Does CEUS offer greater diagnostic accuracy for abdominal trauma than conventional ultrasound?

9th February 2023

Contrast enhanced ultrasound has greater diagnostic accuracy for abdominal trauma than conventional ultrasound in emergency care settings

The use of contrast enhanced (CE) ultrasound for patients with abdominal trauma prior to computed tomography imaging has a higher diagnostic accuracy in comparison to conventional ultrasound according to the results of a systematic review and meta-analysis by researchers from the Brookdale University Hospital and Medical Center, New York, US.

Undertaking an extended Focused Assessment with Sonography in Trauma (eFAST) is commonly performed as part of the initial assessment of patients who have experienced trauma. Moreover, a systematic review has shown how eFAST serves as a useful bedside tool which is able to rule-in pneumothorax, pericardial effusion as well as intra-abdominal free fluid within a trauma setting but is less useful as a rule-out tool. The diagnostic capability of ultrasound can be improved with the use of a contrast media. In fact, contrast enhanced ultrasound in children has been found to have a comparable performance to both CT and MRI with a very high degree of specificity and hence has the potential to reduce irradiation exposure in paediatric patients. It has also been shown that contrast enhanced ultrasound seems to be both safe and accurate for the identification of abdominal solid organ injuries in children who have experienced a blunt abdominal trauma. Nevertheless, the comparative accuracy of CE ultrasound has not been directly compared to eFAST during the initial trauma assessment and was the subject of the review by the US researchers. The team focused on the use of both ultrasound methods for the initial assessment of patients with abdominal trauma before CT imaging. Paired pooled sensitivity and specificity were used to assess the relative merits of both approaches.

Contrast enhanced ultrasound diagnostic value in abdominal trauma

Following a literature search, a total of 10 eligible studies with 1,359 patients and 30 pairwise comparisons were included in the analysis.

Overall, the paired, pooled sensitivity for CE ultrasound was 0.933 (95% CI 0.917 – 0.948) compared to 0.559 (95% CI 0.527 – 0.591) for conventional ultrasound (p < 0.001). The pooled specificity was also significantly higher (0.995 vs 0.975, p < 0.001). In fact, in sub-group analysis, CE ultrasound was superior to conventional ultrasound for all other areas including the liver, kidneys and adrenals, spleen and for the presence of active bleeding.

Based on these findings, the authors concluded that CE ultrasound was a superior method for differentiating abdominal trauma injuries when used as an initial means of assessment in emergency departments.

Citation
Sutarjono B et al. Is it time to re-think FAST? A systematic review and meta-analysis of Contrast-Enhanced Ultrasound (CEUS) and conventional ultrasound for initial assessment of abdominal trauma. BMC Emerg Med 2023

Review suggests antidepressants of limited efficacy in chronic pain

8th February 2023

Antidepressant efficacy in the management of chronic pain conditions appears to be limited according to an overview of systematic reviews

An overview of systematic reviews by researchers from Australia and the UK which examined the use of an antidepressant for the management of a range of chronic pain conditions, has concluded that the evidence of efficacy for all classes of drugs was moderate to low.

The presence of chronic pain is a common condition with one US survey finding that 50.2 million adults reported experiencing pain on most days or every day. Although both opioids and non-steroidal anti-inflammatory agents can be used to treat chronic pain, guidance from NICE in the UK, advises that the pharmacological management of such pain should involve the use of an antidepressant and which should be either amitriptyline, citalopram, duloxetine, fluoxetine, paroxetine or sertraline. But exactly how effective are antidepressant drugs for the management of chronic pain was the subject of the recent review by the Australian and UK researchers. The team undertook an overview of all available systematic reviews describing the use of an antidepressant (compared to placebo) for the management of any chronic painful condition in adults. The researchers set their primary outcome as pain and which could be measured with any instrument. The pain outcomes were then converted to a 0 to 100 scale and for which 0 represented no pain and 100, worst pain.

Antidepressant use and pain outcomes

A total of 26 studies with over 25,000 participants were included in the final analysis and which covered 22 distinct pain conditions and 42 antidepressants (8 different classes) versus placebo comparisons.

Overall, none of the reviews provided high certainty evidence on the efficacy of an antidepressant for pain in the management of any of the conditions examined. There were 11 comparisons of 9 different conditions where antidepressants were effective, largely serotonin-norepinephrine (noradrenaline) re-uptake inhibitors. This latter class was effective (mainly duloxetine) for back pain, postoperative pain, neuropathic pain and fibromyalgia. In the other cases, the antidepressants were deemed to be either ineffective or the evidence was inconclusive.

Interestingly, the researchers found that 74% of tricyclic antidepressant prescriptions were for a pain condition yet of 14 pain problems examined, this class of drugs were only effective for three conditions (irritable bowel syndrome, neuropathic pain and chronic tension-type headache). However, the certainty of the evidence was low in each case.

The authors concluded that overall, the efficacy of antidepressants was found in only 11 of the 42 comparisons and suggested that a more nuanced approach was needed when using these drugs for a painful condition.

Citation
Ferreira GE et al. Efficacy, safety, and tolerability of antidepressants for pain in adults: overview of systematic reviews. BMJ 2023

Skeletal muscle reduces nearly 2% per day upon admission to intensive care

16th January 2023

A systematic review found that skeletal muscle levels reduce by nearly 2% every day during the first week of admission to intensive care

Skeletal muscle loss among critical care patients during the first week of admission to an intensive care unit (ICU) approaches 2 per cent according to the findings of a systematic review and meta-analysis by UK and German researchers.

Critical illness is defined as a state of ill health with vital organ dysfunction and a high risk of imminent death if care is not provided and the potential for reversibility. Moreover, among critically ill patients with sepsis, a considerable number will show signs of severe skeletal muscle wasting and/or ICU-acquired weakness (ICUAW). While the pathophysiology of ICU-AW is incompletely understood, the condition appears to be triggered by critical illness and there is some evidence that skeletal muscle loss is associated with an increased mortality risk. Despite the recognition that skeletal muscle losses occur among critically ill patients, there have been no attempts to summarised the published data on the daily amount of muscle that is lost in ICU patients, which methods are used to monitor muscle size in such patients and on the prevalence of ICU-AW in critically ill patients.

The researchers therefore undertook a systematic review of the topic and searched for studies in which there were at least 20 adult critically ill patients and where the investigators had measured a muscle mass-related variable at two time points during the ICU stay. 

Skeletal muscle loss among ICU patients

The literature search identified 52 relevant studies that included 3251 patients in which 1773 patients had data on on muscle wasting and 1478 on ICU-acquired weakness. Muscle mass was assessed by ultrasound in 85% of studies and the remainder by computed tomography.

During the first week of critical illness, patients were found to have lost an average of -1.75% (95% CI −2.05 −1.45) of their rectus femoris thickness and −2.10% (95% CI −3.17 −1.02) of their rectus femoris cross-sectional area, respectively, every day. In addition, quadriceps muscle thickness decreased by −1.82% (95% CI −2.97 − 0.66) each day and the daily loss in biceps brachii muscle cross-sectional area was −2.23% (95% CI −2.60 − 1.80) and −1.64% (95% CI −3.09, 0.19) for biceps brachii thickness.

Furthermore, the overall prevalence of ICU-acquired weakness was 48% (95% CI 39% – 56%).

The authors concluded that critically ill patients suffer from early and marked muscle wasting, which is about 2% per day but does vary between muscles and depends upon the measurement taken.

Citation
Fazzini B et al. The rate and assessment of muscle wasting during critical illness: a systematic review and meta-analysis. Crit Care 2023

Significant placebo response to pain in cannabinoid clinical trials

5th January 2023

The placebo response appears to play a significant role in pain reduction in clinical trials assessing a patient’s response to cannabinoids

A placebo response makes a significant contribution to the reduction in pain scores seen in cannabinoid clinical trials according to the findings of a systematic review and meta-analysis by Swedish researchers.

Pain is one of the most common symptoms experienced by patients in different health care settings, often leading to loss of function for the affected individual as well as a decline in their quality of life. Although there are wide range of medicines which act as pain-killers, in recent years, there has been increasing interest in the medical properties of cannabinoids. However, the evidence supporting the value of cannabinoids in pain management is limited.

In fact, a 2021 systematic review concluded on how the available evidence neither supports nor refutes claims of efficacy and safety for cannabinoids, cannabis, or cannabis-based medicines in the management of pain. These findings suggest that there may be an important placebo response in such trials and which arise from patients’ positive expectancies.

Furthermore, it is believed that different systems and mechanisms trigger placebo effects that highly impact pain processing, clinical outcomes and create a sense of well-being.

But how large is the placebo response in clinical trials examining the role of cannabinoids in the management of pain? This was the key question addressed in the current study where researchers set out to evaluate the size of placebo responses in double-blind randomised clinical trials in which cannabinoids, cannabis, and cannabis-based medicine were compared with placebo in the treatment of clinical pain. 

The researchers measured the change in pain intensity from before to after treatment, measured as bias-corrected standardised mean difference (Hedges g), which provides an assessment of the effect size. A small effect is represented by a value of 0.2, whereas a medium effect is 0.5 and a large effect 0.8.

Placebo response in cannabinoid trials

The researchers identified a total of 20 eligible trials with 1459 individuals (mean age = 51 years, 56% female). Studies included patients with neuropathic pain and multiple sclerosis.

The effect size of the active drug (cannabinoids) on pain intensity was large (mean Hedges g = 0.95, p  <0 .001). However, pain intensity was associated with a significant reduction in response to placebo, with a moderate to large effect size (mean Hedges g = 0.64, p < 0.001).

In a further analysis, the researchers looked at the media attention paid to these findings and found that this attention was independent of how biased the study was, the extent of the placebo response or how low the treatment effect was.

The authors concluded that placebos contribute significantly to the pain reduction seen in cannabinoid clinical trials. In addition, the positive media attention and wide dissemination possibly leads to high expectations and hence may shape the placebo response in future trials.

Citation
Gedin F et al. Placebo Response and Media Attention in Randomized Clinical Trials Assessing Cannabis-Based Therapies for Pain: A Systematic Review and Meta-analysis. JAMA Netw Open. 2022.

Tafasitamab shows best efficacy in refractory diffuse large B-cell lymphoma

21st December 2022

A systematic review and meta‐analysis found that tafasitamab showed the best efficacy in relapsed/refractory diffuse large B-cell lymphoma

According the findings of a systematic review and meta-analysis undertaken by Korean researchers and presented at the American Society of Haematology conference, 2022, tafasitamab showed a trend for best efficacy among failed autologous stem cell transplantation (ASCT) or ineligible relapsed/refractory diffuse large B-cell lymphoma (DLBCL) patients.

Diffuse large B cell lymphoma is the most common lymphoma, accounting for about 25% to 30% of all the non-Hodgkin lymphomas and which presents as a rapidly growing mass or enlarging lymph nodes in a nodal or extra-nodal site. Non-Hodgkin lymphomas account for about 80% of all lymphomas and while there are more than 30 subtypes, the common ones are diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma. Although 5-year survival rates range from 60% to 70%, up to 50% of patients become refractory to or relapse after treatment. Moreover, outcomes for refractory or relapsed patients are poor, with one study of 861 patients, 636 of whom had refractory disease, finding that the median overall survival was 6.3 months and that only 20% of patients were alive at 2 years. For patients with relapsed/refractory disease, there are several combination chemotherapy regimens available including tafasitamab-cxix, polatuzumab vedotin-piiq, bendamustine as well as CAR T cell therapies. Nevertheless, the most effective treatment remains to be determined.

In the present study, the Korean researchers performed a systematic review and meta‐analysis to identify prospective phase II or III clinical studies evaluating the efficacy of treatments for ASCT-failed or ineligible relapse/refractory DLBCL patients. They used random effects models to estimate one-year progression-free survival rate, complete remission rate, and subgroup differences. In addition, meta-regression models were performed with adjustment for relevant covariates, particularly the median number of previous lines of systemic therapy and CAR T cell therapy was used as a reference treatment in the meta-regression analysis.

Tafasitamab and one-year progression-free survival

The researchers identified 56 cohorts in 50 studies with 3,544 relapsed/refractory DLBCL patients. For the analysis, treatment regimens were divided into nine groups: CAR T cell therapy, chemotherapy, lenalidomide-based therapy, ibrutinib-based therapy, tafasitamab-based therapy, polatuzumab plus bendamustine and rituximab (pola-BR), loncastuximab, selinexor, and others.

The pooled one-year progression-free survival rate was 0.40 (95% CI 0.35 – 0.46) for CAR T cell therapy, 0.23 (95% CI 0.16 – 0.30) for chemotherapy, 0.28 (95% CI 0.19 – 0.37) for lenalidomide and 0.46 (95% CI 0.37 – 0.56) for tafasitamab.

Although CAR T cell treatment was significantly better than many of the others, in fact, loncastuximab, pola-BR, and tafasitamab were all shown to have no significant difference in efficacy to CAR T cell therapy after adjustment for the median number of prior lines of treatment in the meta-regression analysis.

The authors concluded that tafasitamab showed a trend of best efficacy and that CAR T cell therapy was no more effective than tafasitamab, loncastuximab or pola-BR. However, because of the high level of heterogeneity, the authors called for randomised controlled trials to confirm their findings.

Citation
Kim J et al. Comparison of Several Salvage Treatments of Relapsed/Refractory Large B-Cell Lymphoma Including Chimeric Antigen Receptor T-Cell Therapy: A Systematic Review and Meta‐Analysis. Abstract 2986 ASH conference 2022

Higher mean arterial pressure unlikely to prevent AKI in shock and perioperative patients

12th December 2022

A systemic review suggests a higher mean arterial pressure is unlikely to reduce the rate of acute kidney injury (AKI) in patients with shock

A higher mean arterial pressure (MAP) in shock or perioperative patients does not appear to be superior to normotension for the prevention or progression of acute kidney injury (AKI) and the need for renal replacement therapy according to a systematic review by Taiwanese researchers.

Globally, acute kidney injury (AKI) is associated with poor patient outcomes and the available data suggests that the pooled incidence rate of AKI is 21.6% in adults with a 23.9% AKI-related mortality. An acute circulatory failure is the major cause of renal failure in intensive care unit (ICU) patients, since the low cardiac output and/or low mean arterial pressure (MAP) leads to renal hypo-perfusion and AKI. It is necessary therefore to maintain an adequate mean arterial pressure but the level of MAP to adequately protect against worsening of renal function is unknown. However, it is known that hypotensive episodes, i.e., where the MAP is less than 73 mmHg, are associated with progression of AKI in critically ill patients with severe sepsis. Furthermore, other work suggests that mean arterial pressure levels of 70 mmHg or higher do not appear to be associated with improved survival in septic shock. and that elevating above 70 mmHg may increase mortality. 

In the present study the Taiwanese researchers conducted a systematic review and meta-analysis of available randomised clinical trial (RCT) results to try and determine whether a higher MAP might be better than normotension for the prevention and worsening AKI. They searched all of the major databases for studies to comparing higher BP target versus normotension in haemodynamically unstable patients, i.e., those with shock, post-cardiac arrest, or surgery patients. They set the two outcomes of interest as the post-intervention AKI and renal replacement therapy rates.

Mean arterial pressure and AKI

A total of 12 eligible trials with 5759 participants, with shock (57%), non-cardiac (29.3%) and cardiac surgery (13.7%) patients were included in the analysis.

The normotensive target varied depending on the patient cohort. For example, in shock patients the normotensive range was 65 – 70 mmHg, 40 – 60 in cardiac surgery and 60 – 75 in non-cardiac surgery.

When compared against the lower mean arterial blood pressure (i.e., normotension), targeting a higher MAP demonstrated no significant effect on AKI rates in shock (risk ratio, RR = 1.10, 95% CI 0.93 – 1.29), cardiac-surgery (RR = 0.87, 95% CI 0.73 – 1.03) or non-cardiac surgery patients (RR = 1.25, 95% CI 0.98 – 1.60]). Similarly, there was no effect on renal replacement therapy in shock patients from targeting a higher MAP (RR = 1.10, 95% CI 0.93 – 1.03) or for either for cardiac and non-cardiac patients.

Interestingly, among shock patients with premorbid hypertension, targeting MAP above 70 mmHg significantly lowered the risk of renal replacement therapy (RR = 1.20, 955 CI 1.03 – 1.41, p < 0.05).

The authors concluded that targeting a higher MAP in shock or perioperative patients may not be superior to normotension, except in shock patients with premorbid hypertension but called for future studies to assess the effects of a high MAP target to preventing AKI in hypertensive patients across common settings of haemodynamic instability.

Citation
Tran PNT et al. Higher blood pressure versus normotension targets to prevent acute kidney injury: a systematic review and meta-regression of randomized controlled trials. Crit Care 2022

Review finds honey improves cardiometabolic risk factors

2nd December 2022

A systematic review suggests that eating honey may improve both lipid and glycaemic health markers when consumed as part of a healthy diet

Consumption of honey appears to improve cardiometabolic risk factors through favourable changes in glycaemic control and lipid levels according to a systematic review and meta-analysis by Canadian researchers.

Honey is a natural product formed from the nectar of flowers by honeybees and has a long history of use for both nutritional needs and its medicinal properties. Nevertheless, honey contains free sugars, and the World Health Organisation has called for adults and children to reduce their daily intake of free sugars to less than 10% of their total energy intake and have included honey as a source of free sugars. Despite the presence of free sugars, honey also contains flavonoids and phenolic acids which have a positive impact on health, through antioxidant and anti-inflammatory properties. These effects had led to the widespread use for the treatment of eye diseases, bronchial asthma, throat infections, tuberculosis, thirst, hiccups, fatigue, dizziness, hepatitis, and wounds, as well as being taken as a supplement.

Although excessive intake of free sugars is linked to higher rates of obesity, the cardiometabolic effects of honey intake have not been systematically explored and was the subject of the present study by the Canadian researchers. The team searched for both randomised and non-randomised controlled feeding studies that examined the effect of oral honey intake on adiposity, glycaemic control and lipid levels. The researchers measured the mean differences (MD) between participants assigned to honey and control arms.

Honey intake and cardiometabolic risk

A total of 18 controlled feeding trials in 1105 participants with a median age of 41.2 years (54% female) and which considered 33 different comparisons were identified and included in the analysis.

The researchers identified a significant reduction in total cholesterol (MD = -0.18 mmol/L, p = 0.011), LDL cholesterol (MD = -0.30 mmol/L, p = 0.0024) and an increase in HDL cholesterol (MD = 0.07 mmol/L, p < 0.001).

In addition, oral honey reduced fasting glucose (MD = -0.20 mmol/L, p = 0.017). However, there was also an increase of interleukin-6 (IL-6) levels (MD = 0.37 pg/ml, p = 0.046) and tumour necrosis factor alpha (MD = 1.44 pg/ml, p = 0.019). The reasons for an increase in IL-6 levels is unclear but some data points to how release of the cytokine from the contracting skeletal muscle is perhaps one of the molecular signals promoting the beneficial effects of exercise.

There were also differences based on the floral source and by processing, with robinia, clover and raw honey more beneficial than the processed form.

Summarising the benefits, the authors state that a median intake of 40 g of honey for 8 weeks appears to be sufficient to deliver the cardiometabolic benefits. Nevertheless, despite these positive findings, the authors did identify that much of the evidence was of low certainty and called for more studies focusing on the floral source and the processing of honey to increase the certainty of this evidence.

Citation
Ahmed A et al. Effect of honey on cardiometabolic risk factors: a systematic review and meta-analysis. Nutr Rev 2022

Anticoagulation reversal agents equally effective and safe after intracranial haemorrhage

25th November 2022

Anticoagulation reversal agents used for intracranial haemorrhage have similar levels of efficacy and safety according to a systematic review

Anticoagulant reversal agents use following an intracranial haemorrhage, all appear to have a similar level of efficacy and safety according to the findings of a meta-analysis by US researchers.

The direct oral anticoagulants (DOACs) are increasingly preferred over warfarin in DOAC-eligible patients with atrial fibrillation and patients with venous thromboembolism. In fact, the more widespread introduction of these agents has been generally well received by patients who report a high level of treatment satisfaction.

Nevertheless, anticoagulant agents are associated with an increased risk of bleeding and the annual rate of intracranial haemorrhage in those taking DOACs is 0.1% to 0.2%. Several anticoagulant reversal agents are currently available and approved. For example, andexanet alfa (AA) has been approved where reversal of anticoagulation is needed due to life-threatening or uncontrolled bleeding with apixaban or rivaroxaban.

Similarly, idarucizumab is approved for the specific reversal of dabigatran. Prothrombin complex concentrates have been developed to contain highly concentrated coagulation factors and one particular agent, 4-factor prothrombin complex concentrate (4F-PCC), has been found to be a good treatment option in patients requiring DOAC reversal.

However, the newer and traditional agents have not been directly compared. As a result, in the present study, the US researchers undertook a systematic review of the safety and efficacy of these non-specific (i.e., 4F-PCC) and targeted anticoagulant reversal agents in patients with DOAC-related intracranial haemorrhage (ICH).

Included studies were those in which patients with an intracranial haemorrhage had been treated with a DOAC, there was reversal of the DOAC and anticoagulant reversal outcomes such as thromboembolism and mortality were reported. The primary outcome was the successful reversal of anticoagulation.

Anticoagulant reversal of DOAC therapy

A total of 36 studies including 1832 patients with an ICH and a mean age of 76 years (57% male) met the inclusion criteria.

For patients treated with 4F-PCC, anticoagulant reversal occurred in 77% of patients, compared to 75% for AA and 82% for idarucizumab when reversing dabigatran.

In terms of safety, all-cause mortality was also broadly similar for 4F-PCC and AA (26% vs 24%) and lower for idarucizumab (11%). Thromboembolic events were similar for 4F-PCC and idarucizumab (8% vs 5%) and slightly higher for AA (14%).

The authors concluded that while there were no direct head-to-head comparisons available, their findings suggested that the overall anticoagulation reversal, mortality, and thromboembolic event rates appeared similar among available DOAC reversal agents for managing ICH.

Citation
Chaudary R et al. Evaluation of Direct Oral Anticoagulant Reversal Agents in Intracranial Hemorrhage: A Systematic Review and Meta-analysis. JAMA Netw Open 2022.

Review suggests serum vitamin D levels might protect against developing COVID-19

21st November 2022

Serum vitamin D levels may protect against the development of COVID-19 but appears to have little impact on other outcomes such as mortality

Serum vitamin D levels might offer some protection against infection from COVID-19 but there is a lack of positive evidence for other outcomes such as reducing disease severity or mortality, according to the conclusion of a systematic review (available as a preprint) by researchers from the Philadelphia College of Osteopathic Medicine, US.

Much has been made of the potential protective role of higher serum vitamin D levels and COVID-19. This arises from studies showing how vitamin D affects multiple immune system mechanisms including a dampening of the entry and replication of the virus, reducing concentrations of pro-inflammatory cytokines, raising levels of anti-inflammatory cytokines, enhances the production of natural antimicrobial peptide and activation of defensive cells such as macrophages. Much of the hope for the vitamin comes from a 2017 systematic review in which the vitamin was given as a supplement, concluding that it protected against acute respiratory tract infections and how those who had a deficiency of vitamin D or who did not receive bolus doses, experienced the most benefit. Moreover, throughout the COVID-19 pandemic, emerging data has demonstrated an association between deficiency of vitamin D and the severity of infection and subsequent post-infection mortality.

In the present review, the US researchers looked at studies assessing vitamin D levels and how this impacted on the level of infection, levels of inflammatory markers, disease severity and mortality. The team compared the effects of sufficient vitamin D (serum 25(OH) D levels > 30 ng/ml, insufficient (21 – 29 ng/ml) and deficient levels (< 20 ng/ml).

Serum vitamin D levels and COVID-19 outcomes

A total of 19 studies were included. Among those who tested positive for COVID-19, the median vitamin D levels were 27.08 nmol/L and 48.67 nmol/L in those who were negative. The authors termed this difference to be ‘near significant’ (p = 0.059).

In some of the included studies, elevated levels of C-Reactive Protein (which is a marker for inflammation) and therefore disease severity, were found to be significantly associated with low levels of vitamin D. In one such study, inpatients with a median serum vitamin D levels < 12 ng/ml had more severe disease compared to those with median values > 12 ng/ml (p = 0.004). However, this was not a consistent finding.

In relation to length of hospital stay (used as a measure of disease severity), studies were mixed, with some highlighting a significant association and others no difference. In fact, median vitamin D levels were 45.02 nmol/L in those categorised as having moderate severity disease and 38.08 nmol/L in those with severe disease and this difference was not significant (p = 0.22). Finally, the differences in serum levels between those who survived and died of COVID-19 were also not significantly different.

The authors concluded that there seemed to be a correlation between vitamin D deficiency and the likelihood of developing severe illness from COVID-19 when observing studies individually but that when comparing studies on a larger scale, the significant difference seemed to fade.

Citation
Kersh L et al. What is the Impact of Vitamin D Levels on COVID-19 Severity?: A Systematic Review. Research Square 2022

Review finds tixagevimab/cilgavimab effective for immunocompromised patients

17th November 2022

A systematic review of real-world evidence suggests that the combination tixagevimab/cilgavimab is effective for immunocompromised patients

A systematic review by UK researchers, which is currently available as a preprint, has concluded that the monoclonal antibody combination tixagevimab/cilgavimab is effective against COVID-19 breakthrough infections, hospitalisation, intensive care unit (ITU) admission and both all-cause and COVID-19 specific mortality.

Tixagevimab/cilgavimab (Evusheld) is licensed as a pre-exposure prophylaxis of COVID-19 in adults who are not currently infected with COVID-19, without a known recent exposure to an infected individual infected as well as those who are unlikely to mount an adequate immune response to the vaccination against the virus and finally in those where vaccination is not recommended. Both monoclonal antibodies simultaneously bind to distinct, non-overlapping epitopes of the COVID-19 spike-protein receptor-binding domain to potently neutralise the virus. Trial data in those who were at an increased risk of an inadequate response to vaccination showed that COVID-19 occurred in only 0.2% of those given tixagevimab/cilgavimab compared to 1% of patients receiving placebo.  Furthermore, combination treatment has also been found to be effective in protection against progression to severe COVID-19 or death compared to placebo in unvaccinated individuals with mild to moderate disease.

Despite these positive findings, there is limited evidence from a real-world setting and against COVID-19 variants such as Omicron. Moreover, while Evusheld has been approved for use in many countries, the UK government recently took the decision that there is insufficient evidence available to support procurement and deployment of Evusheld through emergency procedures. In an attempt to provide more data on the effectiveness of tixagevimab/cilgavimab in those who are immunocompromised, in the present study the UK researchers sought to assess the efficacy against breakthrough infections, hospitalisation, ITU admission and mortality.

They searched for randomised, controlled trials, observational or cohort studies where the combination was used as prophylaxis and in studies where breakthrough infections were reported. Secondary outcomes reported upon were hospitalisations, ITU admissions and death.

Tixagevimab/cilgavimab outcomes among immunocompromised patients

A total of 17 studies with 24,773 immunocompromised participants of whom, 10,775 had received the combination therapy were included in the analysis.

Overall, the clinical effectiveness of the combination against breakthrough infections compared to control patients was 40.47% (95% CI 29.82 – 49.67, p < 0.0001). The combination was also significantly more effective than control against hospital admissions (69.23%, 95% CI 50.78 – 81.64, p < 0.00001). Moreover, the effectiveness against ITU admission was also very high at 87.89% (95% CI 47.12 – 98.66, p = 0.0008).

In relation to both all-cause and COVID-19-related mortality, tixagevimab/cilgavimab was also very effective with overall values of 81.29% (p < 0.0001) and 86.36% (p = 0.035) respectively.

The authors concluded that their study, based on real-world evidence showed that tixagevimab/cilgavimab proved to be highly effective, particularly during the Omicron wave and called for future trials to evaluate the on-going certain of this benefit.

Citation
Suribhatla R et al. Systematic review of the clinical effectiveness of Tixagevimab/Cilgavimab for prophylaxis of COVID-19 in immunocompromised patients. MedRxiv 2022.