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26th June 2020
Many patients who die after infection with COVID-19 develop respiratory complications including severe pneumonia and respiratory failure.
Treatment options are currently limited, although recently dexamethasone has been shown to reduce deaths by a third of hospitalised patients with severe respiratory complications.1
While the search for a vaccine continues several anti-viral treatments have been explored. COVID-19 is an RNA virus and requires a protease enzyme, chymotrypsin-like protease (3CLpro) for replication and because lopinavir and ritonavir are protease inhibitors, it was thought that these agents could represent an effective treatment for the virus.
Sadly, an early Chinese trial used the combination of lopinavir and ritonavir in hospitalised patients with COVID-19 showed no benefit from the addition of the two anti-viral agents compared to standard care.2
However, studies in mice demonstrated that another anti-viral, remdesivir, had greater activity than either lopinavir and ritonavir against Middle East respiratory syndrome (MERS), another coronavirus3 and might therefore represent a more promising treatment for those with COVID-19.
Remdesivir was developed by Gilead Sciences after the company embarked on a programme to identify treatments for RNA-based viruses such as Ebola and other coronaviruses.4
In their search for an effective agent, one candidate which emerged from early testing was named GS-5734 (remdesivir) which was shown to have anti-viral activity against Ebola virus in rhesus monkeys.5
In addition, the drug also had in vitro activity against many different viruses including other coronaviruses such as severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS).6
However, when the in vivo effectiveness of remdesivir was tested in a clinical trial against Ebola virus, use of the drug was terminated early due to a lack of efficacy compared to other agents.7
Remdesivir is a pro-drug that requires activation within a cell where it is converted within cells to remdesivir triphosphate, a structural analogue of adenosine, one of the nucleotides that is incorporated by the viral RNA polymerase enzyme into newly formed RNA. Because the drug is an analogue rather than an actual nucleoside, further replication of the virus is halted.8
Remdesivir currently has no licensed indications but in May 2020, the MHRA issued a scientific opinion under the early access to medicines scheme, to allow the drug to be used as a treatment for COVID-19.9
Despite the lack of a license, the drug is now indicated for the treatment of people aged 12 years and over, weighing at least 40kg and hospitalised with either suspected or confirmed SAR-CoV-2 infection and severe disease.
The suggested dose for patients requiring invasive ventilation is 200mg on Day 1 followed by a daily maintenance dose of 100 mg for nine days. In contrast, for patients not requiring ventilation, the same dosage is recommended but for five rather than 10 days.
To date, two randomised trials and one observational study exploring the efficacy of remdesivir have been published.10–12 These results have been summarised in a Cochrane review,13 which clearly show that compared to placebo, the 14-28-day all-cause mortality is not significantly different to placebo (relative risk (RR) = 0.74, 95% confidence interval (95% CI) 0.40 – 1.37).
However, remdesivir was significantly better than placebo at reducing the need for supportive measures, for example, non-invasive ventilation or mechanical ventilation in patients with a WHO progression score (which measures disease severity, ranging from 1 = not hospitalised to 8 = death) level 6/7 or above between days 14 to 28 (RR = 0.76, 95% CI, 0.62 – 0.93).
NICE has produced a review of the current available evidence and concluded that there is “some benefit with remdesivir compared with placebo for reducing supportive measures” but that “no statistically significant differences were found for mortality and serious adverse events”.14
The NICE review did not include one recent open label study which randomised 397 patients, not requiring mechanical ventilation, to remdesivir for either five or 10 days with a median duration of treatment of five days.
By day 14, 64% of patients given remdesivir for 5 days vs 54% for 10 days, had a clinical improvement of 2 or more points, on a scale ranging from 1 (death) to 7 (not hospitalised).15 However, the study did not include a control group and so the magnitude of the observed benefit could not be determined.
The results of a study published on 25 June 2020 the European Medicines Agency (EMA) recommended granting a conditional marketing authorisation for remdesivir (brand name Veklury) for the treatment of adults and adolescents 12 years and over with pneumonia who require supplemental oxygen.16
This decision was based on the results of the National Institute of Allergy and Infectious Diseases (NIAID) trial which evaluated the effectiveness of a 10-day course of the drug in over 1,000 hospitalised patients compared with placebo.
According to the EMA, the NISAID study found that patients treated with remdesivir recovered after about 11 days compared with 15 days for those taking placebo.
For patients with mild to moderate disease there was no difference compared with placebo but an effect was seen in those with severe COVID-19, where time to recovery was 12 days versus 18 days.
However, there were no differences for patients who started remdesivir when they were already in receipt of mechanical ventilation or extracorporeal membrane oxygenation. The difference in 28-day mortality is currently not available.
The EMA has recommended a treatment regime of 200mg on day one, followed by 100mg daily for at least four days.
In summary, and to date, there is some limited evidence to indicate that remdesivir reduces the time to recovery in patients with severe disease which has prompted the EMA to approve the use of the drug.
Nevertheless, the available data has yet to reveal improvements in 28-day mortality. In a rapidly changing world, the results of further comparative and ongoing trials will hopefully add more concrete evidence on whether remdesivir is a valuable addition to the currently available treatments for patients with COVID-19.
References
23rd June 2020
The team retrospectively analysed the duration of antibiotic therapy for 101 patients discharged to the community from general surgery and general medical services at a large academic medical centre.
Included patients had one of the following diagnoses: uncomplicated urinary tract infection (uUTI), complicated (cUTI), community-acquired pneumonia (CAP) and hospital-acquired pneumonia (HAP). The total duration of antibiotic therapy was calculated as the sum of the in-patient and outpatient prescriptions. Guideline recommended treatment durations were 3 days (uUTI), 5 days (CAP) and 7 days (cUTI and HAP). Overall, only 3% of patients had antibiotic treatment durations which met these recommendations with the median duration beyond guidelines being 4 (range 2 – 7) days.
For example, the median duration was 5 days longer than recommended for cUTI and 2 and 3 days for CAP and HAP. In addition, more than 75% of patients received antibiotic courses exceeding 7 days, which on average, resulted in patients having 3.8 days of unnecessary antibiotics.
The authors suggest that hospital pharmacists have an important role to play in antibiotic stewardship by reviewing the duration of discharge prescriptions.
Reference
Brower KI et al. Duration of antibiotic therapy for general medicine and general surgery patients throughout transitions of care: an antibiotic stewardship opportunity for non-infectious disease pharmacists. Hospital Pharmacy 2020; June 14 doi.org/10.1177/0018578720928265
It also provides advice for transplant and referral centres on how best to run services during the COVID-19 pandemic and to protect staff and patients from infection.
Service organisation
NG178 suggests that renal networks collaborate to manage renal pathways during the pandemic to ensure that sites are COVID secure for both transplant and recipient assessment and follow-up after transplantation. It is recommended that alternative sites are used for parts of the pathway following human tissue authority guidance.
Prior to re-opening or expanding transplant services, centres are required to be confident that they have appropriate governance arrangements in place for data collection and that they are able to meet all the service specification requirements and have the capability for rapid COVID-19 testing and COVID-19 secure areas for recipients and donors.
Centres need to also discuss re-opening plans with the NHS blood and transplant and take account of the NHS Blood and Kidney advisory group guidance as well as NHS commissioners and other associated non-transplanting centres and local transplant centres if appropriate. They also need to communicate their re-opening plans with patients and their families and discuss the risks and benefits in the current pandemic.
NG178 also suggests that transplant and non-transplant centres use remote phlebotomy services as a way of minimising face-to-face contact and consider COVID-19 testing for both patients on the waiting list in line with any local polices and frontline staff.
Transplant recipients
Among patients who have had a new kidney, NG178 advices that health professionals review the UK government advice on shielding for patients and their families and explain any current risks. It is also important that patients and families are given advice on attending appointments and how to seek help if they become unwell. Staff should ensure that patients are added to their GP shielding list and that when being cared for, staff follow the UK government guidance on infection prevention and control. NG178 advises that staff assess whether patients taking immunosuppressants can have less frequent blood tests for routine monitoring.
NG178 notes that if patients taking immunosuppressants become unwell with respiratory symptoms, COVID-19 should not be automatically considered as the first diagnosis as other infective and non-infective causes may lead to symptoms and immunosuppressant treatment can result in atypical COVID-19 symptoms. However, if COVID-19 is diagnosed then immunosuppressant therapy can be modified following guidance from the British Transplantation Society and Renal Association.
Transplant donors
In the case of deceased donors, NG178 signposts clinical staff to advice on COVID-19 screening by the NHS Blood and Transplant Kidney Advisory group.
For living donors, it is advised that patients are fully informed of the implications of kidney donation in the context of COVID-19 and how risks can be managed. Transplantation should be delayed if patients develop COVID-19 until at least 28 days after becoming symptom-free and after a negative nasopharyngeal swab test for COVID-19. NG178 makes reference to the British Transplantation Society guidance for clinicians on consent for solid organ transplantation in the context of COVID-19.
Donation should not be undertaken until both the donor and recipient have tested negative for COVID-19.
Patients considered for kidney transplant
NG178 discusses the importance of informing patients of the risks and benefits of transplantation in the context of COVID-19. While this advice should be tailored to the individual needs of the patient, it should follow the advice provided to transplant recipients as described above.
Care at the time of the transplant
It is strongly advised in NG178 that transplant centres review induction and immunosuppression regimes to assess an individual’s immunosuppression burden in relation to COVID-19. All patients should be admitted earlier than usual to minimise cold ischaemia time and to allow for checking their history of social distancing and swab testing for COVID-19 performed together with a respiratory assessment.
A CT chest scan is not routinely required for patients without COVID-19 symptoms and the transplant or immunosuppression should not begin until the patient has tested negative for COVID-19. It is also vital that for those who require dialysis after transplantation this should be done in a COVID-19 secure area.
Patient communication and minimising infection risk
NG178 discusses the importance of communicating with patients, their families and carers to support their mental wellbeing during the COVID-19 pandemic to alleviate any anxieties or concerns they might have about the virus. The guideline suggests signposting patients to relevant sources of information such as Kidney Care UK coronavirus guidance, the National Kidney Federation, give a kidney, the UK government guidance mental health and wellbeing aspects of COVID-19, the NHS Blood and Transplant service and any relevant local kidney patient organisations.
NG178 advises staff to remind all patients not to change their current medication unless advised to do so by their specialist team and to keep a current list of their medicines in case they become unwell, in which case they should contact their specialist team.
NG178 recommends minimising face-to-face consultations and to make use of either telephone/video or to contact patients via email or text messaging and to issue electronic rather than paper prescriptions. However, if face-to-face appointments are necessary, staff should minimise the time patients spend in the waiting area through careful scheduling of appointments, discouraging early attendance and by asking patients to remain in their transport vehicle until they receive a text message informing them that they are ready to be seen. NG178 strongly recommends a “clean route” through the hospital and that treatments and prescriptions are delivered and dispensed rapidly.
Patients should be advised to contact both their renal teams and the NHS111 online coronavirus service if they believe that they are infected with COVID-19, but if seriously ill to contact 999.
Patients known or suspected of having COVID-19
Where a patient is known or suspected of having COVID-19, NG178 advises staff to follow the UK government guidance on infection prevention and control. However, if COVID-19 is detected at a later stage and the patient was not initially isolated, the NG178 suggests following the IK government guidance on the management of exposed healthcare workers and patients.
In contrast, if a patient not known to be infected displays COVID-19 symptoms when first presenting, NG176 advises staff to follow the UK government guidance on investigation and initial clinical management of possible cases.
Healthcare workers
In cases where staff are known/suspected of having COVID-19, or live in a household where another person is known/suspected of having the virus, they should self-isolate and only return to work in accordance with the UK government guidance on stay at home for households with possible COVID-19 infection. If self-isolating staff are still able to work, recommended roles include undertaking telephone or video consultations and participation in virtual multidisciplinary meetings, helping to identify patients who can be monitored remotely and those who might require more support as well as performing any routine tasks which can be done remotely.
NG178 is available online and interested readers should check this version for further updates.
The clinical course of COVID-19 is variable, with some patients being asymptomatic or experiencing very mild symptoms and others critically ill. There are also those in the middle, not sick enough to require hospitalisation but, nevertheless, experiencing significant and prolonged illness. Many people have described their experiences in blogs and on Twitter. Cough, breathlessness, chest tightness, pain on breathing in, general exhaustion and aching pains all feature prominently. These are frightening experiences, especially for people who have otherwise been healthy and largely untroubled by coughs and colds.
As SARS-CoV-2 began to spread round the world, thoughts turned to repurposing of existing drugs and researchers began to trawl the literature to identify possible candidates. One drug of interest is indomethacin – a drug that has both anti-inflammatory and antiviral actions. Its antiviral actions were first discovered in 2006 in the wake of the SARS-CoV outbreak.1 It was subsequently shown to be active against SARS-CoV-2 in vitro and against canine coronavirus in vivo.2 Importantly, the antiviral effects were seen at normal anti-inflammatory dose levels. Primary care physicians in New York, faced with large numbers of sick patients, (people with intractable coughing, pain with inspiratory effort, etc) have been prescribing indomethacin for them. They have found that it quickly stops the cough, relieves the pains and leads to a feeling of overall wellbeing – benefits that were not seen with either ibuprofen or hydroxychloroquine.3
On the basis of their real-world experience, they called for the drug to be made routinely available to patients suffering with COVID-19.
Further weight has been added to the discussion by Dr Rajan Ravichandran, a consultant nephrologist in Chennai, India. He points out that indomethacin has been used in the past to suppress the cytokine release syndrome associated with the use of OKT3 anti-rejection treatment after renal transplantation. Given that cytokine release is a feature of deteriorating COVID-19, he argues that early administration of indomethacin in patients with mild–moderate infection could prevent the hypoxaemia and probably hasten recovery of these patients. If it also reduced the viral load patients would become less contagious.4 An additional benefit of indomethacin would be its effects on coagulation and clotting in sepsis and shock,5 he says.
One modelling study has suggested that 75mg indomethacin, slow-release, twice daily (or 50mg immediate-release indomethacin three-times a day) given early in the course of the disease would maximise the antiviral and anti-inflammatory effects.6
Given that indomethacin is an old, cheap drug with which there is a wealth of experience, it is hard to avoid the conclusion that a trial of indomethacin in mild–moderate COVID-19 is urgently needed. This could easily be accomplished at present – after all, there are many more patients with mild–moderate COVID-19 than with severe, critical disease. If the duration and severity of the illness were indeed shortened, the economic benefits would be considerable. It is of interest that a randomised, controlled trial of oral indomethacin 75mg for COVID pneumonia is now recruiting in Iran.7
The use of non-steroidal anti-inflammatory agents in COVID-19 was greatly hampered by early concerns that they could be harmful, however, this has now been comprehensively rebutted.8 The recent announcement of the LIBERATE trial, in which three doses of lipid ibuprofen will be given to hypoxaemic patients, shows how far understanding has advanced here.
If we have to learn to live with this virus, as many have predicted, then it will be important to have treatments to hand that are inexpensive, non-toxic and readily available to manage future outbreaks. Other healthcare systems around the world are waking up to the possibility of repurposing indomethacin to mitigate the impact of mild–moderate COVID-19 by reducing the severity and duration of disease.
A trial of indomethacin in mild–moderate COVID-19 is now urgently needed in Europe.
References
19th June 2020
However, little known about the real-world relative safety and efficacy of different anticoagulants. In this large retrospective US study of a claims database, 25,193 patients were initiated on either warfarin (46.7%) or apixaban and with a DVT diagnosis. The clinical outcomes assessed included the risk of a major bleed, a clinically relevant non-major bleed, recurrent DVT and all-cause hospitalisation. After matching, 8858 warfarin-apixaban pairs were followed for a mean of 109 and 103 days respectively.
The use of warfarin was associated with a higher risk of a major bleed (hazard ratio, HR = 1.52), a clinically relevant non-major bleed (HR = 1.27) and recurrent DVT (HR = 1.50) compared with apixaban but there was no difference in the risk of all-cause hospitalisation.
Although not relevant to a UK setting, the authors also assessed the economic impact of the two treatments, which revealed that warfarin patients had a significantly higher all-cause medical costs ($2333 vs $1992, p = 0.001) compared with those prescribed apixaban although once pharmacy costs were included, the differences were no longer significant.
A potential limitation was that the study was funded by the manufacturer of apixaban although they do note that the findings are consistent with other available clinical trial data.
Reference
Guo JD et al. Comparative clinical and economic outcomes associated with warfarin versus apxiban in the treatment of patients with venous thromboembolism in a large US commercial claims database. J Manag Care Spec Pharm 2020; May 27.
Intranasal corticosteroids (INCs) are considered the gold standard for the management of the nasal symptoms associated with SAR but there is increasing evidence that INCs can also alleviate many of the ocular signs.
In a recent meta-analysis of studies, a group from Hackensack meridian school of medicine, Seton Hall university, New Jersey, compared the effect on ocular symptoms of two intranasal corticosteroids, triamcinolone acetonide (TAA) and fluticasone propionate (FP). They identified eight randomised double or single-blind trials that included 1727 patients which assessed the mean change in total or individual eye symptoms (that is, tearing, redness and itching).
Interestingly, none of the trials included ocular symptoms as a primary endpoint. In total, 859 patients were assigned to TAA, 327 to FP and 541 to placebo. The primary outcome was the mean change in total eye symptoms from baseline to week 2. For TAA, the mean difference in symptom reduction (compared to placebo) was -0.32 and the mean difference compared to FP was not significantly different. The authors concluded that both TAA and FP are equally effective at reducing ocular symptoms in those with SAR.
Reference
Bielory L et al. Ocular symptoms improvement from intranasal triamcinolone compared with placebo and intranasal fluticasone propionate a meta-analysis. Ann Allergy Asthma Immunol 2020;124:616-21.
Recommended treatments include emollients and intermittent use of topical corticosteroids. For those with moderate-to-severe disease and where topical therapy fails, oral immunosuppressive treatments, for example, prednisolone, ciclosporin, azathioprine and methotrexate are used and while effective, apart from methotrexate, long-term use of oral treatments is not recommended.2 The introduction of the first monoclonal antibody dupilumab, in August 2019, for patients with moderate-to-severe AE was a major treatment advance although a proportion of patients do not achieve a satisfactory response from the drug,3 hence the need for alternative and effective therapeutic options.
In recent years much interest has centred on a new-class of drugs, the Janus kinase inhibitors (JAKis) of which there are three (tofacitinib, baricitinib and upadacitinib) currently licensed for rheumatoid arthritis and psoriatic arthritis (tofacitinib only). The Janus kinase (JAK) pathway facilitates transmission of chemical signals from outside of the cell (that is, once a ligand binds to its receptor) to the nucleus and the subsequent activation of genes involved in a variety of processes such as immune cell division, activation, recruitment and in the context of AE, inflammation. The Janus family consists of four receptor-associated kinases (JAK1, JAK2, JAK3 and TYK2) and a signal transducer and activator of transcription (STAT) pathway. While the precise aetiology of AE remains to be determined, it is characterised by barrier impairment which is thought, in part due to an exaggerated T-helper 2 (Th2) cell response. Keratinocytes activate dendritic and Langerhans cells which subsequently stimulate Th2 cells to produce a range of pro-inflammatory cytokines including interleukin (IL)-4, IL-5, IL-13, IL-31 and IL-33.4 Furthermore, both IL-4 and IL-13 activate the JAK-STAT pathway, leading to the production of pro-inflammatory cytokines5 and through their action on gene expression, downregulate the production of many of the proteins essential for skin-barrier function.6 As a result, JAKis have a potentially important role in attenuating the downstream activation of many different inflammatory cytokines, hence their role in rheumatoid arthritis. However, the recent publication of the results from two Phase III trials, suggest that oral JAKis represent a potentially important new development in the management of moderate-to-severe atopic eczema.
Clinical studies
The first trial involved baricitinib, which inhibits JAK1 and JAK2. In two identical, double-blind, 16-week, Phase III trials, 1239 adults with moderate-to-severe AE who had failed to adequately respond to topical therapies, received either placebo, or 1, 2 or 4mg oral baricitinib daily.7 Emollients were allowed throughout the trial but any other oral or topical therapies were stopped but permitted as rescue treatment if required. The primary outcomes were an investigator global assessment (IGA) score of 0 (clear) or 1 (almost clear) and a > 2-point improvement from baseline in IGA score. After 16 weeks, 16.8% of patients taking baricitinib 4mg achieved the primary outcome, 11.4% (baricitinib 2mg) and 11.8% (baricitinib 1mg) compared with 4.8% in the placebo group. Baricitinib 4mg was most effective and improvements in itch, sleep disturbance and skin pain were evident after one week of treatment.
The second trial involved abrocitinib (a JAK1 inhibitor) with 391 patients, aged 12 years and over, given the drug at a daily dose of 200mg or 100mg compared with placebo for 12 weeks.8 As in the baricitinib trials, all patients had a documented inadequate response to topical corticosteroids and topical calcineurin inhibitors. The study employed the same primary outcome measures as the baricitinib trials. At the study end, 38.1% of those given abrocitinib 200mg achieved the primary outcome, 28.4% (abrocitinib 100mg) vs 9.1% in the placebo group. As with baricitinib, patients receiving abrocitinib, improvements in signs and symptoms of AE, were apparent within two weeks. Trials of a third agent, upadacitinib, which is also a JAKi, are underway.
In terms of adverse effects, these occurred in up to 58% of patients receiving baricitinib 4mg although no more than 2.5% of these, which included nasopharyngitis and upper respiratory tract infections, were considered as severe. In the abrocitinib trial, 65.8% of those given the 200mg dose experienced an adverse effect, compared to 62.7% in the lower dose group and 53.8% in those taking placebo. The most common adverse effect was nausea in the high dose groups (14.2%), followed by nasopharyngitis (7.7%).
Place in therapy
To date, the information on the efficacy of JAKis in the management of atopic eczema is promising but limited. There are several Phase II studies of other oral and topical JAKis and the results from Phase III studies of these agents are eagerly awaited. Nevertheless, there is a need for studies to assess the longer-term effectiveness of this class of drugs and if there are any important trade-offs between efficacy and safety. None of these agents are currently licensed for the use of atopic eczema and there is an FDA black box warning for the risk of severe infection with baricitinib 2mg (brand name Olumiant) when used for rheumatoid arthritis.9 It is also important to ascertain where this class might sit in the treatment hierarchy. Despite these reservations, it is likely that JAKis represent a potentially useful addition to the treatment armamentarium of doctors managing patients with atopic eczema and their introduction, once it occurs, should be welcomed.
References
16th June 2020
Over 11,500 patients have been enrolled from over 175 NHS hospitals in the UK.
On 8 June, recruitment to the dexamethasone arm was halted since, in the view of the trial Steering Committee, sufficient patients had been enrolled to establish whether or not the drug had a meaningful benefit.
A total of 2104 patients were randomised to receive dexamethasone 6 mg once per day (either by mouth or by intravenous injection) for ten days and were compared with 4321 patients randomised to usual care alone. Among the patients who received usual care alone, 28-day mortality was highest in those who required ventilation (41%), intermediate in those patients who required oxygen only (25%), and lowest among those who did not require any respiratory intervention (13%).
Dexamethasone reduced deaths by one-third in ventilated patients (rate ratio 0.65 [95% confidence interval 0.48 to 0.88]; p=0.0003) and by one fifth in other patients receiving oxygen only (0.80 [0.67 to 0.96]; p=0.0021). There was no benefit among those patients who did not require respiratory support (1.22 [0.86 to 1.75; p=0.14).
Based on these results, 1 death would be prevented by treatment of around 8 ventilated patients or around 25 patients requiring oxygen alone.
Given the public health importance of these results, we are now working to publish the full details as soon as possible.
Peter Horby, Professor of Emerging Infectious Diseases in the Nuffield Department of Medicine, University of Oxford, and one of the Chief Investigators for the trial, said: ‘Dexamethasone is the first drug to be shown to improve survival in COVID-19. This is an extremely welcome result. The survival benefit is clear and large in those patients who are sick enough to require oxygen treatment, so dexamethasone should now become standard of care in these patients. Dexamethasone is inexpensive, on the shelf, and can be used immediately to save lives worldwide.’
Martin Landray, Professor of Medicine and Epidemiology at the Nuffield Department of Population Health, University of Oxford, one of the Chief Investigators, said: ‘Since the appearance of COVID-19 six months ago, the search has been on for treatments that can improve survival, particularly in the sickest patients. These preliminary results from the RECOVERY trial are very clear – dexamethasone reduces the risk of death among patients with severe respiratory complications. COVID-19 is a global disease – it is fantastic that the first treatment demonstrated to reduce mortality is one that is instantly available and affordable worldwide.’
The UK Government’s Chief Scientific Adviser, Sir Patrick Vallance, said, ‘This is tremendous news today from the Recovery trial showing that dexamethasone is the first drug to reduce mortality from COVID-19. It is particularly exciting as this is an inexpensive widely available medicine. This is a ground-breaking development in our fight against the disease, and the speed at which researchers have progressed finding an effective treatment is truly remarkable. It shows the importance of doing high quality clinical trials and basing decisions on the results of those trials.’
Researchers from the European intergroup for childhood non-Hodgkin lymphoma and oncology group, recently published data from a Phase III, international, randomised clinical trial in patients under 18 years of age who had a high-risk, mature B-cell lymphoma (stage III) or acute leukaemia.
The trial compared the addition of six doses of rituximab to standard lymphoma malins B (LMB) chemotherapy against LMB therapy alone in 328 patients.
The primary endpoint was event-free survival which was defined in several ways including relapse, progressive disease, second cancer or death from any cause. After a median follow-up of 39.9 months, there were ten events in the rituximab group compared with 28 in the LMB group and the event-free survival rate was 93.9% in patients given rituximab compared to 82.3% in the LMB group. In total, eight patients treated with rituximab died compared with 20 in the LMB group.
However, although more effective, treatment with rituximab resulted in 37.7% of patients experiencing serious adverse effects, mainly febrile neutropenia, compared with 32.7% in the LMB group.
Reference
Minard-Colin V et al. Rituximab for high-risk, mature B-cell non-Hodgkin’s lymphoma in children. N Engl J Med 2020;382:2207-19.
In a new study, a team from the department of civil, environmental and geomatic engineering, University of London, found that when they inoculated a bed hand rail in an isolation room with a sample of viral DNA (which was not harmful to humans), it was found to have spread within 10 hours to 41% of all surfaces sampled within the ward including other beds and clinical areas of the ward.
In fact, 86% of clinical areas sampled tested positive for the virus and more worryingly, the viral DNA persisted so that after 5 days, 41% of sampled sites were still positive. The team noted that in the current pandemic close attention to cleaning was paramount and whilst the virus used in the study was not harmful, it clearly indicated a failure of hygiene measures, in particular hand washing, which is known to remove the test virus. The apparent failure of adequate hygiene measures was of greater concern given that the sample virus was inoculated in an isolation room.
Although the study did not use COVID-19, it clearly showed how lack of attention to hygiene provided a potential route for transmission of a virus, emphasising the importance of cleaning surfaces.
Reference
Rawlinson S, Ciric E, Cloutman-Green. COVID-19 pandemic – let’s not forget surfaces. [Letter] J Hosp Infect 2020; DOI: 10.1016/j.jhin.2020.05.022
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