A multidisciplinary evaluation of suspected, non-confirmed cases of COVID-19 including chest CT, as compared to World Health Organization recommendations.

AIM: To report an audit of the evaluation of suspected, unconfirmed cases of COVID-19 including chest computed tomography (CT), as compared to World Health Organization recommendations. METHODS: A clinical audit was undertaken examining the evaluation of patients with suspected COVID-19 with negative SARS-CoV-2 reverse transcriptase polymerase chain reaction (RT-PCR) results, with comparison to WHO recommendations. A retrospective chart review was undertaken for 90 patients examining investigations, in particular CT, used to clarify the diagnosis. RESULTS: Ninety patients underwent additional investigation. Seventy-five per cent adherence to WHO recommendations was observed. Fifty-two men (57.78%) and 38 (42.22%) women were investigated, with a median age of 69 years (range 20-96 years). Seventy-nine chest CT examinations demonstrated positive, indeterminate, and negative rates for COVID-19 of 3.79%, 24.1%, and 72.15% respectively. Three patients had discordant swab results with initially negative and subsequently positive results for SARS-CoV-2, resulting in false-negative rates of 5.1% for those retested. Combining discordant RT-PCR swab results, positive radiology, and patients treated as COVID-19-positive due to indeterminate radiology and highly consistent symptoms, resulted in a false-negative rate for initial SARS-CoV-2 RT-PCR swabs of 16.67%. CONCLUSION: Seventy-five per cent compliance with relevant WHO guidance and a false-negative rate for initial swabs of 16.67% was demonstrated. Further evidence is needed to fully determine the utility of chest CT in the diagnosis of COVID-19 in the context of initial false-negative RT-PCR results.

Longitudinal point prevalence survey of antibacterial use in Northern Ireland using the European Surveillance of Antimicrobial Consumption (ESAC) PPS and Global-PPS tool.

Antimicrobial resistance is a limiting factor for the success of the treatment of infectious diseases and is associated with increased morbidity and cost. The present study aims to evaluate prescribing patterns of antimicrobials and quantify progress in relation to targets for quality improvement in the prescription of antimicrobials in Northern Ireland's secondary care sector using three repetitive point prevalence surveys (PPS) over a 6-year period: the European Surveillance of Antimicrobial Consumption (ESAC-PPS) in 2009 and 2011 and the Global-PPS on Antimicrobial Consumption and Resistance in 2015. Out of 3605 patients surveyed over the three time points, 1239 (34.4%) were treated with an antibiotic, the most frequently prescribed antibiotic groups were a combination of penicillins, including ß-lactamase inhibitors. Compliance with hospital antibiotic policies in 2009, 2011 and 2015 were 54.5%, 71.5% and 79.9%, respectively. Likewise, an indication for treatment was recorded in patient notes 88.5%, 87.7% and 90.6% in 2009, 2011 and 2015, respectively, and surgical prophylactic antibiotic prescriptions for >24 h was 3.9%, 3.2% and 0.7% in 2009, 2011 and 2015, respectively. Treatment based on biomarker data was used in 61.5% of cases. In conclusion, a general trend in the improvement of key antimicrobial-related quality indicators was noted. The PPS tool provided a convenient, inexpensive surveillance system of antimicrobial consumption and should be considered an essential component to establish and maintain informed antibiotic stewardship in hospitals.

Treatable childhood neuronopathy caused by mutations in riboflavin transporter RFVT2.

Childhood onset motor neuron diseases or neuronopathies are a clinically heterogeneous group of disorders. A particularly severe subgroup first described in 1894, and subsequently called Brown-Vialetto-Van Laere syndrome, is characterized by progressive pontobulbar palsy, sensorineural hearing loss and respiratory insufficiency. There has been no treatment for this progressive neurodegenerative disorder, which leads to respiratory failure and usually death during childhood. We recently reported the identification of SLC52A2, encoding riboflavin transporter RFVT2, as a new causative gene for Brown-Vialetto-Van Laere syndrome. We used both exome and Sanger sequencing to identify SLC52A2 mutations in patients presenting with cranial neuropathies and sensorimotor neuropathy with or without respiratory insufficiency. We undertook clinical, neurophysiological and biochemical characterization of patients with mutations in SLC52A2, functionally analysed the most prevalent mutations and initiated a regimen of high-dose oral riboflavin. We identified 18 patients from 13 families with compound heterozygous or homozygous mutations in SLC52A2. Affected individuals share a core phenotype of rapidly progressive axonal sensorimotor neuropathy (manifesting with sensory ataxia, severe weakness of the upper limbs and axial muscles with distinctly preserved strength of the lower limbs), hearing loss, optic atrophy and respiratory insufficiency. We demonstrate that SLC52A2 mutations cause reduced riboflavin uptake and reduced riboflavin transporter protein expression, and we report the response to high-dose oral riboflavin therapy in patients with SLC52A2 mutations, including significant and sustained clinical and biochemical improvements in two patients and preliminary clinical response data in 13 patients with associated biochemical improvements in 10 patients. The clinical and biochemical responses of this SLC52A2-specific cohort suggest that riboflavin supplementation can ameliorate the progression of this neurodegenerative condition, particularly when initiated soon after the onset of symptoms.

Distinctive neurological phenotype associated with partial trisomy of chromosome 16.

We present a case of a live born female infant who presented in early life with a movement disorder, lack of developmental progress and neutropenia. Extensive neuro-metabolic investigation was non-diagnostic. Chromosome analysis of cultured lymphocyte cells showed an abnormal chromosome 16 with additional material noted in the proximal long arm. Additional fluorescence in situ hybridisation studies identified this additional material to represent a duplication of the long arm of chromosome 16 between 16q11.2 and 16q21. There was progressive decline and death by 10 months. Dystonia cortical blindness and neutropenia have not been a reported feature of trisomy 16 to date.

A national house-staff audit of medical prophylaxis in medical patients for the PREVENTion of Venous ThromboEmbolism (PREVENT-VTE).

We established a national audit to assess the thromboprophylaxis rate for venous thromoembolism (VTE) in at risk medical patients in acute hospitals in the Republic of Ireland and to determine whether the use of stickers to alert physicians regarding thromboprophylaxis would double the rate prophylaxis in a follow-up audit. 651 acute medical admission patients in the first audit and 524 in the second re-audit were recruited. The mean age was 66.5 yrs with similar numbers of male and female patients and 265 (22.6%) patients were active smokers. The first and second audits identified 549 (84%) and 487 (93%) of patients at-risk for VTE respectively. Of the at-risk patients, 163 (29.7%) and 132 (27.1%) received LMWH in the first and second audit respectively. Mechanical thromboprophylaxis was instigated in 75 (13.6%) patients in the first and 86 (17.7%) patients in the second audit. The placement of stickers in patient charts didn't produce a significant increase in the number of at risk patients treated in the second audit. There is unacceptably low adherence to the ACCP guidelines in Ireland and more complex intervention than chart reminders are required to improve compliance.

A point prevalence survey of antibiotic use in four acute-care teaching hospitals utilizing the European Surveillance of Antimicrobial Consumption (ESAC) audit tool.

The objective of this research was to assess current patterns of hospital antibiotic prescribing in Northern Ireland and to determine targets for improving the quality of antibiotic prescribing. A point prevalence survey was conducted in four acute teaching hospitals. The most commonly used antibiotics were combinations of penicillins including ß-lactamase inhibitors (33·6%), metronidazole (9·1%), and macrolides (8·1%). The indication for treatment was recorded in 84·3% of the prescribing episodes. A small fraction (3·9%) of the surgical prophylactic antibiotic prescriptions was for >24 h. The results showed that overall 52·4% of the prescribed antibiotics were in compliance with the hospital antibiotic guidelines. The findings identified the following indicators as targets for quality improvement: indication recorded in patient notes, the duration of surgical prophylaxis and compliance with hospital antibiotic guidelines. The results strongly suggest that antibiotic use could be improved by taking steps to address the identified targets for quality improvement.

Exercise as an end-point in pulmonary hypertension trials.

With recent advances in our understanding of pulmonary hypertension and with ever increasing therapeutic options at our disposal, it remains disappointing that clinical markers of disease progression remain dated. There has long been a search for a more robust clinical correlate than the 6 minute walk test. Resting right heart pressures do not increase linearly with worsening disease, limiting their use as primary endpoints. Some progress has been made however, with 'time to clinical worsening' a composite endpoint of several markers of disease severity. Trials have also been undertaken to evaluate the merits of echocardiographic indices, cardio pulmonary exercise testing and cardiac MRI, with mixed results. With the lack of a sensitive and specific biomarker for pulmonary hypertension, the goal of finding a reproducible endpoint that accurately reflects disease severity and prognosis remains elusive. In this article we discuss relevant endpoints and focus on exercise haemodynamics as a primary endpoint for clinical trials.

Progress in Arabidopsis genome sequencing and functional genomics.

Arabidopsis thaliana has a relatively small genome of approximately 130 Mb containing about 10% repetitive DNA. Genome sequencing studies reveal a gene-rich genome, predicted to contain approximately 25000 genes spaced on average every 4.5 kb. Between 10 to 20% of the predicted genes occur as clusters of related genes, indicating that local sequence duplication and subsequent divergence generates a significant proportion of gene families. In addition to gene families, repetitive sequences comprise individual and small clusters of two to three retroelements and other classes of smaller repeats. The clustering of highly repetitive elements is a striking feature of the A. thaliana genome emerging from sequence and other analyses.

Sequence and analysis of chromosome 4 of the plant Arabidopsis thaliana.

The higher plant Arabidopsis thaliana (Arabidopsis) is an important model for identifying plant genes and determining their function. To assist biological investigations and to define chromosome structure, a coordinated effort to sequence the Arabidopsis genome was initiated in late 1996. Here we report one of the first milestones of this project, the sequence of chromosome 4. Analysis of 17.38 megabases of unique sequence, representing about 17% of the genome, reveals 3,744 protein coding genes, 81 transfer RNAs and numerous repeat elements. Heterochromatic regions surrounding the putative centromere, which has not yet been completely sequenced, are characterized by an increased frequency of a variety of repeats, new repeats, reduced recombination, lowered gene density and lowered gene expression. Roughly 60% of the predicted protein-coding genes have been functionally characterized on the basis of their homology to known genes. Many genes encode predicted proteins that are homologous to human and Caenorhabditis elegans proteins.