COVID-19: a retrospective cohort study with focus on the over-80s and hospital-onset disease.

BACKGROUND: Data from the UK COVID-19 outbreak are emerging, and there are ongoing concerns about a disproportionate effect on ethnic minorities. There is very limited information on COVID-19 in the over-80s, and the rates of hospital-onset infections are unknown. METHODS: This was a retrospective cohort study from electronic case records of the first 450 patients admitted to our hospital with PCR-confirmed COVID-19, 77% of the total inpatient caseload to date. Demographic, clinical and biochemical data were extracted. The primary endpoint was death during the index hospital admission. The characteristics of all patients, those over 80 years of age and those with hospital-onset COVID-19 were examined. RESULTS: The median (IQR) age was 72 (56, 83), with 150 (33%) over 80 years old and 60% male. Presenting clinical and biochemical features were consistent with those reported elsewhere. The ethnic breakdown of patients admitted was similar to that of our underlying local population. Inpatient mortality was high at 38%. Patients over 80 presented earlier in their disease course and were significantly less likely to present with the typical features of cough, breathlessness and fever. Cardiac co-morbidity and markers of cardiac dysfunction were more common, but not those of bacterial infection. Mortality was significantly higher in this group (60% vs 28%, p < 0.001). Thirty-one (7%) patients acquired COVID-19 having continuously been in hospital for a median of 20 (14, 36) days. The peak of hospital-onset infections occurred at the same time as the overall peak of admitted infections. Despite being older and more frail than those with community-onset infection, their outcomes were no worse. CONCLUSIONS: Inpatient mortality was high, especially among the over-80s, who are more likely to present atypically. The ethnic composition of our caseload was similar to the underlying population. While a significant number of patients acquired COVID-19 while already in hospital, their outcomes were no worse.

Fluoroquinolones and isoniazid-resistant tuberculosis: implications for the 2018 WHO guidance.

INTRODUCTION: 2018 World Health Organization (WHO) guidelines for the treatment of isoniazid (H)-resistant (Hr) tuberculosis recommend a four-drug regimen: rifampicin (R), ethambutol (E), pyrazinamide (Z) and levofloxacin (Lfx), with or without H ([H]RZE-Lfx). This is used once Hr is known, such that patients complete 6 months of Lfx (≥6[H]RZE-6Lfx). This cohort study assessed the impact of fluoroquinolones (Fq) on treatment effectiveness, accounting for Hr mutations and degree of phenotypic resistance. METHODS: This was a retrospective cohort study of 626 Hr tuberculosis patients notified in London, 2009-2013. Regimens were described and logistic regression undertaken of the association between regimen and negative regimen-specific outcomes (broadly, death due to tuberculosis, treatment failure or disease recurrence). RESULTS: Of 594 individuals with regimen information, 330 (55.6%) were treated with (H)RfZE (Rf=rifamycins) and 211 (35.5%) with (H)RfZE-Fq. The median overall treatment period was 11.9 months and median Z duration 2.1 months. In a univariable logistic regression model comparing (H)RfZE with and without Fqs, there was no difference in the odds of a negative regimen-specific outcome (baseline (H)RfZE, cluster-specific odds ratio 1.05 (95% CI 0.60-1.82), p=0.87; cluster NHS trust). Results varied minimally in a multivariable model. This odds ratio dropped (0.57, 95% CI 0.14-2.28) when Hr genotype was included, but this analysis lacked power (p=0.42). CONCLUSIONS: In a high-income setting, we found a 12-month (H)RfZE regimen with a short Z duration to be similarly effective for Hr tuberculosis with or without a Fq. This regimen may result in fewer adverse events than the WHO recommendations.

Direct Whole-Genome Sequencing of Sputum Accurately Identifies Drug-Resistant Mycobacterium tuberculosis Faster than MGIT Culture Sequencing.

The current methods available to diagnose antimicrobial-resistant Mycobacterium tuberculosis infections require a positive culture or only test a limited number of resistance-associated mutations. A rapid accurate identification of antimicrobial resistance enables the prompt initiation of effective treatment. Here, we determine the utility of whole-genome sequencing (WGS) of M. tuberculosis directly from routinely obtained diagnostic sputum samples to provide a comprehensive resistance profile compared to that from mycobacterial growth indicator tube (MGIT) WGS. We sequenced M. tuberculosis from 43 sputum samples by targeted DNA enrichment using the Agilent SureSelectXT kit, and 43 MGIT positive samples from each participant. Thirty two (74%) sputum samples and 43 (100%) MGIT samples generated whole genomes. The times to antimicrobial resistance profiles and concordance were compared with Xpert MTB/RIF and phenotypic resistance testing from cultures of the same samples. Antibiotic susceptibility could be predicted from WGS of sputum within 5 days of sample receipt and up to 24 days earlier than WGS from MGIT culture and up to 31 days earlier than phenotypic testing. Direct sputum results could be reduced to 3 days with faster hybridization and if only regions encoding drug resistance are sequenced. We show that direct sputum sequencing has the potential to provide comprehensive resistance detection significantly faster than MGIT whole-genome sequencing or phenotypic testing of resistance from cultures in a clinical setting. This improved turnaround time enables prompt appropriate treatment with associated patient and health service benefits. Improvements in sample preparation are necessary to ensure comparable sensitivities and complete resistance profile predictions in all cases.

Variation in C - reactive protein response according to host and mycobacterial characteristics in active tuberculosis.

BACKGROUND: The C - reactive protein (CRP) response is often measured in patients with active tuberculosis (TB) yet little is known about its relationship to clinical features in TB, or whether responses differ between ethnic groups or with different Mycobacterium tuberculosis (M.tb) strain types. We report the relationship between baseline serum CRP prior to treatment and disease characteristics in a metropolitan population with TB resident in a low TB incidence region. METHODS: People treated for TB at four London, UK sites between 2003 and 2014 were assessed and data collected on the following characteristics: baseline CRP level; demographics (ethnicity, gender and age); HIV status; site of TB disease; sputum smear (in pulmonary cases) and culture results. The effect of TB strain-type was also assessed in culture-positive pulmonary cases using VNTR typing data. RESULTS: Three thousands two hundred twenty-two patients were included in the analysis of which 72 % had a baseline CRP at or within 4 weeks prior to starting TB treatment. CRP results were significantly higher in culture positive cases compared to culture negative cases: median 49 mg/L (16-103 mg/L) vs 19 mg/L (IQR 5-72 mg/L), p = <0.001. In those with pulmonary disease, smear positive cases had a higher CRP than smear negative cases: 67 mg/L (31-122 mg/L) vs 24 mg/L (7-72 mg/L), p < 0.001. HIV positive cases had higher baseline CRPs than HIV negative cases: 75 mg/L (26-136 mg/L) vs 37 mg/L (10-88 mg/L), p <0.001. Differing sites of disease were associated with differences in baseline CRP: locations that might be expected to have a high mycobacterial load (e.g. pulmonary disease and disseminated disease) had a significantly higher CRP than those such as skin, lymph node or CNS disease, where the mycobacterial load is typically low in HIV negative subjects. In a multivariable log-scale linear regression model adjusting for host characteristics and M.tb strain type, infection with the East African Indian strain was associated with significantly lower baseline-CRP (fold-change in CRP 0.51 (0.34-0.77), p < 0.01). CONCLUSIONS: Host and mycobacterial factors are strongly associated with baseline CRP response in tuberculosis. This analysis suggests that there are important differences in innate immune response according to ethnicity, Mtb strain type and site of disease. This may reflect differing mycobacterial loads or host immune responses.

Tools for detection of Mycoplasma amphoriforme: a primary respiratory pathogen?

Mycoplasma amphoriforme is a recently described organism isolated from the respiratory tracts of patients with immunodeficiency and evidence of chronic infection. Novel assays for the molecular detection of the organism by real-time quantitative PCRs (qPCRs) targeting the uracil DNA glycosylase gene (udg) or the 23S rRNA gene are described here. The analytical sensitivities are similar to the existing conventional M. amphoriforme 16S rRNA gene PCR, with the advantage of being species specific, rapid, and quantitative. By using these techniques, we demonstrate the presence of this organism in 17 (19.3%) primary antibody-deficient (PAD) patients, 4 (5%) adults with lower respiratory tract infection, 1 (2.6%) sputum sample from a patient attending a chest clinic, and 23 (0.21%) samples submitted for viral diagnosis of respiratory infection, but not in normal adult control subjects. These data show the presence of this microorganism in respiratory patients and suggest that M. amphoriforme may infect both immunocompetent and immunocompromised people. Further studies to characterize this organism are required, and this report provides the tools that may be used by other research groups to investigate its pathogenic potential.

'Long COVID' syndrome.

SARS-CoV-2 has resulted in a global pandemic and an unprecedented public health crisis. Recent literature suggests the emergence of a novel syndrome known as 'long COVID', a term used to describe a diverse set of symptoms that persist after a minimum of 4 weeks from the onset of a diagnosed COVID-19 infection. Common symptoms include persistent breathlessness, fatigue and cough. Other symptoms reported include chest pain, palpitations, neurological and cognitive deficits, rashes, and gastrointestinal dysfunction. We present a complex case of a previously well 28-year-old woman who was diagnosed with COVID-19. After resolution of her acute symptoms, she continued to experience retrosternal discomfort, shortness of breath, poor memory and severe myalgia. Investigations yielded no significant findings. Given no alternative diagnosis, she was diagnosed with 'long COVID'.

Improved treatment completion for tuberculosis patients: The case for a dedicated social care team.

OBJECTIVES: The increasing social needs of people with Tuberculosis (TB), and the poor adherence to anti-TB therapy (ATT) associated with homelessness, drug or alcohol abuse, and prison history, led us to introduce a social care team (SCT) to support patient engagement with care within this low TB incidence setting. METHODS: Using a risk assessment, patients with social risk factors (SRF) for non-adherence to ATT are identified and a referral made to the SCT, who then provide intensive casework support for areas including homelessness, housing, benefits, debt and immigration. Retrospective data analysis of the social care database from 2017 to 2019 was conducted. Patients who were (n = 170) and were not referred to the SCT (n = 734) were compared. RESULTS: Patients referred were significantly more likely to complete treatment for TB than those not (88.2% versus 77.7% respectively, p = 0.0025), irrespective of receipt of Directly/Video Observed Therapy and adjusting for confounders. CONCLUSIONS: This paper demonstrates important evidence for the positive impact of a dedicated SCT within a TB service, and these improved treatment outcomes provide a strong argument for development of similar SCTs within UK TB services and similar healthcare settings.

Using domiciliary non-invasive ventilator data downloads to inform clinical decision-making to optimise ventilation delivery and patient compliance.

INTRODUCTION: Ventilation parameter data from patients receiving home mechanical ventilation can be collected via secure data cards and modem technology. This can then be reviewed by clinicians and ventilator prescriptions adjusted. Typically available measures include tidal volume (VT), leak, respiratory rate, minute ventilation, patient triggered breaths, achieved pressures and patient compliance. This study aimed to assess the potential impact of ventilator data downloads on management of patients requiring home non-invasive ventilation (NIV). METHODS: A longitudinal within-group design with repeated measurements was used. Baseline ventilator data were downloaded, reviewed and adjustments made to optimise ventilation. Leak, VT and compliance data were collected for comparison at the first review and 3-7 weeks later. Ventilator data were monitored and amended remotely via a modem by a consultant physiotherapist between the first review and second appointment. RESULTS: Analysis of data from 52 patients showed increased patient compliance (% days used >4 hours) from 90% to 96% (p=0.007), increased usage from 6.53 to 6.94 hours (p=0.211) and a change in VT(9.4 vs 8.7 mL/kg/ideal body weight, p=0.022). There was no change in leak following review of NIV prescriptions (mean (SD): 43 (23.4) L/min vs 45 (19.9)L/min, p=0.272). CONCLUSION: Ventilator data downloads, via early remote assessment, can help optimise patient ventilation through identification of modifiable factors, in particular interface leak and ventilator prescriptions. However, a prospective study is required to assess whether using ventilator data downloads provides value in terms of patient outcomes and cost-effectiveness. The presented data will help to inform the design of such a study.

Necrotising pneumonia caused by non-PVL Staphylococcus aureus with 2-year follow-up.

Necrotising pneumonia (NP) is a rare but life-threatening complication of pulmonary infection. It is characterised by progressive necrosis of lung parenchyma with cavitating foci evident upon radiological investigation. This article reports the case of a 52-year-old woman, immunocompetent healthcare professional presenting to Accident and Emergency with NP and Staphylococcus aureus septicaemia. The cavitating lesion was not identified on initial chest X-ray leading to a delay in antimicrobial optimisation. However, the patient went on to achieve a full symptomatic recovery in 1 month and complete radiological recovery at 2-year follow-up. Long-term prognosis for adult cases of NP currently remains undocumented. This case serves as the first piece of published evidence documenting full physiological and radiological recovery following appropriate treatment of NP in an immunocompetent adult patient.

Ipsilateral Dual-Site, Same-Sitting Percutaneous Lung Biopsy: A Feasibility Study.

PURPOSE: Patients with thoracic malignancies often have more than one site of pulmonary, nodal or pleural disease within one hemithorax. In addition, large heterogeneous lesions may comprise distinct, mixed pathological entities. Histological analysis of these lesions can alter tumour staging and treatment options. We investigated the feasibility, safety and benefit of performing image-guided percutaneous lung biopsy (PLB) of two lesions in the same hemithorax at a single sitting. MATERIALS AND METHODS: Ten consecutive outpatients with two or more potential disease foci within the same hemithorax were analysed over a 15-month period. The mean age of the patients was 66 years (range 46-81 years). Patients underwent CT-guided coaxial 20G   core biopsy of both lesions, with separate coaxial punctures for each lesion. Patients were managed as per established local institution ambulatory lung biopsy protocol using small-calibre Heimlich-valve chest drain (HVCD) to treat significant post-PLB pneumothorax in an outpatient setting. Data regarding lesion characteristics, diagnoses and complications were recorded. RESULTS: All 10 patients (n = 20 biopsies, 100% technical success) received informative histological diagnosis on both lesions. This altered management in all cases. Although a high rate of pneumothorax occurred (60%; 6/10), only two of these patients required treatment with HVCD. No other significant complications occurred in those patients with small asymptomatic pneumothoraces or those that required HVCD placement. CONCLUSIONS: Dual-site lung biopsy, performed as a single procedure, is potentially a safe and effective technique for diagnosing patients with multiple thoracic lesions, and can provide useful staging information to guide patient management.