EFIC COVID-19 Task Force

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Type of article: Commentary

Level of evidence: 5 (Expert opinion without explicit critical appraisal or based on physiology bench research or first principles)

Results: This commentary retraces the origins of the worldwide alarm towards the use of ibuprofen, starting with a tweet from the French Health Minister who, after 4 young people reportedly developed serious COVID-19 disease after taking NSAIDs, advised that ibuprofen could aggravate the infection. The report, although unpublished, was reported in The BMJ and endorsed by specialists from France and UK, and by the WHO.

The authors criticise the low level of evidence of these reports, as well as the notion, published in The Lancet, that ibuprofen could enhance coronavirus infectivity by increasing the bioavailability of angiotensin converter enzyme (ACE), to which the virus binds. They argue that drawing conclusions from theoretical pharmacology is dangerous and can lead to erroneous results, such as the hypothesis that co-administration of ibuprofen and aspirin could counteract antiplatelet effectiveness, which was based on pharmacological thromboxane levels but then refuted in a randomized controlled trial.

Implications: Rather than concluding that ibuprofen is safe for COVID-19 related fever, the authors observe that current epidemiologic evidence “is not strong enough to infer a causal link of a harmful effect of ibuprofen in COVID-19”. They advise, however, that patients with COVID-19 take acetaminophen monotherapy for fever reduction.

Commentary: A very interesting critique of the multiple biases and insufficiencies that have polluted medical literature on this topic. It is, however, amusing that after such a clear analysis the authors end up recommending the same approach –paracetamol (acetaminophen) – as the French Minister in his initial tweet.

Reviewed by EFIC on April 23, 2020 – read the article in full here.

Type of study: Letter to editor

Level of evidence: 5 (Expert opinion without critical opinion or based on physiology bench research or first principles)

Results: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been identified as the pathogen of COVID-19. The spike protein on this virus binds the angiotensin-converting enzyme 2 (ACE2) receptor, mediating entry into human cells. Studies have also detected SARS-CoV-2 in the cerebrospinal fluid of infected patients. Although the expression of ACE2 receptor in the human nervous system has not been fully identified, ACE2 has been detected in neurons and microglia in the spinal dorsal horn of mice.

The study suggests that SARS-CoV-2 might infect ACE2-positive cells in human spinal dorsal horn and decrease functional ACE2 activity resulting in the accumulation of angiotensin-II and decrease of angiotensin (1-7). Consequently, SARS-CoV-2 infection in the spinal cord may induce pain.

Implications: The potential burden of pain induced by COVID-19 cannot be ignored. However, the role of the ACE2 receptor in pain transmission and pain management for people infected with SARS-CoV-2 needs further scientific and clinical studies, in order to guide treatment and public health policy.

Commentary: There is no definitive evidence yet on the importance of this mechanism in humans, but a scientifically sound hypothesis is proposed. Yet, we should be cautious when drawing conclusions from mechanistic or theoretical pharmacology, especially from rodents, as a number of examples show that such evidence can later be refuted by clinical data.

Reviewed by EFIC on May 15, 2020 – read the full article here

Moore N, Carleton B, Blin P, Bosco-Levy P, Droz C. Drug Saf. 2020 Jul;43(7):611-614. doi: 10.1007/s40264-020-00953-0. No abstract available.PMID: 32529474 [PubMed – indexed for MEDLINE] Free PMC Article

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Type of study: Review

Level of evidence: 3A (less systematic review of a variety of study designs, including in-vitro, in-vivo, animal and human-studies.)

Population: People with osteoarthritis

Results: NSAIDs: No evidence for discontinuation

Corticosteroids: No evidence for discontinuation of systemic treatment

Opioids: No evidence for discontinuation – the authors recommend weak opioids with no immunosuppressive activity

Monoclonal Antibodies (mAbs): No evidence for experimental use of mAbs in OA and COVID-19 patients except compassionate use or within clinical trials

Commentary: This paper does not add new findings to the existing literature but offers a good one-stop review for the specific care of patients with osteoarthritis. Overall, therapies for osteoarthritis appear to be safe and there is not any clear indication to avoid prescription or suggest discontinuation of existing pharmacological therapies due to COVID-19 infection or its complications.

The authors preference for weak opioids without immunosuppressive activity is subjective opinion and may be dose-related. High dose weak opioid may have similar effects as low dose strong opioids. Although different opioids vary in their effects on the immune system, any clinical relevance is still uncertain.

The authors acknowledge that decisions need to be scrutinized in the high inflammatory stage of COVID-19 infection.

Reviewed by EFIC on May 20, 2020 – Read the full article here

Type of study: Views and perspectives

Level of evidence: 2A (systematic review of cohort studies)

Results: Initial reported symptoms of SARS‐CoV‐2 infection were mainly respiratory, and were characterised by fever, sore throat, cough, and dyspnoea. Other symptoms, including headache, abdominal pain, diarrhoea, loss of taste and smell, have been added as possible symptoms of COVID-19 over time. Reports of neurological symptoms are increasing rapidly, and headache appears to be most common. Headache has been reported in 11%-34% of hospitalized COVID-19 patients, however clinical features of these headaches are not reported. The authors experience suggest significant features of headache presentation in symptomatic COVID-19 patients were new-onset, moderate-severe, bilateral headache with pulsating or pressing quality in the temporoparietal, forehead or periorbital region. The most striking features of the headache were variable onset and poor response to common analgesics, or high relapse rate, that was limited to the active phase of the COVID-19.

Implications: As a common non-respiratory symptom of COVID-19, headache should not be overlooked, and its characteristics should be recorded with scrutiny. If headache is ignored as a symptom of COVID-19, there may be delay in diagnosis, leading to further infection cases in the community.

Commentary: Clinical features of headache related have to COVID-19 have not been well documented. A case vignette is described and several possible pathophysiological mechanisms are proposed from theoretical considerations.

Reviewed by EFIC on May 20, 2020 – Read the full article here

Type of study: Mini-review and theoretical model of optimal dosage

Population: in vitro studies; in vivo animal studies

Results: Indometacin, an anti-inflammatory drug, has been used as symptomatic treatment to improve oxygenation in patients with acute respiratory distress [Hanly et al Lancet 1987; Steinberg et al Circ Shock 1990] and to reduce proinflammatory interleukin-6 levels [Sacerdote et al Inflamm Res 1995]. In addition, indometacin has been shown to have potent in-vitro antiviral properties against human SARS-CoV-1, canine CCoV, and more recently on human SARS CoV-2 [Amici et al Antivir Ther. 2006, Xu et al Front Med J. 2020].

In this paper the authors propose indometacin as a promising candidate for the treatment of SARS-CoV-2 and try to provide criteria for comparing benefits of alternative dosage regimens using a model-based approach. They characterize % of recovery and viral load in CCoV-infected dogs, to estimate the PK of indometacin in dog and human using published data after administration of immediate (IR) and sustained-release (SR) formulations, and to estimate the expected antiviral activity as a function of different assumptions on the effective exposure in human.

Implications: Should indometacin prove active against SARS CoV-2 in humans, the best theoretical dosing regimens modelled were 50 mg three-times-a-day for the IR formulation, and 75 mg twice-a-day for the SR formulation.

Commentary: The main interest of this paper is in the reference list, which provides published data on the efficacy of Indometacin on various coronaviruses including COVID-1 and COVID-2, in vitro, in dogs, and potentially in humans. Should current clinical trial using indometacin (that started April 2020) be positive, this study provides a PK/PD basis to determine best therapeutic regimens. Of particular note, indomethacin has a higher toxicity index than other NSAIDs, including ibuprofen (especially GI related) and the recommended dosing is relatively high. So, a gastroprotective drug should be indicated also.

Reviewed by EFIC on May 28, 2020 – read the full article here

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Type of article: Commentary, brief literature analysis

Level of evidence: 5 (Expert opinion without explicit critical appraisal or based on physiology bench research or first principles)

Population: Patients suffering chronic headache and treated with ACE inhibitors (ACE-I), angiotensin II receptor blockers (ARB) or ibuprofen

Results: Concern has arisen in view of a putative link between the use of inhibitors of the renin-angiotensin system (ACE-I, ARB) and ibuprofen and an increased risk for COVID-19 infection. The authors discuss this concern in relation to headache treatment and conclude that, based on current evidence, there is no reason to abandon treatment with ACEI, ARB or ibuprofen in people with headache. There is no convincing evidence in medical / research literature that either renin-angiotensin system blockers or ibuprofen worsen SARS-CoV-2 infection in any type of patient, including headache patients.

Implications: The authors, in agreement with the advice of international cardiovascular societies, see no rationale to alter the prescription of these drugs that have an important role in the treatment of headache.

Commentary: There is no reason, empirical or scientific, to discontinue a treatment with ACE-I/ARB or ibuprofen in patients with COVID-19 infection. Discussion on mechanisms is short but sensible and rich. Conclusions are in line with recent results from Zhang et al (Circ. Res 2020, doi: 10.1161/CIRCRESAHA.120.317134.), that shows absence of complications and even better outcome in hypertensive patients with Covid19 treated with ACE-I/ARB.

Reviewed by EFIC on May 15, 2020 – read the full article here.

Type of study: Review

Level of evidence: 3A (systematic review of a variety of study types including in-vitro-, case-, in-vivo, animal- and human studies).

Results: NSAIDs: The search did not identify any strong evidence for or against the use of ibuprofen for treatment of COVID-19 specifically.

Corticosteroids: Some evidence that corticosteroids may be beneficial in the treatment of SARS-CoV. However, this is not specific to COVID-19.

Commentary: There is no definitive evidence that NSAIDs or corticosteroids are contraindicated in COVID-19.

Reviewed by EFIC on April 23, 2020 – read the full article here.

Type of study: Letter to the Editor

Level of evidence: 5 (Expert opinion without explicit critical appraisal or based on physiology bench research or first principles)

Results: During the COVID-19 pandemic, many patients may look for natural remedies to protect themselves. Use of products containing cannabinoids have proliferated amidst claims of health benefits including immune “support” or “boosting”. Cannabidiol (CBD) and tetrahydrocannabinol (THC) have complex pharmacological properties, including anti-inflammatory effects, that may be useful in certain conditions (including autoimmune and neurodegeneration diseases). However, they suppress cytokines, chemokines, effector T-cells, and microglial cells, reducing the host response to pathogens including viruses like SARS-CoV-2.

Implications: Current pharmacological and clinical evidence suggest CBD and THC decrease the body’s ability to fight infections, in particular viral and respiratory infections. In a clinical trial of cannabidiol for epilepsy, respiratory infections (pneumonia) were over 30% more common in those receiving CBD versus placebo. The author recommends avoiding the use of cannabinoids during this pandemic unless medically supported for recognised indications (e.g. seizures, cancer, chronic pain), and highlights false marketing claims of medical benefit including “immune system boosting” or antiviral effects, that should be reported to regulatory bodies.

Commentary: A very concise yet well-documented summary of the potentially serious problems of health-marketing as applied to cannabis. The analysis is USA-centred, where the direct advertisement and marketing of medicines is greater than in Europe.

Reviewed by EFIC on April 23, 2020 – read the full article here.

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Type of study: Case reports

Level of evidence: 4 (Case studies)

Population: Two people with COVID-19 presenting with abdominal pain

Results:
Case 1:

• Male, 73 years old, hypertension, end-stage renal disease and haemodialysis

• Presented with fever, cough, dyspnoea, bleeding diarrhoea

• Developed acute left lower quadrant abdominal pain with red bright rectal bleeding

• PCR positive for SARS-CoV-2

• Anaemia, leucopoenia, lymphopenia

• D-dimer level 4226.0 ng/ml; increased ferritin CRP, procalcitonin

• Thoracic X-rays demonstrated bilateral opacities and abdominal CT-scan suggested ischaemic colitis. Anticoagulant prescribed

• Stable for 5 days, then cardiac arrest and death

Case 2:

• Female, 61 years old, with a history of type II diabetes mellitus

• Three-day history of dry cough and non-radiating abdominal pain for one day

• Sharp, severe, periumbilical pain which began acutely that morning

• Positive for SARS-CoV-2

• Pulmonary angiography CT-scan showed thromboembolism in thoracic + abdominal aorta. D-dimer 8264 ng/ml (>16 times normal)

• Clinically significant venous and arterial that required tissue plasminogen activator

Implications: COVID-19 associated coagulopathy can include thromboembolism and may present with abdominal pain or pulmonary embolism. In patients with alerting symptoms, increased D-dimer levels should prompt appropriate investigation to detect thrombosis.

Commentary: These are examples of COVID-19 presenting with abdominal pain as presenting symptom. COVID-19 associated coagulopathy can worsen prognosis, because of undetected intestinal ischaemia. D-Dimer is an important investigation if suspect coagulopathy in these patients.

Other cases of COVID-19 related acute-pseudo-surgical abdomen have been reported including;
Ahmed AOE, Badawi M, Ahmed K, Mohamed MFH. COVID-19 Masquerading as an Acute Surgical Abdomen. Am J Trop Med Hyg. 2020 Jun 9.

doi: 10.4269/ajtmh.20-0559. [Epub ahead of print]

Reviewed by EFIC on June 5, 2020 – Read the full article here

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Type of study: Online survey of rheumatology patients

Level of evidence: Level 4 (Case series or poor quality cohort or case-control study)

Population: Rheumatological patients at a large tertiary hospital in Australia

Methodological approach: People were invited to complete a survey that assessed their concerns regarding risks conferred by their rheumatological condition or medications, impact of receiving information about on the likelihood of continuing medication during the COVID-19 pandemic, and acceptance of telehealth.

Results: The response rate was 21% (550/2630 people). Most people (63.8%) were prescribed more than one conventional synthetic disease-modifying antirheumatic drug and 17.8% were prescribed a biologic or targeted synthetic anti-rheumatic drug. Prednisolone and non-steroidal anti-inflammatory drugs (NSAIDs) use was reported by 26.7% and 22.4% of people, respectively.

41% of people were concerned that their rheumatological disease increased their risk of COVID-19 infection and severity of infection (52.3%). More people were concerned that their medications increased their risk of COVID-19 infection (55.7%), while 76.1% were concerned that medications increased the severity of infection.

Most people (61%) had been provided with information about the impact of COVID-19 on rheumatological conditions. Telehealth was considered appropriate to almost all people (98.4%) during the pandemic.

Commentary: This article exemplifies concerns that either rheumatological conditions and/or their medication might increase the risk for COVID-19 and its severity. Understandably some people may consider stopping their medicines and run the risk of subsequent complications or worsening of their underlying disease.

Reviewed by EFIC on June 12, 2020 – Read the full article here

Type of study: retrospective analysis of 101 medical and nursing case notes by clinician-researchers

Level of evidence: Level 4 (case series)

Results: Of the 101 patients with COVID-19 infection referred for end-of-life palliative care 64 were males and 37 females with a median age of 82 [72-89]. The most prevalent symptoms were in descendent order breathlessness, agitation, drowsiness, pain, and delirium. Apart from non-pharmacological treatment, patients received mainly symptom-relieving drugs with a median final dose of 10 mg/24 h morphine and 10 mg/24 h midazolam. Patients spent a median of 2 [1–4] days under the palliative care team and received 3 [2–5] contacts. 75 patients died, 13 were discharged and 13 remained under palliative inpatient care.

Implications: This retrospective analysis of a case series of COVID-19 patients receiving end-of-life palliative care instead of a referral to an intensive care ward gives some interesting insights into the course of the disease, the main symptoms under which the patients suffer, the required treatment measures, and their effectiveness.

Commentary: Intriguing is the information on end-of-life palliative care patients with COVID-19 infection in comparison to the intensive care patients that receive much more media attention. However, it provides little new information for the commonly known palliative care. The therapies that were initiated belong to the standard of care.

Reviewed by EFIC on April 30, 2020 – read the full article here.

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Type of study: Survey

Level of evidence: 2C (Ecological study)

Population: Patients awaiting elective hip and knee arthroplasty

Intervention: A survey (electronically or over the phone) to patients awaiting hip or knee replacement to assess pain, anxiety, physical function and economic capacity to undergo a delayed surgery.

Results: Hospitals in the United States – similar to hospitals in many other countries– stopped performing elective procedures when COVID-19 was declared a pandemic. This led to the deferral of a large number of hip and knee arthroplasties between March and July 2020 and increasing waiting times. Six institutions distributed the survey and 360 patients responded.

Most patients were anxious about the uncertainty of when their deferred surgery would take place. While 85% of the sample agreed with the surgery deferral in line with public health advice, 90% planned to reschedule their surgery as soon as possible. Patients in North East States were most concerned with contracting COVID-19 during their hospital admission. Younger patients were more anxious about the financial situation and job security and its impact on being able to afford the cost of the future surgery.

Implications: The COVID-19 pandemic has a significant impact on patients with hip and knee osteoarthritis who have to wait in uncertainty until their surgery is rescheduled. Supporting individuals during this time with managing pain is very important in terms of both physical and emotional wellbeing.

Commentary: This small survey offers an insight into the impact that COVID-19 is having on patients with knee and hip osteoarthritis who require surgery. The result that 90% of the sample will reschedule their surgery as soon as possible is interesting in light of debate on social media that COVID-19 might lead to a reduction in the number of musculoskeletal pain procedures. A limitation of this study is that it does not reveal how many individuals received the survey, so we are unable to assess the response rate.

Reviewed by EFIC on August 11, 2020 – Read the full article here

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Type of study: Case series

Level of evidence: 4 (Case series)

Population: Patients with COVID-19 presenting with neurological syndromes

Results: Clinical and paraclinical data collected from 43 consecutive cases with COVID-19 confirmed through RNA PCR, or with probable/possible disease according to World Health Organization criteria, and presenting with neurological symptoms. Five major categories are described:

• (i) encephalopathies (n= 10) with delirium/psychosis and no distinct MRI or CSF abnormalities, with 9 patients making a full or partial recovery with supportive care only;
• (ii) inflammatory CNS syndromes (n= 12) including encephalitis, acute disseminated encephalomyelitis, and isolated myelitis. Of these, 10 were treated with corticosteroids, and one patient died;
• (iii) ischaemic strokes (n= 8) associated with a pro-thrombotic state (four with pulmonary thromboembolism), one of whom died;
• (iv) peripheral neurological disorders (n= 8), seven with Guillain-Barré syndrome, one with brachial plexopathy, six making an ongoing recovery; and
• (v) miscellaneous central disorders (n=5) who did not fit the categories above.

Implications: Such syndromes have similarities to those described in the other coronavirus epidemics (severe acute respiratory syndrome (SARS) in 2003, and Middle East acute respiratory syndrome (MERS) in 2012). However, overall numbers of infected individuals were much smaller, and neurological presentations were few in comparison with those being recognized in the current pandemic.

Commentary: This is probably the most detailed clinical report on the nature of neurological syndromes associated with COVID-19. To be contrasted with the previous report from the Strasbourg group (Helms et al NEJM 2020) who described essentially encephalopathy with agitation, confusion and corticospinal tract signs in 64 patients, as well other less comprehensive reports (Guan et al. NEJM 2020; Mao et al. JAMA Neurol 2020; Varatharaj et al., Lancet Psych 2020).

Reviewed by EFIC on August 11, 2020 – Read the full article here

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Type of article: Case reports from physicians about managing pain during the COVID-19 pandemic

Level of evidence: 5 (Expert opinion without critical appraisal or based on physiology bench research or first principles

Results: Most medical services In Wuhan not directly involved in intensive care, including pain management services, were partially or completely shut down. This posed challenges for clinicians and people with chronic pain. The pain medicine department found that widespread pain can be an early symptom of COVID-19 infection.

On the other hand, an increasing concern is that the concern of missing other urgent medical conditions or diagnoses when focusing on assessing for COVID-19 infection. A case of thoracic spinal neuratoma left undiagnosed due to similarities in presentation to COVID-19 infection is reported. The pandemic provided clinicians an opportunity to incorporate telemedicine into pain management for the first time due to the urgent need to provide healthcare services remotely. Clinicians need to consider strategies to encourage people with health issues needing management to seek outpatient care as many are still understandably wary of seeking in-person health care. We may prepare ourselves to see more patients who previously had COVID-19 infection visiting pain clinic as the epidemic slows.

Commentary: As well as clinical research, personal experiences in the pandemic are be important to share too. The included case reports illustrate how the combination of chronic pain and COVID-19 infection can challenge diagnosis and treatment.

Beneficial strategies for managing pain during the COVID-19 pandemic are reported and recommendations based on lessons learned in the pain medicine departments of Wuhan and Shenzhen hospitals are discussed.

Reviewed by EFIC on May 8, 2020 – read the full article here.

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Type of study: Cohort study

Level of evidence: 2B (individual cohort study)

Population: All Danish residents who tested positive for the infectious agent of COVID-19. A total of 9,236 SARS-CoV-2 PCR-positive individuals were eligible for inclusion.

Intervention: Users of NSAIDs (248 (2.7%) had filled a prescription for NSAIDs)

Comparison: Non-users of NSAIDs

Results: Treatment with NSAIDs was not associated with 30-day mortality, risk of hospitalization, ICU admission, mechanical ventilation or renal replacement therapy.

Implications: Use of Danish registries allowed for identification of all individuals who had been tested for SARS-CoV-2 in Denmark and allowed for obtaining data on prescription drug use, medical history, migration, hospital admissions, and death through individual-level linkage between health and administrative registries. The main limitations of the study are possible exposure misclassification, as not all individuals who fill an NSAID prescription use the drug continuously, and possible residual confounding by indication, as NSAIDs may generally be prescribed to healthier individuals due to their side effects, but on the other hand may also be prescribed for early symptoms of severe COVID-19.

Considering the available evidence, there is no reason to withdraw well-indicated use of NSAIDs during the SARS-CoV-2 pandemic. However, the well-established adverse effects of NSAIDs, particularly their renal, gastrointestinal, and cardiovascular effects, should always be considered, and NSAIDs should be used in the lowest possible dose for the shortest possible duration for all patients.

Commentary: This is a large cohort study demonstrating that NSAIDs do not lead to more severe coronavirus disease. This is an important finding as different theories on the use of NSAIDs were proposed during the early phases of the COVID-19 pandemic where concerns were raised that NSAIDs may lead to a more severe course of coronavirus disease.

Reviewed by EFIC on September 21, 2020 – Read the full article here

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Type of study: Review article

Level of evidence: 5 (Narrative systematic review)

Results: Management strategies identified include exercise, proper nutrition, physical therapy, and use of corrective and assistive orthotics.

Telehealth methods may be considered to deliver self-management advice to patients with knee osteoarthritis who had their surgery deferred. Home exercise programmes consisting of a combination of aerobic, resistance, and flexibility work should be considered.

Where patients with knee osteoarthritis have co-morbid obesity, a combined exercise, and diet approach to encourage weight loss can be considered.

The role of knee braces, sleeves, foot orthoses, footwear, walking aids and heat is uncertain in terms of pain, disability, and quality of life.

Commentary: This review article provides an overview of the non-pharmacological options for the home management of knee osteoarthritis. Exercise and virtual education appear to be the most promising interventions with the strongest supporting evidence. However, the review article lacks a risk of bias assessment and pooled analyses and so the true effectiveness of any of the proposed strategies remains uncertain.

Reviewed by EFIC on August 11, 2020 – Read the full article here

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Type of study: Review

Level of evidence: 5 (Expert opinion without critical opinion or based on physiology bench research or first principles)

Results: There remains no scientific evidence establishing a clear link between renin-angiotensin system (RAS) blockers (including angiotensin receptor blockers (ARBs), angiotensin converting enzyme inhibitors ACE-I), or non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen and the worsening of COVID-19. In contrast, experimental data support the idea that ACE-2 not only serves as an entry receptor for SARS-CoV-2 but also protects the lungs from acute injury, and hence may therefore be beneficial in COVID-19 infection.

Implications: The authors propose that effective treatment with RAS blockers should not be discontinued or switched. There is insufficient evidence to recommend patients who take ibuprofen for medically indicated reasons to change their anti-inflammatory medicine in light of the COVID-19 pandemic. The choice of drug to treat COVID-19-associated fever or pain should be based on a benefit-risk assessment considering known side effects (e.g. kidney damage, gastrointestinal ulceration).

Commentary: The hypothetical risk of worsening COVID-19 does not justify discontinuing or switching RAS blockers or ibuprofen. Changes to treatment should be made in the light of benefit-risk assessment of these drugs for individuals.

Reviewed by EFIC on May 20, 2020 – Read the full article here

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Type of article: Letter to the Editor

Population: Patients with cancer pain from bone metastases

Intervention: Radiotherapy for painful bone metastases

Results: Bone metastases are a common complication of advanced cancer that cause spinal cord compression, life-threatening electrolyte imbalances, pathologic fracture and severe pain. Stepwise treatments are opioids/NSAIDs, bisphosphonates, chemo & hormone-therapy, radiation and surgery. Palliative radiotherapy for painful uncomplicated bone metastases yields significant palliation for approximately 70% of people and complete pain relief for 10-35%. In previous RCTs, both single fraction and multiple fraction radiation therapy were efficacious for pain in bone metastases, multiple fraction are better only for patients with complicated metastases, neuropathic pain or cord compression.

In the context of the current COVID-19 epidemic, this choice must be weighted with the infection risks cancer patients due to a compromised immune system. In patients with cord compression and poor survival prognosis, a single fraction of 8 Gy was found as effective as multifractionated regimens while minimizing multiple treatment visits.

Implications: In order to minimize the exposure of people with bone metastases to COVID-19 without compromising oncological outcome, the choice of a palliative radiotherapy with 8 Gy in one single fraction may be the most reasonable, with good efficacy and reduced length of patients’ exposure to hospital environment and contagion.

Commentary: The National Institute for Health and Care Excellence (NICE) in the UK recommended using radiotherapy “only if unavoidable” (Mahase E BMJ. 2020 Apr 1;369:m1338.). In the light of literature, this report recommends the use of single fraction 8 Gy radiotherapy instead of longer schedules as a safer and reasonable procedure for painful bone metastases refractory to pain medication or with spinal cord compression, during the COVID-19 epidemic.

Of particular note, the risks and benefits of radiotherapy should always be discussed with patients and staff, and adequate preventive and protective measures provided to patients and radiotherapy technicians. Radiation treatment room and nearby areas should be sanitized during treatment intervals, and the time patients spend in the waiting room minimised. A dedicated path for cancer patients separated from other hospital patients should be assured.

Reviewed by EFIC on May 20, 2020 – read the full article here

Type of study: Narrative review

Level of evidence: 5 (Expert opinion without explicit critical appraisal or based on physiology bench research or first principles)

Results: This consensus provides a good overview on safety precautions to reduce risks of infection with SARS-CoV-2 for clinicians working in pain management and the patients they treat. Other issues considered include patient flow issues and staffing plans, telemedicine options, triaging recommendations and resource utilization, and impacts on mental health of both patients and healthcare workers. Guidance on the prescription of opioids and use of steroids for interventions is provided

Commentary: The paper summarises the opinions of an expert panel that included pain management experts from the military, Veterans Health Administration, and academia in the US. Hence, the recommendations reflect current practices in the US and may not be directly applicable in other settings.

Reviewed by EFIC on April 30, 2020 – read the full article here.

Type of study: Practice recommendations to help with the care of chronic pain patients during the COVID-19 pandemic.

Level of evidence: 5 (Expert opinion without explicit critical appraisal or based on physiology bench research or first principles).

Results: Consensus recommendations on a range of topics including:

• face to face consultations (not recommended)
• telemedicine (recommended providing fits with legislative regulations)
• biopsychosocial management (recommended if social distancing can be maintained or using remote consultations)
• maintain regular review of patients prescribed opioids and that all patients receive their prescription of opioids to avoid withdrawal; and
• patients may continue prescribed NSAIDs for pain relief.

Commentary: The paper gives an overview of the expert opinion of a panel. However, the size of panel not stated. While the quality low, evidence in the paper may provide a benchmark for comparison to any local practice.

Reviewed by EFIC on April 30, 2020 – read the full article here.

Type of study: A rapid systematic literature review of published case studies, cross-sectional studies, cohort studies, and intervention studies

Level of evidence: Level 3A (Systematic review of case-control studies)

Results: Out of 2207 identified studies, 36 underwent full-text review, and 10 studies were finally selected for analysis.

To guide hospices and palliative care teams they should focus on:

• maintaining the ability to respond rapidly and flexibly;
• ensuring protocols for symptom management and psychological support, and non-specialists are trained in their use;
• being involved in triage;
• considering shifting resources from inpatient to community settings;
• considering redeploying volunteers to provide psychosocial care;
• facilitating camaraderie among staff and adopting measures to deal with stress;
• using technology to communicate with patients and carers; and
• adopting standardised data collection systems to inform operational changes and improve care.

Implications: Palliative care teams need to be flexible and rapidly redeploy resources in the face of changing needs during a pandemic, such as COVID-19. Particular attention should be to the triage of patients, palliative care expertise staff, workload and stress, anticipatory allocation of space and equipment, and standardised documentation of data.

Commentary: This rapid review provides guidance for hospices and palliative care teams to ensure that they do not become overwhelmed by rapid developments of a pandemic. There was limited detail about how studies were selected for undergoing full-text review. In addition, there was only limited evidence and a lack of quantitative data, no assessment of quality of studies, and no grading of recommendations. The use of a developed palliative care surge plan might have been used as a filter for the selection of studies. Despite these limitations, this paper gives a valuable review of literature relevant for palliative care and provides important guidance.

Reviewed by EFIC on April 30, 2020 – read the full text here.

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Type of study: Masterclass / non-systematic overview

Level of evidence: 5 (Expert opinion)

Results: Telehealth is defined as the ‘delivery of healthcare at a distance using information and communication technology’. Published systematic reviews shows that delivering interventions via telehealth methods yield similar effects on pain and disability as face to face interventions in patients with low back pain and hip/knee osteoarthritis. This is based on low certainty evidence and higher-quality trials are required.

A systematic review [Mani S et al. J Telemed Telecare 2017; 23(3): 379–391] found that telehealth assessments have good concurrent validity for pain, swelling, range of motion, muscle strength, balance, gait and functional assessment. However, only low to moderate concurrent validity was demonstrated for special orthopaedic tests, neurodynamic tests, and lumbar posture.

There is high satisfaction with telehealth interventions among individuals with musculoskeletal conditions. Patient barriers to engaging with telehealth include computer literacy, older age, lower education levels, and lack of trust in the clinician. Physiotherapist barriers to engaging with telehealth include unwillingness to change current clinical practice, low confidence with technology, and concerns over safety and patient privacy.

When choosing a telehealth platform, physiotherapists should consider components needed for their assessment (e.g. range of motion features), national privacy and security regulation for the transfer and storage of patient information, usability for the patient, cost, functionality (can be used across different browsers and has multiple features including appointment scheduling).

Implications: Telehealth seems a useful alternative to face to face consultations and interventions in terms of effectiveness for treating musculoskeletal pain conditions.

Commentary: This paper provides a useful overview of the current evidence base for the effectiveness of telehealth interventions for the treatment of pain and disability among patients with musculoskeletal conditions. The paper highlights the results of published systematic reviews showing that telehealth interventions provide similar effects to face to face rehabilitation.

The authors specifically mention the limitations in the evidence base and call for the conduct of high-quality trials before any definitive conclusions can be drawn. The paper outlines very practical tips for picking a telehealth platform and implementing telehealth in physiotherapy practice.

Reviewed by EFIC on August 11, 2020 – Read the full article here

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