eLetters

282 e-Letters

  • Covid-19: in the footsteps of Ernest Shackleton. Asymptomatic passengers and crew

    Thank you for inviting us to respond to correspondence from Dr. Andrea Vila, entitled “Active searching for pseudo-asymptomatic contacts during outbreak, as containment measure”.

    We would like to establish in greater details what we defined as “asymptomatic” on board our cruise ship. For the first 8 days, prior to the development of fever in the first subject, our 2 ship’s physicians regularly checked for fever in all passengers in a common area, and attended to calls which were predominantly for sea sickness. After day 8, all passengers and crew were seen by one of the two ship’s physicians twice daily, and had body temperature checks. During these visits, symptoms were enquired about. This includes fever, sore throat, cough and myalgias. In mid-March, anosmia was a recognised symptom of Covid-19 infection and was thus included, but dysgeusia and ageusia were not, and thus Vila makes a valid point. However, given that all passengers and crew were seen twice daily between day 8 and day 28, we are confident in the accuracy of the data presented (81% of Covid-19 subjects being asymptomatic), with the above rider. We do not feel that language was a barrier in communication, with the overwhelming number of passengers and crew either having English as their native language, or being fluent in English. In addition one of the ship’s physicians was multilingual.

    Vila also accurately states that asymptomatic subjects may be pre-symptomatic. We have follow-up on all p...

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  • Active searching for ¨pseudo-asymptomatic¨ contacts during outbreak, as containment measure.

    Dear Editor,
    Ing and colleagues reported a cruise outbreak in which a high prevalence of asymptomatic SARS-coV-2 infection was noticed. Viral shedding can occur in the absence of symptoms and before symptom onset, and asymptomatic patients represent an epidemiological problem of great public health significance. However, it’s noteworthy that the huge number of asymptomatic patients (81%), contrasts with a high percentage of severe illness (9.4%) reported on the population of the cruise ship. So, there seems to be a gap between asymptomatic and severe cases of COVID-19, with just 9.6% of mild and moderate clinically disease.
    Cluster studies conducted in Singapore attributed 6.4% to asymptomatic transmission 1.
    Possibly great part of the population of asymptomatic cases, could have been symptomatic but not meeting the ¨case definition¨ at that time, or pre-symptomatic cases (probably the patients had no evaluation after arrival).
    Initial case definition has been periodically updated as more knowledge about COVID-19 was available 2, adding mild or atypical symptoms such as diarrhea, constitutional symptoms, sudden onset of anosmia, ageusia or dysgeusia. The latter were recognized in late March and published in April, thus scarcely known at the time of the report 3-5. As of June, it has been reported that up to 83% patients with mild illness develop anosmia (without nasal obstruction) or dysgeusia as an early or initial manifestation in the absence of o...

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  • Asthmatic children are less susceptible to Covid-19?

    Dear Editor,
    I read with interest Editorial by Wang et al. (1) regarding treatment of asthma in Covid-19 pandemic. It has been reported that allergic diseases, asthma, and chronic obstructive pulmonary disease were not risk factors for SARS-CoV-2 infection as shown in an earlier report from China (2). On the other hand, early data from Centre for Disease Control and Prevention (CDC) in the US suggest a higher rate of asthma in patients hospitalized for severe Covid-19 illness (3). On this background, patients with severe and uncontrolled asthma have also been included to be at increased risk of developing more severe Covid-19 according to CDC (3). It is however unclear whether increased risk is also relevant to the paediatric age group.
    I agree with the authors that asthma control on a population scale may have improved due to reduced pollution, the use of face masks, better medication adherence and reduced smoking. However, these factors are of lesser importance in the paediatric age group. There is variability in the use of facial masks in different countries. It is most probably that lesser severe illness of Covid-19 in children due to the disease (asthma and respiratory allergy) itself that is offering some kind of protection. That protection seems to more than that being offered by adherence to medical treatment alone. Results from a recent cohort study indicate that children with asthma and allergies have reduced angiotensin-converting enzyme-2 (ACE2) gen...

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  • A call for observational data collaboration for sites following Intensive Care Society guidelines for awake prone positioning in COVID-19

    Dear Editor,
    We agree with Koeckerling et al. that awake prone positioning, if proven beneficial, could provide a simple resource-conserving intervention that improves outcomes in COVID-19, especially in the resource-limited countries where even with mitigation strategies critical care bed demand is modelled to outstrip supply by a factor of 25.1,2

    Currently, our knowledge about prone positioning is extrapolated from studies in non-awake, mechanically ventilated patients and so these proposed benefits remain theoretical.3-6
    In addition to the various small-scale observational studies mentioned by Koeckerling et al., a recently published observational study of 24 awake COVID-19 patients concluded that awake prone positioning was well tolerated. However, the numbers were too small to confirm or refute any benefit in this population.7 Randomised control trial (RCT) is the gold standard for evidence in awake prone positioning in COVID-19 population. However, RCT will be a very difficult approach for this intervention due to the likelihood of a lack of equipoise amongst clinicians to recruit. Following national guidelines, many departments would implement this intervention as the standard of care. Awake prone positioning also appears to be a safe intervention in awake patients and may slow the respiratory deterioration in selected patients with COVID-19.1

    Following the recent Intensive Care Society (ICS) guideline, clinicians within our institution ha...

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  • The Yentl syndrome effect on Idiopathic pulmonary fibrosis

    “The Yentl Syndrome” coined in 1991 by Bernadine Healy is the different course of action that the treating physicians usually follow for women than for men (1,2). The name is taken from the 1983 film Yentl starring Barbra Streisand in which her character plays the role of a male in order to attend school and study the Talmud. Being "just like a man" has historically been a price women have had to pay for equality. Throughout the centuries women, considered different and second-class from men, have too often been treated less than equally in various aspects of life, including education and health care (2). Bernadine Healy (1) pointed out in an editorial for the two studies (3,4) published in the same journal demonstrating that women who are hospitalized for coronary heart disease undergo fewer major diagnostic and therapeutic procedures than men as physicians pursue a less aggressive management approach in women than in men, despite greater cardiac disability in women.
    Later, two studies (5,6) demonstrate under-treatment of women with medication, including lower rates of aspirin and ACE inhibitor use in stable women compared with men, as well lower rates of ACE inhibitor, beta-blocker and statin medication in acute coronary syndrome women compared with men. Both studies also show gender differences in use of procedures, where stable women undergo more repeat angiography, whereas acute coronary syndrome women undergo fewer angiograms, percutaneous coronary in...

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  • Stop respiratory support? - we will take some convincing!

    Langley RJ*1, Pabary R1, Trucco F1, Bush A1.

    Department of Respiratory Paediatrics and Sleep Medicine, Royal Brompton Hospital, London, UK
    *Corresponding author - rosslangley@nhs.net
    No conflicts of interest

    Dear Editor

    Whilst we recognise the need for caution and careful planning when considering the ongoing use of home non-invasive ventilation (NIV) and continuous positive airway pressure (CPAP) in children during the COVID-19 pandemic, we read with some concern the recent views by Barker et al.1 recommending the discontinuation of respiratory support unless “medically necessary to support life”.

    There is undoubtedly a risk to caregivers and relatives of potential aerosolisation of infectious material. This is true not just of COVID-19, but also potentially harmful viruses such influenza A, respiratory syncytial virus (RSV) and many other respiratory viral pathogens which commonly infect children. This is not a new threat, but a new virus.

    However, advising withdrawal of CPAP/NIV support, which is always prescribed for sound medical reasons in children, is not just misplaced but potentially dangerous.

    Firstly, there is a real danger in providing such advice at time of crisis when one cannot fully assess or appreciate the impact of withdrawing treatment on “peacetime” health. Children requiring respiratory support often struggle to comply and reduced use over time would undoubte...

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  • British Thoracic Society (BTS) position statement on environmental and lung health

    In a position statement published in March, the British Thoracic Society (BTS) recommended that ‘where a new class of inhaler is commenced, this is a Dry Powder Inhaler (DPI)’. The statement went on to state that ‘ Where patients are using several classes of inhalers and poor inhaler technique is identified with one device, that the DPI class is prioritised if the patient is able to use these safely. Similarly, future and
    additional inhalers would ideally also be DPIs; and that during all respiratory reviews, prescribers
    recommend low carbon alternatives to patients currently using Pressured Metered Dose Inhalers
    (pMDIs), where patients are able to use these safely’.

    We are extremely worried by the potential impact that these recommendations could have, since they come from a trusted body which has the reputation to place the health, needs and safety of patients above all. This statement encourages prescribers to change their prescribing habits, not to patient care and safety, but to the systematic exclusion of metered-dose inhalers in favour of dry powder devices for highly debatable environmental concerns. Since the vast majority of prescribers are not experts of inhalation therapy, such guidance may put some patients in danger and lead to a loss of opportunity to optimize care.

    Metered-dose inhalers are used much more reliably with spacers by young children and those with impaired respiratory function. It is well established (1) that pat...

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  • Response to Kennedy et al

    We thank Dr Kennedy and colleagues for their interest in our recent
    paper comparing outcomes after surgery and SABR radiotherapy in
    stage I non-small cell lung cancer (1,2) .
    We agree that intraoperative nodal upstaging can be a cause of stage
    migration in the surgical arm but not the SABR arm, and so could act
    as a potential bias in an observational study. This might
    overestimate the benefit of surgery compared to SABR. The Society
    for Cardiothoracic Surgery Database Project reported 2155 patients
    undergoing lung cancer resections in England from 2014-16, and
    found that over 13% of patients underwent nodal upstaging when
    their resection pathology was analysed (3) .
    The information bias inherent in having full pathological data
    available for surgical but not SABR cases leads to other potential
    problems with analysis. All patients undergoing surgery have a
    pathological analysis confirming the cancer and its stage, while 240
    of the 476 patients treated with SABR were treated without a
    pathological diagnosis. A recent prospective UK study found that
    14% of patients operated on for presumed lung cancer had benign
    disease on intraoperative frozen section biopsy or final pathology (4) .
    Assuming that this surgical false negative rate approximates the rate
    in the suspected early clinical stage patients treated with SABR, then
    around 7% of our SABR arm may...

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  • Response to Laura W Lund, and Jeremy D Kimmel ALung Technologies January 16, 2020

    The SUPERNOVA trial was a prospective observational phase II study supported by an unrestricted grant from three companies (Alung, Maquet, and Novalung) and by the European Society of Intensive Care Medicine (ESICM). The three companies provided equipment and covered costs for data monitoring, site visits, and insurance fees. The grant (€171,000) was made available to ESICM that supported data collection and analysis, and all administrative costs. As owner of the data, ESICM appointed the two principal investigators (AC and VMR) and the independent Data and Safety Monitoring Board (Jukka Takala, Chair). The study included 95 patients. The proportion of patients who achieved ultra-protective settings by 24 hours was 82%. Number of patients that experienced severe and ECCO2R-related adverse events was 2 (2%) and 37 (39%)1. Retrospective analysis of these data showed that (a) efficacy of ECCO2R to facilitate further reduction of tidal volume was lower with smaller artificial lungs and running at lower blood flow than with larger artificial lungs and running at a higher blood flow2; (b) haemolysis and bleeding was higher with the former than with the latter2; (c) applying these data to a previously described theoretical model3 we predicted that incorporating higher CO2 removal rates as factors to design randomized clinical trial might substantially reduce screening and sample size requirements4.
    In her letter, Dr Lund, expressed several concerns about these findin...

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  • Nodal staging should not be left out of the equation

    We read with interest the report from Khakwani and colleagues comparing real-world outcomes for patients with stage I NSCLC undergoing surgery and stereotactic radiotherapy (SABR) (Ref 1), together with the accompanying editorial (Ref 2). Given the failure to recruit to previous randomised trials designed to compare these treatments, analyses of large national datasets are vital to improve our understanding of how best to manage this patient group.

    One additional possible explanation for the worse outcome in the SABR cohort relates to occult nodal involvement. Inaccuracies in clinical staging are well described; one analysis documented that 34% of patients are under-staged by pre-operative work-up (Ref 3). Patients with occult nodal disease would have been identified in the surgical group by intraoperative systematic nodal staging, and would therefore have been excluded from analysis of the Stage I cohort presented here (Ref 1). Patients who are similarly under-staged prior to SABR treatment will remain in the Stage I cohort for analysis, yet will have worse outcomes by virtue of their more advanced disease. Comparing outcomes on an intention-to-treat basis using pre-treatment stage may minimise this bias.

    We agree with the authors that residual confounding may be an important factor explaining these results, and that examination of cause of death is instructive. In our single centre study, cause of death was compared (on an intention to treat basis) between...

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