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.

First light of the Gemini Planet imager.

The Gemini Planet Imager is a dedicated facility for directly imaging and spectroscopically characterizing extrasolar planets. It combines a very high-order adaptive optics system, a diffraction-suppressing coronagraph, and an integral field spectrograph with low spectral resolution but high spatial resolution. Every aspect of the Gemini Planet Imager has been tuned for maximum sensitivity to faint planets near bright stars. During first-light observations, we achieved an estimated H band Strehl ratio of 0.89 and a 5-σ contrast of 10(6) at 0.75 arcseconds and 10(5) at 0.35 arcseconds. Observations of Beta Pictoris clearly detect the planet, Beta Pictoris b, in a single 60-s exposure with minimal postprocessing. Beta Pictoris b is observed at a separation of 434 ± 6 milliarcseconds (mas) and position angle 211.8 ± 0.5°. Fitting the Keplerian orbit of Beta Pic b using the new position together with previous astrometry gives a factor of 3 improvement in most parameters over previous solutions. The planet orbits at a semimajor axis of [Formula: see text] near the 3:2 resonance with the previously known 6-AU asteroidal belt and is aligned with the inner warped disk. The observations give a 4% probability of a transit of the planet in late 2017.

In-focus wavefront sensing using non-redundant mask-induced pupil diversity.

Wavefront estimation using in-focus image data is critical to many applications. This data is invariant to a sign flip with complex conjugation of the complex amplitude in the pupil, making for a non-unique solution. Information from an in-focus image taken through a non-redundant pupil mask (NRM) can break this ambiguity, enabling the true aberration to be determined. We demonstrate this by priming a full pupil Gerchberg-Saxton phase retrieval with NRM fringe phase information. We apply our method to measure simulated aberrations on the segmented James Webb space telescope (JWST) mirror using full pupil and NRM data from its near infrared imager and slitless spectrograph (NIRISS).

Performance of the Gemini Planet Imager's adaptive optics system.

The Gemini Planet Imager's adaptive optics (AO) subsystem was designed specifically to facilitate high-contrast imaging. A definitive description of the system's algorithms and technologies as built is given. 564 AO telemetry measurements from the Gemini Planet Imager Exoplanet Survey campaign are analyzed. The modal gain optimizer tracks changes in atmospheric conditions. Science observations show that image quality can be improved with the use of both the spatially filtered wavefront sensor and linear-quadratic-Gaussian control of vibration. The error budget indicates that for all targets and atmospheric conditions AO bandwidth error is the largest term.

Toscana virus encephalitis following a holiday in Sicily.

We report a case of Toscana virus encephalitis. This emerging pathogen is among the three most common causes of meningoencephalitis in Europe during the warm season, yet remains under-recognised. Doctors should consider Toscana virus infection in patients presenting with neurological symptoms who have a relevant exposure history during the summer months.

Fizeau interferometric cophasing of segmented mirrors: experimental validation.

We present an optical testbed demonstration of the Fizeau Interferometric Cophasing of Segmented Mirrors (FICSM) algorithm. FICSM allows a segmented mirror to be phased with a science imaging detector and three filters (selected among the normal science complement). It requires no specialised, dedicated wavefront sensing hardware. Applying random piston and tip/tilt aberrations of more than 5 wavelengths to a small segmented mirror array produced an initial unphased point spread function with an estimated Strehl ratio of 9% that served as the starting point for our phasing algorithm. After using the FICSM algorithm to cophase the pupil, we estimated a Strehl ratio of 94% based on a comparison between our data and simulated encircled energy metrics. Our final image quality is limited by the accuracy of our segment actuation, which yields a root mean square (RMS) wavefront error of 25 nm. This is the first hardware demonstration of coarse and fine phasing an 18-segment pupil with the James Webb Space Telescope (JWST) geometry using a single algorithm. FICSM can be implemented on JWST using any of its scientic imaging cameras making it useful as a fall-back in the event that accepted phasing strategies encounter problems. We present an operational sequence that would co-phase such an 18-segment primary in 3 sequential iterations of the FICSM algorithm. Similar sequences can be readily devised for any segmented mirror.

Fizeau interferometric cophasing of segmented mirrors.

Segmented mirror telescope designs address issues of mechanical rigidity, but introduce the problem of aligning, or cophasing, the separate segments to conform to the optimum mirror shape. While several solutions have been widely adopted, a few difficulties persist - the introduction of non-common path errors and an artificial division of the problem into coarse and fine regimes involving separate dedicated hardware solutions. Here we propose a novel method that addresses many of these issues. Fizeau Interferometric Cophasing of Segmented Mirrors (FICSM) uses non-redundant sparse aperture interferometry to phase mirror segments to interferometric precision using unexceptional science hardware. To show the potential of this technique we numerically simulate conditions on NASA's James Webb Space Telescope (JWST), showing that the FICSM method has the potential to phase the primary mirror from an initial state with segment-to-segment pistons as large as 150 microns and tilts as large as 0.5 arcseconds, to produce a final state with 0.75 nm rms segment-to-segment pistons and 3.7 mas rms segment tilts. The image undergoes monotonic improvement during this process. This results in a rms wavefront error of 3.65 nm, well below the 100 nm requirement of JWST's coarse phasing algorithm.

Carbapenemase-producing organism (CPO) colonisation at a district general hospital: universal screening may help reduce transmission.

OBJECTIVE: Assess the potential of hospital-wide routine screening by determining the prevalence and incidence of carbapenemase-producing organisms (CPOs) isolated from rectal screens at Barnet and Chase Farm Hospitals. METHODS: 3,553 samples were collected between 01/12/2018 and 31/08/2019: from adult critical care wards (universal screening - admission, discharge and weekly), from medical wards with risk-factor based screening according to the prevailing Public Health England (PHE) carbapenemase-producing Enterobacteriaceae (CPE) screening guidelines, or on an ad hoc basis. Prevalence was defined as previously documented positive CPO colonisation, or new positive status, as a proportion of all eligible samples. Incidence was defined as all newly positive patients per 1,000 patient-days. RESULTS: Overall CPO prevalence was 2.1% (95% CI: 1.61-2.58%). Inpatient prevalence was significantly higher at 2.6% vs outpatient at 0.5% (p < 0.001). Incidence was 0.44 per 1,000 patient-days (95% CI: 0.33-0.57), with a rate ratio between Barnet and Chase Farm of 4.9 (p = 0.013). Incidence was highest where universal screening strategy was applied (3.9 per 1000 patient-days, 95% CI: 2.4-5.91). This was 2.5 times higher than risk-factor based screening (p = 0.005) and 23.5 times that of wards without routine surveillance implemented (p < 0.001). CONCLUSION: Surveillance remains a cornerstone in controlling CPO transmission. Our local incidence, lacking hospital-wide screening, significantly exceeded the reported UK average. Universal screening could help to uncover the true prevalence and incidence of CPO, thereby providing the necessary information to properly control transmission, reducing nosocomial outbreaks and ultimately reducing the overall cost to healthcare.

Epidemiology and control measures of an OXA-48-producing Enterobacteriaceae hospital outbreak.

Carbapenemase-producing Enterobacteriaceae (CPE) are a significant challenge to healthcare and infection prevention and control teams. In the UK, OXA-48-like carbapenemases are frequently reported. We describe an outbreak of OXA-48-like producing Enterobacteriaceae and the control measures that proved effective in containing further spread. AIM: To describe epidemiologic and laboratory features of outbreak and highlight key control interventions. FINDINGS: Following the introduction of an increased sensitivity CPE screening protocol, OXA-48-like CPE were identified in screening and clinical samples from 96 patients across five hospital wards between November 2017 and July 2018. Klebsiella pneumoniae and Enterobacter cloacae were the most frequently isolated organisms, although a range of OXA-48-like positive organisms were identified. The outbreak was contained utilising certain key interventions, including the modification of laboratory screening processes, engagement of hospital senior management, clear and frequent communication and a strong 'ward presence' by the infection prevention and control team (IPCT). CONCLUSION: Our report describes how a change in laboratory CPE screening process unmasked a CPE outbreak. The range of bacterial species harbouring the OXA-48-like mechanism suggested plasmid-mediated transfer of resistance. The timely implementation of interventions using a clinical, 'ward-based' approach to infection prevention and control highlights the importance of behavioural change in infection control interventions and enabled the termination of a large outbreak without recourse to environmental sampling, major remedial construction work or extensive molecular strain or plasmid typing.

Pneumococcal vaccination in people living with HIV.

Streptococcus pneumoniae is the leading bacterial opportunistic infection (OI) in HIV positive individuals. Anti-retroviral treatment (ART) reduces their risk of Invasive Pneumococcal Disease (IPD), however, it remains 20- to 40-fold greater than that of the general population. In HIV-infected adults, pneumococcal vaccination (PCV) induces more durable and functional antibody responses in individuals on ART at the time of vaccination than in ART-naive adults, independently of the baseline CD4+ cell count. National guidelines in the UK recommend vaccination in HIV-infected adults with CD4 count >200cells/mL and advise that it be considered for those with CD4 count <200cells/mL(3). We report data on IPD from a London HIV cohort of 3500 north-east London patients from 2009 to 2012. IPD was defined as a positive pneumococcal culture from blood, CSF, joint aspirate or pericardial fluid. HIV positive cases were identified by cross-referencing hospital identifiers with a positive HIV Ab/Ag test result or HIV viral load test result on the virology database. There were a total 189 cases of Invasive Pneumococcal Disease identified over the three years. 4.8% (n=9) were known to be HIV positive at the time of their Invasive Pneumococcal infection. The serotypes of S. pneumoniae in the HIV positive cases included 3, 7F, 10F, 19A (n=2), 19F and 31. The estimated incidence of IPD in our HIV cohort was 85.7 per 100,000, (based on an overall HIV cohort size of 3500) which is significantly higher when compared to the general population in London (local epidemiological data reported the incidence rate for IPD at 7.5 per 100,000 in London). Given the higher burden of Invasive Pneumococcal Disease in this cohort, low levels of vaccination, and the predominance of vaccine sensitive strains in our cases, vaccination and strategies to improve vaccine uptake is a priority in this at risk group.

Systematic review, meta-analysis and economic modelling of molecular diagnostic tests for antibiotic resistance in tuberculosis.

BACKGROUND: Drug-resistant tuberculosis (TB), especially multidrug-resistant (MDR, resistance to rifampicin and isoniazid) disease, is associated with a worse patient outcome. Drug resistance diagnosed using microbiological culture takes days to weeks, as TB bacteria grow slowly. Rapid molecular tests for drug resistance detection (1 day) are commercially available and may promote faster initiation of appropriate treatment. OBJECTIVES: To (1) conduct a systematic review of evidence regarding diagnostic accuracy of molecular genetic tests for drug resistance, (2) conduct a health-economic evaluation of screening and diagnostic strategies, including comparison of alternative models of service provision and assessment of the value of targeting rapid testing at high-risk subgroups, and (3) construct a transmission-dynamic mathematical model that translates the estimates of diagnostic accuracy into estimates of clinical impact. REVIEW METHODS AND DATA SOURCES: A standardised search strategy identified relevant studies from EMBASE, PubMed, MEDLINE, Bioscience Information Service (BIOSIS), System for Information on Grey Literature in Europe Social Policy & Practice (SIGLE) and Web of Science, published between 1 January 2000 and 15 August 2013. Additional 'grey' sources were included. Quality was assessed using quality assessment of diagnostic accuracy studies version 2 (QUADAS-2). For each diagnostic strategy and population subgroup, a care pathway was constructed to specify which medical treatments and health services that individuals would receive from presentation to the point where they either did or did not complete TB treatment successfully. A total cost was estimated from a health service perspective for each care pathway, and the health impact was estimated in terms of the mean discounted quality-adjusted life-years (QALYs) lost as a result of disease and treatment. Costs and QALYs were both discounted at 3.5% per year. An integrated transmission-dynamic and economic model was used to evaluate the cost-effectiveness of introducing rapid molecular testing (in addition to culture and drug sensitivity testing). Probabilistic sensitivity analysis was performed to evaluate the impact on cost-effectiveness of diagnostic and treatment time delays, diagnosis and treatment costs, and associated QALYs. RESULTS: A total of 8922 titles and abstracts were identified, with 557 papers being potentially eligible. Of these, 56 studies contained sufficient test information for analysis. All three commercial tests performed well when detecting drug resistance in clinical samples, although with evidence of heterogeneity between studies. Pooled sensitivity for GenoType® MTBDRplus (Hain Lifescience, Nehren, Germany) (isoniazid and rifampicin resistance), INNO-LiPA Rif.TB® (Fujirebio Europe, Ghent, Belgium) (rifampicin resistance) and Xpert® MTB/RIF (Cepheid Inc., Sunnyvale, CA, USA) (rifampicin resistance) was 83.4%, 94.6%, 95.4% and 96.8%, respectively; equivalent pooled specificity was 99.6%, 98.2%, 99.7% and 98.4%, respectively. Results of the transmission model suggest that all of the rapid assays considered here, if added to the current diagnostic pathway, would be cost-saving and achieve a reduction in expected QALY loss compared with current practice. GenoType MTBDRplus appeared to be the most cost-effective of the rapid tests in the South Asian population, although results were similar for GeneXpert. In all other scenarios GeneXpert appeared to be the most cost-effective strategy. CONCLUSIONS: Rapid molecular tests for rifampicin and isoniazid resistance were sensitive and specific. They may also be cost-effective when added to culture drug susceptibility testing in the UK. There is global interest in point-of-care testing and further work is needed to review the performance of emerging tests and the wider health-economic impact of decentralised testing in clinics and primary care, as well as non-health-care settings, such as shelters and prisons. STUDY REGISTRATION: This study is registered as PROSPERO CRD42011001537. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Noninvasive assessment of endothelial dysfunction by brachial artery flow-mediated dilatation in prediction of coronary artery disease in Indian subjects.

BACKGROUND: A noninvasive technique for testing endothelial function by ultrasound measurement of flow-mediated dilatation has recently generated considerable interest as a marker of atherosclerosis, and in the prediction of clinical coronary events and coronary artery disease. METHODS AND RESULTS: We measured the flow-mediated dilatation of the brachial artery (endothelium-dependent vasodilatation) in 136 subjects, with or without evidence of coronary artery disease. Endothelial dysfunction was diagnosed if flow-mediated dilatation was less than 4.5%. Of the 136 subjects (age group 40-70 years) recruited for the study, 94 were males and 42 females. Sixty-eight subjects had evidence of coronary artery disease as diagnosed by documented hospitalization due to myocardial infarction or acute coronary syndrome, proved by coronary angiography when feasible or noninvasive cardiac evaluation. Endothelial dysfunction was detected in 90 subjects (66.2%). Prevalence of coronary artery disease was higher among subjects with endothelial dysfunction compared to those without (57.5% v. 34.7%, p=0.013). Prevalence of endothelial dysfunction was significantly higher among subjects with coronary artery disease as compared to those without coronary artery disease (76.4% v. 55.8%, p=0.012). The present study showed a sensitivity of 76%, specificity of 44%, positive predictive value of 58% and negative predictive value of 65% for endothelial dysfunction in the prediction of coronary artery disease. Multiple regression analysis using coronary artery disease as a dependent variable revealed a statistically significant association with endothelial dysfunction (p=0.033) even after the inclusion of traditional risk factors into the model. CONCLUSIONS: We conclude that endothelial dysfunction shows a strong association with coronary artery disease and can be a useful noninvasive tool for the evaluation of coronary artery disease.

Job satisfaction and stress levels among anaesthesiologists of south India.

BACKGROUND: Stress being high among practicing anaesthesiologists has effects on the quality of life. Methods to mitigate the stress have to be ensured to achieve job satisfaction. METHODS: A survey was conducted through a questionnaire to know the various aspects of job satisfaction and job stress. The results of the data obtained were analyzed. RESULTS: An anaesthetists work area may vary from a small private hospital to a large tertiary centre.Depending on the number of anaesthetists in a particular hospital, the working hours and on call duties would be distributed. Overworked anaesthetists are prone to burnout due to sleep deprivation. This could lead to fatigue related error. Lesser the number of anaesthetists would mean less support from colleagues in the event of complications. Having a good rapport with surgical colleagues also helps to prevent stress.Anaesthesiologists should have adequate monitors to avoid error in judgement. Chronic stress has serious health hazards. Keeping updated with latest developments in our field helps to improve the quality of care provided. Anaesthetists should also receive the recognition and remuneration due to them. CONCLUSION: To improve the quality of care provided to a patient,anaesthesiologists must cope with job stress. An anaesthetist must enjoy the work rather than be burdened by it.