first week of April. In the study period, 6183 tests were performed in on 4981 people. Of the 2086 laboratory confirmed COVID-19 cases, 1901 were admitted to hospital. Older age group, men and those of black or Asian minority ethnic (BAME) group were predominantly affected (p<0.05). These groups also had more severe infection resulting in ICU admission and need for mechanical ventilation (p<0.05). However, in a multivariate analysis, only increasing age was independently associated with increased risk of death (p<0.05). Mortality rate was 26.9% in hospitalised patients. CONCLUSION: The findings confirm that men, BAME and older population were most commonly and severely affected groups. Only older age was independently associated with mortality.
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COVID-19/epidemiology , Hospitalization , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19/diagnosis , COVID-19/mortality , Child , Child, Preschool , Cohort Studies , Cross-Sectional Studies , Female , Humans , Infant , Infant, Newborn , Intensive Care Units , London/epidemiology , Male , Middle Aged , Respiration, Artificial , Risk Factors , Young AdultABSTRACT
OBJECTIVE: Tuberculosis Drug Induced Liver Injury (TB-DILI) is a common and potentially severe complication associated with anti-tuberculous treatment (ATT). Optimal liver test monitoring for standard TB medication has not been established. We describe the predictive value of pre-treatment liver tests (LTs) and at 2-weeks after initiation of ATT for the detection of TB-DILI. METHODS: Patients initiating ATT were monitored with routine LTs pre-treatment and after 2-weeks. Logistic regression models were constructed to retrospectively identify pre-treatment variables associated with 'late' TB-DILI (>2 weeks after treatment initiation) and whether pre-treatment and 2-week alanine aminotransferase (ALT) levels could predict late TB-DILI. RESULTS: 1247 patients with active tuberculosis managed at 5 sites across north west London between January 2015 and December 2018 were monitored with routine LTs. 103 cases (8.3%) of ATT-associated DILI were diagnosed. 60 cases (58.3%) of TB-DILI occurred later than 2-weeks. The risk of late TB-DILI was 2.2-fold greater for every 30â¯U/L increment in ALT pre-treatment (OR 2.16, 95% CI 1.38-3.29 p<0.001) and 2.1-fold greater for every 30â¯U/L increment in ALT gradient at 2-weeks (OR 2.06, 95% CI 1.52-2.76 p<0.001). CONCLUSION: Routine 2-week LTs capture early TB-DILI and may be valuable in predicting late TB-DILI in patients on ATT.
Subject(s)
Chemical and Drug Induced Liver Injury , Tuberculosis , Antitubercular Agents/adverse effects , Chemical and Drug Induced Liver Injury/diagnosis , Chemical and Drug Induced Liver Injury/drug therapy , Chemical and Drug Induced Liver Injury/etiology , Humans , London , Retrospective Studies , Tuberculosis/diagnosis , Tuberculosis/drug therapyABSTRACT
We describe the London community testing programme developed for COVID-19, audit its effectiveness and report patient acceptability and patient adherence to isolation guidance, based upon a survey conducted with participants.Any patients meeting the Public Health England (PHE) case definition for COVID-19 who did not require hospital admission were eligible for community testing. 2,053 patients with suspected COVID-19 were tested in the community between January and March 2020. Of those tested, 75 (3.6%) were positive. 88% of patients that completed a patient survey felt safe and 82% agreed that community testing was preferable to hospital admission. 97% were able to remain within their own home during the isolation period but just 41% were able to reliably isolate from other members of their household.The London community testing programme allowed widespread testing for COVID-19 while minimising patient transport, hospital admissions and staff exposures. Community testing was acceptable to patients and preferable to admission to hospital. Patients were able to reliably isolate in their home but not from household contacts. The authors believe in the importance, feasibility and acceptability of community testing for COVID-19 as a part of a package of interventions to mitigate a second wave of infection.
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Clinical Laboratory Techniques/statistics & numerical data , Community Health Services/organization & administration , Coronavirus Infections/diagnosis , Mass Screening/organization & administration , Patient Compliance/statistics & numerical data , Pneumonia, Viral/diagnosis , COVID-19 , COVID-19 Testing , Coronavirus Infections/epidemiology , Cross-Sectional Studies , England , Female , Humans , London , Male , Pandemics , Pneumonia, Viral/epidemiology , Program Development , Program Evaluation , Public HealthABSTRACT
INTRODUCTION: Age-related immunosenescence influences the presentation of tuberculosis (TB) in older patients. Here, we explore the clinical and radiological presentation of TB in the elderly and the factors associated with time to treatment for TB. METHODS: This is a retrospective cohort study comparing the clinical, radiological and demographic characteristics of TB patients aged ≥65â years with TB patients aged 18-64â years in a large cohort of TB patients in the UK. Factors associated with the time to presentation and time to treatment were identified using a multivariable analysis model. RESULTS: 1023 patients were included in the analyses: 679 patients aged 18-64â years and 344 patients aged ≥65â years. "Classical" symptoms of TB (cough, haemoptysis, fever, nights sweats and weight loss) were less common among older patients with pulmonary TB (PTB) (p<0.05), but dyspnoea was more common among older patients (p=0.001). Time from presenting in secondary care to starting treatment was shorter in younger compared with older patients: 3 versus 15â days (p=0.001). When adjusted for age, factors associated with shorter time to treatment from symptom onset include sex (male versus female) (hazard ratio (HR) 1.23 (95% CI 1.05-1.46)), UK born (HR 1.23 (95% CI 1.05-1.46)) and HIV (HR 2.07 (95% CI 1.30-3.29)). Only age remained an independent predictor of time to treatment in a multivariable model (HR 0.98 (95% CI 0.98-0.99)). For those with PTB, chest radiography findings showed that cavitation and lymphadenopathy were more common among younger patients (p=0.001). CONCLUSIONS: Older patients aged ≥65â years with TB had fewer "classical" clinical and radiological presentations of TB, which may explain longer times to starting treatment from symptom onset compared with younger patients aged <65â years.
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Landfill mining (LFM) is a strategy to mitigate environmental impacts associated with landfills, while simultaneously recovering dormant materials, energy carriers, and land resources. Although several case study assessments on the economy of LFM exist, a broader understanding of the driving factors is still lacking. This study aims at identifying generically important factors for the economy of LFM in Europe and understanding their role in developing economically feasible projects in view of different site, project and system-level conditions. Therefore, a set-based modeling approach is used to establish a large number (531,441) of LFM scenarios, evaluate their economic performance in terms of net present value (NPV), and analyze the relationships between input factors and economic outcome via global sensitivity analysis. The scenario results range from -139 Euro to +127 Euro/Mg of excavated waste, with 80% of the scenarios having negative NPVs. Variations in the costs for waste treatment and disposal and the avoided cost of alternative landfill management (i.e. if the landfill was not mined) have the strongest effect on the scenario NPVs, which illustrates the critical role of system level factors for LFM economy and the potential of policy intervention to incentivize LFM. Consequently, system conditions should guide site selection and project development, which is exemplified in the study for two extreme regional archetypes in terms of income and waste management standard. Future work should further explore the developed model to provide decision support on LFM strategies in consideration of alternative purposes, stakeholders, and objectives.
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Refuse Disposal , Waste Management , Costs and Cost Analysis , Europe , Mining , Waste Disposal FacilitiesABSTRACT
OBJECTIVE: The aim of this study was to determine the occurrence of latent tuberculosis infections (LTBI) and active TB in a cohort of patients with inflammatory bowel disease (IBD) treated with biologics. We also examined the effects of immunosuppressive drugs on indeterminate interferon-gamma release assays (IGRA) in LTBI screening. DESIGN: Retrospective study of patients treated with biologics between March 2007 and November 2015. SETTING: St Mark's Hospital, North West London, UK. PATIENTS: 732 patients with IBD who were screened for LTBI using either tuberculin skin test or IGRA before starting a biologic treatment. METHODS: Retrospective case note review of all patients with IBD who were screened for LTBI prior to initiating biologics. Patients who developed active TB were identified from the London TB register. RESULTS: Of 732 patients with IBD, 31 (4.2%) were diagnosed with and treated for LTBI with no significant side effects. Six of 596 patients (1.0%) who received biologic treatment developed active TB. There was a higher proportion of indeterminate IGRA in the immunosuppressive medication group compared with the non-immunosuppressive group (33% (59/181) compared with 9% (6/66), p<0.001). The combination of steroids and thiopurines had the highest proportion of indeterminate IGRA (64%, 16/25). High and low doses of steroids were equally likely to result in an indeterminate IGRA result (67% (8/12) and 57% (4/7), respectively). CONCLUSIONS: This study highlights the challenges of LTBI screening prior to commencing biologic therapy and demonstrates the risk of TB in patients who have been screened and who are receiving prolonged and continuing doses of antitumour necrosis factor.
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INTRODUCTION: Here we present a case of atraumatic splenic rupture secondary to varicella infection requiring emergency splenectomy. The presentation was as would be expected for epstein barr virus (EBV) related splenic injury, which is well documented in the literature. Dermatological findings however suggested varicella zoster, and viral serology subsequently confirmed the diagnosis. PRESENTATION OF CASE: A young Romanian male presented to the emergency department with peritonism without preceding trauma. Free fluid on USS was aspirated as frank blood and cross-sectional imaging demonstrated a ruptured spleen. He underwent emergency splenectomy and recovered well. During his presentation he was noted to have an erythematous rash with different rates of evolution raising the suspicion for Varicella Zoster. This was subsequently confirmed on viral serology. DISCUSSION: A number of precedents have been identified for spontaneous splenic rupture, however Varicella Zoster has only been reported a handful of times. A number of surgical options are available for splenic rupture, and guidelines exist for traumatic splenic injury. There is limited guidance on the most effective surgical management for spontaneous splenic ruptures with haemodyamic compromise. CONCLUSION: Atraumatic splenic rupture should be considered as an important differential in those presenting with abdominal pain and peritonism without a history of preceding trauma. Haematological and infectious diagnoses should be sought to identify causation for the splenic rupture.
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2016 TB National Institute for Health and Care Excellence (NICE) guidelines imply that contacts of extrapulmonary TB do not require screening for latent TB infection. At our high TB prevalence site, we identified 189 active cases of TB for whom there were 698 close contacts. 29.1% of the contacts of pulmonary TB and 10.7% of the contacts of extrapulmonary TB had active or latent TB infection. This supports screening contacts of extrapulmonary TB at our site and presents a way to access high-risk individuals. We propose to continue to screen the contacts of our patients with extrapulmonary TB and recommend other TB units audit their local results.
Subject(s)
Contact Tracing/methods , Mass Screening/methods , Tuberculosis/diagnosis , Adult , Humans , Middle Aged , Prevalence , Tuberculosis/epidemiology , United Kingdom/epidemiologyABSTRACT
BACKGROUND: Untreated, miliary tuberculosis (TB) has a mortality approaching 100%. As it is uncommon there is little specific data to guide its management. We report detailed data from a UK cohort of patients with miliary tuberculosis and the associations and predictive ability of admission blood tests with clinical outcomes. METHODS: Routinely collected demographic, clinical, blood, imaging, histopathological and microbiological data were assessed for all patients with miliary TB identified from the London TB register from 2008 to 2012 from Northwest London Hospitals NHS Trust. Multivariable logistic regression was used to assess factors independently associated with the need for critical care intervention. Receiver operator characteristics (ROC) were calculated to assess the discriminatory ability of admission blood tests to predict clinical outcomes. RESULTS: Fifty-two patients were identified with miliary tuberculosis, of whom 29% had confirmed central nervous system (CNS) involvement. Magnetic resonance imaging (MRI) was more sensitive than computed tomography (CT) or lumbar puncture for detecting CNS disease. Severe complications were frequent, with 15% requiring critical care intervention with mechanical ventilation. This was independently associated with admission hyponatraemia and elevated alanine aminotransferase (ALT). Having an admission sodium ≥125 mmol/L and an ALT <180 IU/L had 82% sensitivity and 100% specificity for predicting a favourable outcome with an area under the ROC curve (AUC) of 0.91. Despite the frequency of severe complications, one-year mortality was low at 2%. CONCLUSIONS: Although severe complications of miliary tuberculosis were frequent, mortality was low with timely access to critical care intervention, anti-tuberculous therapy and possibly corticosteroid use. Clinical outcomes could accurately be predicted using routinely collected biochemistry data.
Subject(s)
Central Nervous System Diseases/mortality , Tuberculosis, Miliary/complications , Tuberculosis, Miliary/mortality , Adolescent , Adult , Aged , Alanine Transaminase/blood , Biomarkers/analysis , Central Nervous System Diseases/diagnostic imaging , Central Nervous System Diseases/etiology , Central Nervous System Diseases/therapy , Child , Cohort Studies , Female , Humans , London/epidemiology , Magnetic Resonance Imaging , Male , Middle Aged , Respiration, Artificial , Tomography, X-Ray Computed , Tuberculosis, Miliary/therapy , Young AdultABSTRACT
BACKGROUND: We describe drug-induced liver injury (DILI) secondary to antituberculous treatment (ATT) in a large tuberculosis (TB) centre in London; we identify the proportion who had risk factors for DILI and the timing and outcome of DILI. METHODS: We identified consecutive patients who developed DILI whilst on treatment for active TB; patients with active TB without DILI were selected as controls. Comprehensive demographic and clinical data, management and outcome were recorded. RESULTS: There were 105 (6.9%) cases of ATT-associated DILI amongst 1529 patients diagnosed with active TB between April 2010 and May 2014. Risk factors for DILI were: low patient weight, HIV-1 co-infection, higher baseline ALP, and alcohol intake. Only 25.7% of patients had British or American Thoracic Society defined criteria for liver test (LT) monitoring. Half (53%) of the cases occurred within 2 weeks of starting ATT and 87.6% occurred within 8 weeks. Five (4.8%) of seven deaths were attributable to DILI. CONCLUSIONS: Only a quarter of patients who developed DILI had British or American Thoracic Society defined criteria for pre-emptive LT monitoring, suggesting that all patients on ATT should be considered for universal liver monitoring particularly during the first 8 weeks of treatment.
Subject(s)
Antitubercular Agents , Chemical and Drug Induced Liver Injury , Tuberculosis , Adolescent , Adult , Antitubercular Agents/adverse effects , Antitubercular Agents/therapeutic use , Chemical and Drug Induced Liver Injury/epidemiology , Chemical and Drug Induced Liver Injury/etiology , Female , Humans , London/epidemiology , Male , Middle Aged , Retrospective Studies , Tuberculosis/complications , Tuberculosis/drug therapy , Tuberculosis/epidemiology , United Kingdom , Young AdultABSTRACT
Rapidly progressive encephalopathy in an HIV-positive patient presents a major diagnostic and management challenge. CD8+ encephalitis is a severe but treatable form of HIV-related acute encephalopathy, characterised by diffuse perivascular and intraparenchymal CD8+ lymphocytic infiltration. It can occur in patients who are apparently stable on antiretroviral treatment and probably results from viral escape into the central nervous system. Treatment, including high-dose corticosteroids, can give an excellent neurological outcome, even in people with severe encephalopathy and a very poor initial neurological status. We report a woman with CD8+ encephalitis, with a normal CD4 count and undetectable serum viral load, who made a good recovery despite the severity of her presentation.
Subject(s)
AIDS Dementia Complex/drug therapy , AIDS Dementia Complex/immunology , Anti-Inflammatory Agents/therapeutic use , Anti-Retroviral Agents/therapeutic use , CD8-Positive T-Lymphocytes/pathology , AIDS Dementia Complex/pathology , Acute Disease , Adrenal Cortex Hormones/therapeutic use , CD8-Positive T-Lymphocytes/immunology , Female , Humans , Middle AgedABSTRACT
BACKGROUND: Clinical, radiological and microbiological criteria inform diagnosis of pulmonary Non-Tuberculous Mycobacteria (NTM) disease and treatment decisions. This multicentre, review aims to characterise NTM disease meeting ATS/IDSA criteria and define factors associated with initiation of treatment. METHODS: Sputum samples growing NTM from 5 London hospitals between 2010 and 2014 were identified. Data for HIV-negative individuals meeting ATS/IDSA guidelines for pulmonary NTM disease were extracted. Associations between clinical variables and treatment decision were investigated using Chi-squared, Fishers-exact or Mann Whitney tests. Factors associated with treatment in univariate analysis (p < 0.150) were included in a multivariate logistic regression model. RESULTS: NTM were identified from 817 individuals' sputum samples. 108 met ATS/IDSA criteria. 42/108 (39%) were initiated on treatment. Median age was 68 (56-78) in the cohort. On multivariate analysis, factors significantly associated with treatment of pulmonary NTM infection were: Cavitation on HRCT (OR: 6.49; 95% CI: 2.36-17.81), presenting with night sweats (OR 4.18; 95% CI: 1.08-16.13), and presenting with weight loss (OR 3.02; 95% CI: 1.15-7.93). Of those treated, 18(43%) have completed treatment, 9(21%) remain on treatment, 10(24%) stopped due to side effects, 5(12%) died during treatment. Mortality was 31% (n = 13) in treated versus 21% (n = 14) in the non-treated cohort. Subgroup analysis of individual NTM species did not observe any differences in treatment initiation or outcomes between groups. DISCUSSION: Decision to treat pulmonary NTM infection requires clinical judgement when interpreting clinical guidelines. Factors independently associated with decision to treat in this HIV-negative cohort include cavitation on HRCT and presenting with night sweats or weight loss.