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Causes and consequences of diagnostic delay in Guillain-Barré syndrome in a UK tertiary center.
No full textINTRODUCTION/AIMS
Understanding the potential causes and consequences of diagnostic delay in Guillain-Barré syndrome (GBS) could improve quality of care and outcomes. We aimed to determine these causes and consequences in our cohort of patients with GBS.
METHODS
We retrospectively reviewed records of subjects with GBS, admitted to our center at University Hospitals Birmingham, UK, between January 2005 and December 2020. We evaluated time to diagnosis from presentation, factors associated with diagnostic delay, and its potential consequences.
RESULTS
We included 119 consecutive subjects. Diagnostic delay at least 5 days from first presentation occurred in 27 of 119 (22.7%) of patients. Diagnostic delay was associated with age >60 years (odds ratio [OR], 3.58; 95% confidence interval [CI], 1.44-8.85), pre-existing cardiac/respiratory disease (OR, 4.10; 95% CI, 1.46-11.54), pre-existing diabetes (OR, 10.38; 95% CI, 2.47-43.69), documented normal initial neurological examination (OR, 2.49; 95% CI, 1.03-6.02), initial assessment by primary care (OR, 3.33; 95% CI, 1.22-9.10) and at least one visit for medical attention (OR, 10.29; 95% CI, 3.81-27.77). Diagnostic delay was not associated with length of inpatient stay, intensive care unit admission, ventilation, ability to walk at discharge, or inpatient mortality. Independent associations with diagnostic delay were observed for at least one visit for medical attention (OR, 10.15; 95% CI, 3.64-28.32) and pre-existing cardiac/respiratory disease (OR, 3.98; 95% CI, 1.19-13.28). An association of diagnostic delay with inpatient mortality was ascertained specifically in subjects with classic GBS (OR, 5.33; 95% CI, 1.1-25.87).
DISCUSSION
Diagnostic delay in GBS results from patient-specific factors and patient pathways. A high index of suspicion is appropriate for certain patient groups. Prospective studies are needed to further investigate this topic
The natural history of advanced chronic liver disease defined by transient elastography.
No full textBACKGROUND AND AIMS
The clinical course of cirrhosis does not follow a predictable trajectory. Transient elastography (TE) is commonly used in clinical practice to diagnose liver fibrosis and increasingly to risk stratify patients. The aim of this study was to assess the natural history of advanced chronic liver disease (ACLD) defined by TE using electronic health record (EHR) data in a multistate framework.
METHODS
TE data was collected between 2008 and 2019. Patients with a liver stiffness measurement (LSM) of >10kPa were included. Disease and procedure code information held in EHR was analysed. Clinical events including decompensation, hepatocellular carcinoma, and death were identified. Outcomes were described in a multistate model using flexible parametric survival methods including LSM and the albumin bilirubin (ALBI) score.
RESULTS
3028 patients were included. Median follow up was 3.1 years. LSM and ALBI were associated with the development of varices and decompensation, and ALBI, age, sex, and viral liver disease were associated with the development of hepatocellular carcinoma from the compensated state. The cumulative incidence of HCC before decompensation was low for patients with alcohol related liver disease (3.8%) and nonalcoholic fatty liver disease (1.3%) at five years after TE. Importantly, death was predicted to occur before decompensation or HCC in most cases.
CONCLUSIONS
Liver stiffness, ALBI score, and disease aetiology are each associated with outcomes in a large contemporary cohort with ACLD. EHR data can be used to define clinical progression in these patients, facilitating large clinical effectiveness trials and cost-effectiveness analyses
Acute Myocarditis Secondary to Paediatric Inflammatory Multisystem Syndrome Temporally Associated With COVID-19 Infection.
No full textA 17-year-old female, who was previously fit and well with no preexisting health conditions, presented with a four-day history of worsening shortness of breath and diarrhoea. She had recent close contact with a relative diagnosed with COVID-19. On clinical examination, she was drowsy, hypotensive, tachycardic, tachypnoeic, and pyrexial. Her blood tests showed elevated inflammatory markers and lymphopenia. She underwent a transthoracic echocardiogram, which confirmed a severely impaired left ventricular (LV) systolic function with an ejection fraction of 35%. An initial impression of acute viral myocarditis was made. Three separate polymerase chain reaction (PCR) tests for SARS-CoV-2 RNA were performed, but they all returned negative. The patient was not responding to initial therapy. Therefore, the regional paediatrics hospital was consulted, and a diagnosis of paediatric inflammatory multisystem syndrome temporally associated with COVID-19 (PIMS-TS) was made, based on similar regional presentations. The patient was administered IV immunoglobulin therapy, to which she responded very well. Following a five-day hospital stay, the patient was discharged home as medically stable. A repeat transthoracic echocardiogram (TTE) showed recovery of the LV systolic function to 62%. Few cases have been reported on myocardial involvement in young patients with PIMS-TS. This case report highlights the initial presentation, medical care, and clinical course of this patient
Unresected screen-detected ductal carcinoma in situ: Outcomes of 311 women in the Forget-Me-Not 2 study.
No full textBACKGROUND AND AIM
The natural history of ductal carcinoma in situ (DCIS) is poorly understood. The aim of this cohort study was to determine the outcomes of women who had no surgery for screen-detected DCIS in the 6 months following diagnosis.
METHODS
English breast screening databases were retrospectively searched for women diagnosed with DCIS without invasive cancer at screening and who had no record of surgery within 6 months of diagnosis. These were cross-referenced with cancer registry data. Details of the potentially eligible women were sent to the relevant breast screening units for verification and for completion of data forms detailing clinical, radiological and pathological findings, non-surgical treatment and subsequent clinical course.
RESULTS
Data for 311 eligible women (median age 62 years) were available. 60 women developed invasive cancer, 56 ipsilateral and 4 contralateral. Ipsilateral invasion risk increased approximately linearly with time for at least 10 years. The 10-year cumulative risk of ipsilateral invasion was 9% (95% CI 4-21%), 39% (24-58%) and 36% (24-50%) for low, intermediate and high grade DCIS respectively and was higher in younger women, in those with larger DCIS lesions and in those with microinvasion. Most invasive cancers that developed were grade 2 or 3.
CONCLUSION
The findings suggest that active surveillance may be a reasonable alternative to surgery in patients with low grade DCIS but that women with intermediate or high grade disease should continue to be offered surgery. This highlights the importance of reproducible grading of DCIS to ensure patients receive appropriate treatment
Compassionate End-of-Life Care in the Intensive Care Unit Involves Early Establishment of Treatment Goals.
No full textUK clinical guideline for the prevention and treatment of osteoporosis.
No full textThe National Osteoporosis Guideline Group (NOGG) has revised the UK guideline for the assessment and management of osteoporosis and the prevention of fragility fractures in postmenopausal women, and men age 50 years and older. Accredited by NICE, this guideline is relevant for all healthcare professionals involved in osteoporosis management.
INTRODUCTION
The UK National Osteoporosis Guideline Group (NOGG) first produced a guideline on the prevention and treatment of osteoporosis in 2008, with updates in 2013 and 2017. This paper presents a major update of the guideline, the scope of which is to review the assessment and management of osteoporosis and the prevention of fragility fractures in postmenopausal women, and men age 50 years and older.
METHODS
Where available, systematic reviews, meta-analyses and randomised controlled trials were used to provide the evidence base. Conclusions and recommendations were systematically graded according to the strength of the available evidence.
RESULTS
Review of the evidence and recommendations are provided for the diagnosis of osteoporosis, fracture-risk assessment and intervention thresholds, management of vertebral fractures, non-pharmacological and pharmacological treatments, including duration and monitoring of anti-resorptive therapy, glucocorticoid-induced osteoporosis, and models of care for fracture prevention. Recommendations are made for training; service leads and commissioners of healthcare; and for review criteria for audit and quality improvement.
CONCLUSION
The guideline, which has received accreditation from the National Institute of Health and Care Excellence (NICE), provides a comprehensive overview of the assessment and management of osteoporosis for all healthcare professionals involved in its management. This position paper has been endorsed by the International Osteoporosis Foundation and by the European Society for the Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases
Development and preliminary validation of the Sjögren's Tool for Assessing Response (STAR): a consensual composite score for assessing treatment effect in primary Sjögren's syndrome.
No full textOBJECTIVE
To develop a composite responder index in primary Sjögren's syndrome (pSS): the Sjögren's Tool for Assessing Response (STAR).
METHODS
To develop STAR, the NECESSITY (New clinical endpoints in primary Sjögren's syndrome: an interventional trial based on stratifying patients) consortium used data-driven methods based on nine randomised controlled trials (RCTs) and consensus techniques involving 78 experts and 20 patients. Based on reanalysis of rituximab trials and the literature, the Delphi panel identified a core set of domains with their respective outcome measures. STAR options combining these domains were proposed to the panel for selection and improvement. For each STAR option, sensitivity to change was estimated by the C-index in nine RCTs. Delphi rounds were run for selecting STAR. For the options remaining before the final vote, a meta-analysis of the RCTs was performed.
RESULTS
The Delphi panel identified five core domains (systemic activity, patient symptoms, lachrymal gland function, salivary gland function and biological parameters), and 227 STAR options combining these domains were selected to be tested for sensitivity to change. After two Delphi rounds, a meta-analysis of the 20 remaining options was performed. The candidate STAR was then selected by a final vote based on metrological properties and clinical relevance.
CONCLUSION
The candidate STAR is a composite responder index that includes all main disease features in a single tool and is designed for use as a primary endpoint in pSS RCTs. The rigorous and consensual development process ensures its face and content validity. The candidate STAR showed good sensitivity to change and will be prospectively validated by the NECESSITY consortium in a dedicated RCT
Associating transcriptomics data with inflammatory markers to understand tumour microenvironment in hepatocellular carcinoma.
No full textBACKGROUND
Liver cancer is the fourth leading cause of cancer-related death globally which is estimated to reach more than 1 million deaths a year by 2030. Among liver cancer types, hepatocellular carcinoma (HCC) accounts for approximately 90% of the cases and is known to have a tumour promoting inflammation regardless of its underlying aetiology. However, current promising treatment approaches, such as immunotherapy, are partially effective for most of the patients due to the immunosuppressive nature of the tumour microenvironment (TME). Therefore, there is an urgent need to fully understand TME in HCC and discover new immune markers to eliminate resistance to immunotherapy.
METHODS
We analyse three microarray datasets, using unsupervised and supervised methods, in an effort to discover signature genes. First, univariate, and multivariate, feature selection methods, such as the Boruta algorithm, are applied. Subsequently, an optimisation procedure, which utilises random forest algorithm with three dataset pairs combinations, is performed. The resulting optimal gene sets are then combined and further subjected to network analysis and pathway enrichment analysis so as to obtain information related to their biological relevance. The microarray datasets were analysed via the MCP-counter, CIBERSORT, TIMER, EPIC, and quanTIseq deconvolution methods and an estimation of cell type abundances for each dataset sample were identified. The differences in the cell type abundances, between the adjacent and tumour sample groups, were then assessed using a Wilcoxon Rank Sum test (p-value < 0.05).
RESULTS
The optimal gene signature sets, derived from each of the data pairs combination, achieved AUC values ranging from 0.959 to 0.988 in external validation sets using Random Forest model. CLEC1B and PTTG1 genes are retrieved across each optimal set. Among the signature genes, PTTG1, AURKA, and UBE2C genes are found to be involved in the regulation of mitotic sister chromatid separation and anaphase-promoting complex (APC) dependent catabolic process (adjusted p-value < 0.001). Additionally, the application of deconvolution algorithms revealed significant changes in cell type abundances of Regulatory T (Treg) cells, M0 and M1 macrophages, and T CD8 cells between adjacent and tumour samples.
CONCLUSION
We identified ECM1 gene as a potential immune-related marker acting through immune cell migration and macrophage polarisation. Our results indicate that macrophages, such as M0 macrophage and M1 macrophage cells, undergo significant changes in HCC TME. Moreover, our immune deconvolution approach revealed significant infiltration of Treg cells and M0 macrophages, and a significant decrease in T CD8 cells and M1 macrophages in tumour samples
Maresin 1 intervention Reverses Experimental Pulmonary Arterial Hypertension in mice.
No full textBACKGROUND AND PURPOSE
Pulmonary arterial hypertension (PAH) is a pulmonary vasculature obstructive disease that leads to right heart failure and death. Maresin 1 is an endogenous lipid mediator known to promote inflammation resolution. However, the effect of Maresin 1 on PAH remains unclear.
EXPERIMENTAL APPROACH
The serum Maresin 1 concentration was assessed using UPLC. A mouse model of PAH was established by combining the Sugen 5416 injection and hypoxia exposure (SuHx). After treatment with Maresin 1, the right ventricular systolic pressure (RVSP) and right ventricular function were measured by hemodynamic measurement and echocardiography, respectively. Vascular remodeling was evaluated by histological staining. Confocal and western blot were used to test related protein expression. In vitro, cell migration, proliferation and apoptosis assays were performed in primary rat pulmonary artery smooth muscle cells (PASMCs). Western blotting and siRNA transfection were used to clarify the mechanism of Maresin 1.
KEY RESULTS
Endogenous serum Maresin 1 was decreased in PAH patients and mice. Maresin 1 treatment decreased RVSP and attenuated the right ventricular dysfunction (RVD) in murine PAH model. Maresin 1 reversed abnormal changes in pulmonary vascular remodeling, attenuating endothelial to mesenchymal transformation (EndoMT) and enhancing apoptosis of α-SMA positive cells. Furthermore, Maresin 1 inhibited PASMC proliferation and promoted apoptosis by inhibiting STAT, AKT, ERK and FoxO1 phosphorylation via LGR6.
CONCLUSION AND IMPLICATIONS
Maresin 1 improved abnormal pulmonary vascular remodeling and right ventricular dysfunction in PAH mice, targeting aberrant PASMC proliferation. This suggests Maresin 1 may have a potent therapeutic effect in vascular disease
Effectiveness of interventions to reduce household air pollution from solid biomass fuels and improve maternal and child health outcomes in low- and middle-income countries: A systematic review and meta-analysis.
No full textInterventions to reduce household air pollution (HAP) are key to reducing associated morbidity and mortality in low- and middle- income countries (LMICs); especially among pregnant women and young children. This systematic review aims to determine the effectiveness of interventions aimed to reduce HAP exposure associated with domestic solid biomass fuel combustion, compared to usual cooking practices, for improving health outcomes in pregnant women and children under five in LMIC settings. A systematic review and meta-analysis was undertaken with searches undertaken in MEDLINE, EMBASE, CENTRAL, GIM, ClinicalTrials.gov, and Greenfile in August 2020. Inclusion criteria were experimental, non-experimental, or quasi-experimental studies investigating the impact of interventions to reduce HAP exposure and improve associated health outcomes among pregnant women or children under 5 years. Study selection, data extraction, and quality assessment using the Effective Public Health Practice Project tool were undertaken independently by two reviewers. Seventeen out of 7293 retrieved articles (seven pregnancy, nine child health outcome; 13 studies) met the inclusion criteria. These assessed improved cookstoves (ICS; n = 10 studies), ethanol stoves (n = 1 study), and Liquefied Petroleum Gas (LPG; n = 2 studies) stoves interventions. Meta-analysis showed no significant effect of ICS interventions compared to traditional cooking for risk of preterm birth (n = 2 studies), small for gestational age (n = 2 studies), and incidence of acute respiratory infections (n = 6 studies). Although an observed increase in mean birthweight was observed, this was not statistically significant (n = 4). However, ICS interventions reduced the incidence of childhood burns (n = 3; observations = 41 723; Rate Ratio: 0.66 [95% CI: 0.45-0.96]; I : 46.7%) and risk of low birth weight (LBW; n = 4; observations = 3456; Odds Ratio: 0.73 [95% CI: 0.61-0.87]; I : 21.1%). Although few studies reported health outcomes, the data indicate that ICS interventions were associated with reduced risk of childhood burns and LBW. The data highlight the need for the development and implementation of robust, well-reported and monitored, community-driven intervention trials with longer-term participant follow-up