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Can symptoms of anosmia and dysgeusia be diagnostic for COVID-19?
No full textOBJECTIVE
Olfactory and taste dysfunction (OTD) is a potential neurological manifestation of coronavirus-2019 (COVID-19). We aimed to investigate the diagnostic value of symptoms of anosmia and dysgeusia for COVID-19.
METHODS
A comprehensive electronic search was conducted using PubMed, MEDLINE, Scopus, Cochrane database, and Google Scholar from 1 June 2020 to 12 June 2020. All studies reporting symptoms of anosmia and dysgeusia in COVID-19-positive patients were included. A total of 23 studies were included in the systematic review.
RESULTS
Symptoms of anosmia and dysgeusia were frequently reported by COVID-19-positive patients. Symptoms were more common in females and in younger patients. There was no direct association between the severity of COVID-19 and the presence of symptoms. However, some evidence was found for a longer duration of these symptoms and increased severity of COVID-19 infection in young patients.
CONCLUSION
OTD is commonly reported by COVID-19 patients. Due to limited literature on the association between OTD and COVID-19, it is currently not possible to conclude that these symptoms alone can be used to diagnose COVID-19. However, the presence of OTD can potentially be used as a screening tool for COVID-19 especially in young and female patients. Further research is required to establish the true diagnostic value of these symptoms and efficacy as screening tools for COVID-19 patients
Peripheral nerve electrophysiology studies in relation to fatigue in patients with chronic inflammatory demyelinating polyneuropathy.
No full textOBJECTIVE
To explore the relationship between fatigue, standard electrophysiological parameters and number and size of functioning motor units in patients with chronic inflammatory demyelinating polyneuropathy (CIDP).
METHODS
Experienced fatigue was assessed using the linearly-weighted, modified Rasch-built fatigue severity scale (R-FSS) and the multidimensional Checklist of Individual Strength (CIS). Averaged electrophysiology values were calculated from multiple nerves. Motor Unit Number Index (MUNIX) technique was utilised to assess motor unit function. Assessments were repeated in 15 patients receiving regular intravenous immunoglobulin therapy, with changes in parameters calculated.
RESULTS
R-FSS and CIS scores did not correlate MUNIX or MUSIX sum scores from 3 different muscles. Inverse correlation was observed only between distal CMAP area and R-FSS but not CIS scores. However, changes in distal CMAP area and R-FSS scores on repeat assessment were not correlated.
CONCLUSIONS
Experienced fatigue does not appear to correlate with loss of functioning motor units in patients with CIDP. Changes in experienced fatigue on repeat assessment did not correlate with changes in any of the electrophysiological parameters, suggesting fatigue experienced in CIDP is not strongly correlated with peripheral nerve dysfunction.
SIGNIFICANCE
Nerve conduction studies and MUNIX values do not appear to be useful surrogate markers for fatigue in CIDP
Circulating tumour DNA analysis to direct therapy in advanced breast cancer (plasmaMATCH): a multicentre, multicohort, phase 2a, platform trial.
No full textBACKGROUND
Circulating tumour DNA (ctDNA) testing might provide a current assessment of the genomic profile of advanced cancer, without the need to repeat tumour biopsy. We aimed to assess the accuracy of ctDNA testing in advanced breast cancer and the ability of ctDNA testing to select patients for mutation-directed therapy.
METHODS
We did an open-label, multicohort, phase 2a, platform trial of ctDNA testing in 18 UK hospitals. Participants were women (aged ≥18 years) with histologically confirmed advanced breast cancer and an Eastern Cooperative Oncology Group performance status 0-2. Patients had completed at least one previous line of treatment for advanced breast cancer or relapsed within 12 months of neoadjuvant or adjuvant chemotherapy. Patients were recruited into four parallel treatment cohorts matched to mutations identified in ctDNA: cohort A comprised patients with ESR1 mutations (treated with intramuscular extended-dose fulvestrant 500 mg); cohort B comprised patients with HER2 mutations (treated with oral neratinib 240 mg, and if oestrogen receptor-positive with intramuscular standard-dose fulvestrant); cohort C comprised patients with AKT1 mutations and oestrogen receptor-positive cancer (treated with oral capivasertib 400 mg plus intramuscular standard-dose fulvestrant); and cohort D comprised patients with AKT1 mutations and oestrogen receptor-negative cancer or PTEN mutation (treated with oral capivasertib 480 mg). Each cohort had a primary endpoint of confirmed objective response rate. For cohort A, 13 or more responses among 78 evaluable patients were required to infer activity and three or more among 16 were required for cohorts B, C, and D. Recruitment to all cohorts is complete and long-term follow-up is ongoing. This trial is registered with ClinicalTrials.gov, NCT03182634; the European Clinical Trials database, EudraCT2015-003735-36; and the ISRCTN registry, ISRCTN16945804.
FINDINGS
Between Dec 21, 2016, and April 26, 2019, 1051 patients registered for the study, with ctDNA results available for 1034 patients. Agreement between ctDNA digital PCR and targeted sequencing was 96-99% (n=800, kappa 0·89-0·93). Sensitivity of digital PCR ctDNA testing for mutations identified in tissue sequencing was 93% (95% CI 83-98) overall and 98% (87-100) with contemporaneous biopsies. In all cohorts, combined median follow-up was 14·4 months (IQR 7·0-23·7). Cohorts B and C met or exceeded the target number of responses, with five (25% [95% CI 9-49]) of 20 patients in cohort B and four (22% [6-48]) of 18 patients in cohort C having a response. Cohorts A and D did not reach the target number of responses, with six (8% [95% CI 3-17]) of 74 in cohort A and two (11% [1-33]) of 19 patients in cohort D having a response. The most common grade 3-4 adverse events were raised gamma-glutamyltransferase (13 [16%] of 80 patients; cohort A); diarrhoea (four [25%] of 20; cohort B); fatigue (four [22%] of 18; cohort C); and rash (five [26%] of 19; cohort D). 17 serious adverse reactions occurred in 11 patients, and there was one treatment-related death caused by grade 4 dyspnoea (in cohort C).
INTERPRETATION
ctDNA testing offers accurate, rapid genotyping that enables the selection of mutation-directed therapies for patients with breast cancer, with sufficient clinical validity for adoption into routine clinical practice. Our results demonstrate clinically relevant activity of targeted therapies against rare HER2 and AKT1 mutations, confirming these mutations could be targetable for breast cancer treatment.
FUNDING
Cancer Research UK, AstraZeneca, and Puma Biotechnology
Rehabilitation Levels in COVID-19 Patients Admitted to Intensive Care Requiring Invasive Ventilation: An Observational Study.
No full textRATIONALE
Patients with severe COVID-19 have complex organ support needs that necessitate prolonged stays in the intensive care, likely to result in a high incidence of neuromuscular weakness and loss of well being. Early and structured rehabilitation has been associated with improved outcomes for patients requiring prolonged periods of mechanical ventilation, but at present no data are available to describe similar interventions or outcomes in COVID-19 populations.
OBJECTIVES
To describe the demographics, clinical status, level of rehabilitation and mobility status at ICU discharge of patients with COVID-19.
METHODS
Adults admitted to ICU with a confirmed diagnosis of COVID-19 and mechanically ventilated for >24 hours were included. Rehabilitation status was measured daily using the Manchester Mobility Score (MMS) to identify the time taken to first mobilise (defined as sitting on the edge of the bed or higher) and highest level of mobility achieved at ICU discharge.
RESULTS
A total of n=177 patients were identified, of whom n=110 survived to ICU discharge and were included in the subsequent analysis. Whilst on ICU, patients required prolonged periods of mechanical ventilation (mean 19 ± 10 days), most received neuromuscular blockade (90%) and 67% were placed in the prone position on at least one occasion. The mean ± SD time to first mobilise was 14 ± 7 days, with a median MMS at ICU discharge of 5 (interquartile range: 4-6), which represents participants able to stand and step round to a chair with or without assistance. Time to mobilise was significantly longer in those with higher BMI (p<0.001), whilst older patients (p=0.012) and those with more comorbidities (p=0.017) were more likely to require further rehabilitation post-discharge.
CONCLUSION
The early experience of the COVID-19 pandemic in the UK resembles the experience in other countries, with high acuity of illness and prolonged period of mechanical ventilation required for those patients admitted to ICU. Whilst the time to commence rehabilitation was delayed due to this severity of illness, rehabilitation was possible within the ICU, and led to increased levels of mobility from waking prior to ICU discharge. Clinical trial registered with ClinicalTrials.gov (NCT04396197)
Peripheral arterial disease in patients with atrial fibrillation: The Atrial Fibrillation Follow-Up Investigation of Rhythm Management (AFFIRM) study.
No full textBACKGROUND
Peripheral arterial disease has been linked with worse outcomes in patients with atrial fibrillation. The aim of this study is to assess the impact of peripheral arterial disease on mortality and stroke in a cohort of atrial fibrillation patients.
METHODS
This was an ancillary analysis of the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) trial. A comparison of baseline characteristics was made between atrial fibrillation patients with and without diagnosed peripheral arterial disease. Multivariate cox regression analysis was performed to compare the risk of stroke, death and cardiovascular death among the two groups.
RESULTS
The prevalence of peripheral arterial disease in the whole cohort of 4060 atrial fibrillation patients was 6.7%. Patients with peripheral arterial disease tended to be older, had higher prevalence of diabetes mellitus, hypertension and smoking, they were more likely to give a history of coronary artery disease, heart failure, cardiac surgery or cardiac intervention and stroke or TIA (all p<0.05). After multivariate adjustment, peripheral arterial disease was significantly associated with overall higher mortality (HR: 1.34, 95%CI 1.06- 1.70, p= 0.016) in atrial fibrillation patients, but the rates of ischaemic stroke were similar in the two groups (3.9% vs 3.5%, p= 0.874). Subgroup analysis confined to the non-anticoagulated atrial fibrillation patients showed that peripheral arterial disease was an independent predictor of ischaemic stroke (HR: 3.37, 95%CI 1.25- 9.09, p< 0.016).
CONCLUSION
Peripheral arterial disease predicts higher mortality in atrial fibrillation, and was an independent predictor of ischaemic stroke in non-anticoagulated atrial fibrillation patients. Proactive surveillance and optimization of medical management in this group of patients is warranted, given the high risks associated with peripheral arterial disease where atrial fibrillation is also present
A phase 2 randomized, double-blind, placebo-controlled, proof-of-concept study of oral seletalisib in primary Sjögren's syndrome.
No full textOBJECTIVES
This phase 2 proof-of-concept study (NCT02610543) assessed efficacy, safety and effects on salivary gland inflammation of seletalisib, a potent and selective PI3Kδ inhibitor, in patients with moderate-to-severe primary Sjögren's syndrome (PSS).
METHODS
Adults with PSS were randomized 1:1 to seletalisib 45 mg/day or placebo, in addition to current PSS therapy. Primary end points were safety and tolerability and change from baseline in EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) score at week 12. Secondary end points included change from baseline at week 12 in EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) score and histological features in salivary gland biopsies.
RESULTS
Twenty-seven patients were randomized (seletalisib n = 13, placebo n = 14); 20 completed the study. Enrolment challenges led to early study termination with loss of statistical power (36% vs 80% planned). Nonetheless, a trend for improvement in ESSDAI and ESSPRI [difference vs placebo: -2.59 (95% CI: -7.30, 2.11; P=0.266) and -1.55 (95% CI: -3.39, 0.28), respectively] was observed at week 12. No significant changes were seen in saliva and tear flow. Serious adverse events (AEs) were reported in 3/13 of patients receiving seletalisib vs 1/14 for placebo and 5/13 vs 1/14 discontinued due to AEs, respectively. Serum IgM and IgG concentrations decreased in the seletalisib group vs placebo. Seletalisib demonstrated efficacy in reducing size and organisation of salivary gland inflammatory foci and in target engagement, thus reducing PI3K-mTOR signalling compared with placebo.
CONCLUSION
Despite enrolment challenges, seletalisib demonstrated a trend towards clinical improvement in patients with PSS. Histological analyses demonstrated encouraging effects of seletalisib on salivary gland inflammation and organisation.
TRIAL REGISTRATION
https://clinicaltrials.gov, NCT02610543
Tortuous internal carotid artery: an important differential of the pulsatile oropharyngeal mass.
No full textInitial hospital preparation and response to fight the COVID-19 pandemic, based on the British university hospital experience.
No full textImaging based uveitis surveillance in juvenile idiopathic arthritis: feasibility, acceptability and diagnostic performance.
No full textOBJECTIVE
Children with juvenile idiopathic arthritis need regular examinations for uveitis to avoid visual morbidity from the most common extra-articular manifestation of disease. We investigated the feasibility, acceptability and performance of optical coherence tomography (OCT) imaging based diagnosis of uveitis.
METHODS
Observational cross-sectional study involving children with and without uveitis. Children underwent routine clinical examination and acquisition of anterior segment (AS) OCT scans images of intraocular inflammatory cells. Acceptability of image acquisition was assessed using a visual analogue scale, and duration of image acquisition. Inter and intra-observer variability of manual counting of acquired images (Bland-Altman limits of agreement), correlation between imaging and routine assessment, and sensitivity and specificity of AS-OCT detection of active inflammation were assessed.
RESULTS
Of 26 children aged 3yrs to 15yrs (median 8yrs) who underwent imaging, 12 had active inflammation. All patients rated acceptability of image acquisition as at least 8·5/10. Time taken to acquire images ranged from 1·5mins to 22mins (median 8mins). There was good positive correlation between clinical assessment and image based cell quantification (R =0·63, p=0·002). Sensitivity of AS-OCT manual image cell count for diagnosis of active inflammation was 92% (95% Confidence interval 62%-99%), specificity 86% (58%-98%), and negative predictive value ('ruling-out' uveitis) 92% (65%-99%).
CONCLUSION
Non-contact, high-resolution imaging for JIA uveitis surveillance is feasible, acceptable to patients, and holds the promise of transforming paediatric practice. Further work is needed to determine the analytic and clinical validity of AS-OCT quantification of active inflammation, and the clinical and cost-effectiveness of imaging based disease monitoring
