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7th September 2022
A systematic review and meta-analysis by a team from Beijing, China, has suggested that as the COVID-19 virus mutates, giving rise to new variants of concern, the overall incubation time (IT) has been steadily reducing and is as little as 3.4 days for the omicron variant.
The time before the symptoms of a viral infection first appear represents the incubation time (IT) and this metric helps with the differential diagnosis, especially when patients present with largely non-specific acute respiratory viral infection symptoms, because different viral infections have longer or shorter ITs. For example, according to the European Centre for Disease Prevention and Control, for disease outbreaks, the mean incubation period of Ebola virus disease has been estimated at 6.3 days but this can be as short as 2 days or as long as 21 days. In contrast, the IT for respiratory syncytial virus is short at about 3 to 5 days. Knowledge of the IT can often provide important information during an disease outbreak, for example, when infected individuals will be symptomatic and most likely to spread the disease. Some data suggests that the average serial interval for COVID-19 – the time from illness onset in a primary case (infector) to illness onset in a secondary case (infectee) – is close to or shorter than its median incubation period. In other words, there is likely to be a substantial proportion of secondary transmission prior to illness onset.
For the present study, the Chinese team wanted to obtain an estimate of the incubation time for COVID-19 and with the emergence of several variants over time, whether the IT was any different. A further consideration was if the incubation time varied in adults compared to older adults or children and if the severity of infection had any impact.
The researchers searched through the major databases and included studies where the IT was one of the primary outcomes and which they set as the outcome of interest for their study. This was defined as the time from when the infection occurred to the onset of signs and symptoms or the first positive test.
Incubation time and COVID-19 variants
A total of 142 articles with 8,112 patients were included in the analysis, roughly two thirds of which (65.5%), where conducted between January 2020 and March 2020.
The estimated mean incubation time for COVID-19 was 6.57 days (95% CI 6.26 – 6.88 days) although in studies, this ranged from 1.80 to 18.87 days. In 119 studies that examined the original or wild strain of the virus, the mean IT was broadly similar (6.65 days).
However, when considering the different variants, it seemed that the mean IT time was reducing. For example, for the Alpha variant, the mean IT was 5 days (95% CI 4.94 – 5.06), 4.5 days for Beta, 4.41 days for Delta but only 3.42 days for the Omicron variant.
In subgroup analysis, the mean IT was 7.43 days in adults 60 years of age but this was not significantly different to the overall estimated mean. However, the mean IT in those under 18 years of age was 8.82 days and this was significantly different to the overall mean estimate (p < 0.001). There was no significant of disease severity on the mean IT.
The authors concluded that the incubation time of the COVID-19 variants appears to have become shorter over time although these differences were not significant but were a key factor in determining the isolation period.
Wu Y et al. Incubation Period of COVID-19 Caused by Unique SARS-CoV-2 Strains: A Systematic Review and Meta-analysis JAMA Netw Open 2022
31st August 2022
Greater regular physical activity reduces the risk of infection, hospitalisation, severe illness and death from COVID-19 in comparison to those who are inactive according to the findings of a systematic review and meta-analysis by a team of Spanish researchers.
Some degree of physical activity is better than none but greater regular physical activity is best for optimal health outcomes according to a World Health Organisation guideline from 2020. Physical activity has a beneficial impact on the immune system and also appears to have protective associations against infectious disease mortality. Moreover, it also appears that the converse is true, particular in relation to COVID-19. For example, in a study of over 48,440 adult patients with a COVID-19, those who were physically inactive had a higher risk of hospitalisation, admission to intensive care and death compared to those who were consistently meeting physical activity guidelines. But the extent to which greater regular physical activity impacts on adverse COVID-19 outcomes has not been quantified and was the purpose of the present systematic review and meta-analysis by the Spanish team.
The researchers looked for studies in adult patients with and without a COVID-19 diagnosis, where the exposure of interest was physical activity and when the outcomes of interest, e.g., infection, hospitalisation, were measured. The outcomes were assessed and pooled using odds ratios and relative risks.
Greater regular physical activity and COVID-19 outcomes
A total of 16 studies with 1,853610 participants and a mean age of 53.2 years (53% women) were included in the analysis. The amount of physical activity was self-reported in most of the studies though in cases where it was measured, this involved direct assessment using accelerometers or smart devices.
Adults engaging in greater regular physical activity and in comparison to those who were classed as inactive, had a lower risk of infection with COVID-19 (relative risk, RR = 0.89, 95% CI 0.84 – 0.95, p = 0.014), hospitalisation (RR = 0.64, 95% CI 0.54 – 0.76, p < 0.001), severe illness (RR = 0.66, 95% CI 0.58 – 0.77)) and death (RR = 0.57, 95% CI 0.46 – 0.71, p = 0.001).
In subgroup analysis, the researchers found that the beneficial effects of greater regular physical activity were independent of both study design and the instrument used. The team also identified a non-linear dose-response relationship between physical activity when expressed as metabolic equivalent of task (MET)-min per week and severe COVID-19 illness and death but not for either infection or hospitalisation. In other words, there was a flattening of the dose response between regular physical activity and death at 500 MET-min per week and which is equivalent to 150 – 300 minutes of moderate intensity physical activity per week.
The authors concluded that their findings highlighted the importance of physical activity in lowering the risk of infection hospitalisation and severe outcomes in COVID-19, particularly where this level of activity matched the guideline-recommended amounts of 500-MET min/week.
Ezzatvar Y et al. Physical activity and risk of infection, severity and mortality of COVID-19: a systematic review and non-linear dose–response meta-analysis of data from 1 853 610 adults Br J Sports Med 2022
23rd August 2022
Increased amounts of all types of leisure activities e.g., cognitive, physical and social reduce the risk of developing all-cause dementia (ACD) including Alzheimer’s disease (AD) and vascular dementia (VD) according to a systematic review and meta-analysis by a team of Chinese researchers.
Dementia is a syndrome characterised by a deterioration in cognitive function beyond that which might be expected from the usual consequences of biological ageing and currently, across the globe, affects some 55 million people. Although there are several types of dementia, the most common is Alzheimer’s disease, followed by vascular dementia. There is currently no cure for dementia and recommendations to reduce risk factors include switching to a healthy diet and staying mentally and socially active. Indeed, there is some evidence that cognitively stimulating leisure activities may delay the onset of dementia in community-dwelling elders although the value of such activities are uncertain. For example, one study found that neither intellectual or physical activity lifestyle factors were associated with AD biomarkers with another concluding that physical inactivity was not associated with all-cause dementia or Alzheimer’s disease.
With some uncertainty over whether any of these leisure activities impact on ACD, for the present study, the Chinese team undertook a systematic review and meta-analysis. They set out to assess the effect of three different forms of leisure activities: physical (PA), cognitive (CA) and social (SA). For the purposes of the study, PA was defined to include walking, playing sports etc, CA, reading books, writing for pleasure or solving crossword puzzles and SA anything that involved communication with others, e.g. attendance at social centres, volunteer work etc. The researchers used regression analysis to determine the relationship between the different leisure activities and ACD and both subtypes, adjusting their results for covariates such as age, gender, education and apolipoprotein E.
Leisure activities and all-cause dementia
The literature review identified a total of 38 eligible studies with 215, 818 participants and a mean age of 45 years at baseline.
Overall, 36 studies were used to investigate the relationship between the different activities and all-cause dementia. The analysis revealed that participation in leisure activities, compared to no participation, was associated with a 17% lower risk of developing ACD (relative risk, RR = 0.83, 95% CI 0.80 – 0.87, p < 0.001). In subgroup analysis, there was also a significant reduction for each of the different forms of activity, e.g., the relative risk for CA was 0.77 (95% CI 0.68 – 0.87).
For AD, there was an 18% lower risk for participation in leisure activities (RR = 0.82, 95% CI 0.74 – 0.90, p < 0.001) and again, while the lower risk was similar for PA and CA, it was non-significant for SA (RR = 0.89, 95% CI 0.63 – 1.26) although the latter activity assessment was based on only a single study.
For vascular dementia, the reduction was even greater at 32% (RR = 0.68, 95% CI 0.54 – 0.86, p = 0.007). However, this association was only significant for PA and not for CA although there were no studies which examined the relationship with SA.
The authors concluded that leisure activities including physical, cognitive and social, were all significantly associated with a reduced risk of incident dementia and that both PA and CA were linked to a lower risk of AD.
Su S et al. Leisure Activities and the Risk of Dementia: A Systematic Review and Meta-Analysis Neurology 2022
17th August 2022
The clinical judgement of the healthcare professionals treating a patient has a better predictive accuracy for whether an individual should be admitted to an intensive care unit (ICU) compared with the use of a risk stratification model, according to a systematic review by a Dutch team based in Amsterdam.
The outcomes for critically ill patients are often time-sensitive and research suggests how emergency department patients whose transfer to intensive care exceeds 6 hours, not only increases the length of stay in hospital but also mortality. Consequently, several early warning scoring (EWS) systems have been developed to help risk stratify patients within an emergency department (ED) to determine outcomes such as mortality or to predict the need for intensive care admission. But does the development of these models mean that clinical judgement is no longer necessary? The available evidence to date suggests that such risk stratification models may be no better than clinical judgement. For example, one study found that a simple clinical assessment by healthcare staff was superior to a formalised triage system to predict short-term mortality among emergency department patients. Similarly, in a study of the Canadian Syncope Risk Score (CSRS) used in an ED for syncope risk stratification, the authors found that the tool had similar predictive accuracy to clinical judgement. Determining whether risk stratification models perform better than simple clinical judgement was the aim the current study by the Dutch team. They focused on several areas: the need for ICU admission, severe adverse events and finally, clinical deterioration and mortality. The team included studies in which the authors had compared either risk-stratification or an EWS with clinical judgement among adult patients in an acute setting, i.e., either at the ED or pre-hospital assessment. The outcomes of interest were the need for ICU admission, severe adverse events, clinical deterioration and death.
Clinical judgement vs adverse patient outcomes
The literature search identified only 6 relevant studies with 6419 participants of which 4 studies were deemed to be at a high risk of bias. Due to the small number of studies, no meta-analysis was undertaken and descriptive analyses were used instead.
For ICU admission, in one sepsis study, the sensitivity of clinical judgement was 91% (95% CI 0.83 – 0.99) and specificity 71% (95% CI 0.60 – 0.82) which was superior to PIRO and MEDS (all p < 0.001). For the second sepsis study which considered mortality, there was no difference between clinicians and the risk-stratification models.
For the prediction of clinical deterioration, only one study was available and there was no difference between the two different forms of assessment. Finally, for the prediction of severe adverse events (ICU admission, cardiac arrest and death), one study reported on the use of MEWS or the clinical judgement of nurses, and while sensitivities were similar (56.6% vs 61.8%, statistical significance was not reported), nurse’s judgement had a higher specificity (94.1% vs 88.5%, nurses vs MEWS).
The authors concluded that while there were only limited data available, it appeared that clinical judgement was superior to risk stratification models for predicting the need for ICU admission and for prediction of severe adverse events. However, both approaches were similar for prediction of clinical deterioration and mortality.
Veldhuis LI et al. Performance of early warning and risk stratification scores versus clinical judgement in the acute setting: a systematic review Emerg J Med 2022
The presence of an emergency department (ED) pharmacist as part of the clinical care team leads to improvements in the quality of medicines use according to the findings of a systematic review and meta-analysis by researchers from the School of Pharmacy and Pharmacology, University of Tasmania, Hobart, Tasmania, Australia.
The term ‘quality use of medicines’ (QUM) encompasses the wise selection of management options and choosing suitable medicines where indicated, together with ensuring that patients and carers have the knowledge and skills to use medicines safely and effectively. However, ensuring QUM within a busy emergency department is challenging with one analysis covering the period 2011 to 2020 finding that the most common prescribed medications mentioned in reports were epinephrine, insulin, hydromorphone, sodium chloride, heparin, Propofol, diltiazem, ketamine, and morphine. Furthermore, serious medication error events occurred most often at the prescribing stage (42.0%) with the most common medication error type being an incorrect dose (42%). Such errors might be reduced by having an ED pharmacist incorporated into the clinical team and there is already some evidence from a 2019 systematic review which concluded that pharmacy-led medication reconciliation significantly decreased the number of medication discrepancies. Nevertheless, the authors of the systematic review also noted how only one study investigated potential adverse drug events in patients receiving ED care and called for further studies to investigate the direct clinical impact of decreased medication discrepancies. Given that the impact and value of an ED pharmacist remains to be fully explored, for the present study, the Australian team undertook a systematic review and meta-analysis, specifically focusing on the effect of adult care, when departments had access to a pharmacist as part of the ED team.
A literature search was designed to uncover studies in which a pharmacist was a part of the ED team and where the impact was compared with usual care. The outcomes considered were changes in the rates or proportions of the medication-related outcomes such as medication errors, the appropriateness of prescribed medicines, length of hospital stay or re-admission.
Emergency department pharmacist and medication-related outcomes
The literature search identified a total of 31 eligible studies and which included 13,242 participants and with individual study sample sizes ranging from 34 to 3,594. The types of included studies were pre-post interventions, cohort studies and randomised, controlled trials.
Not every study could be used for all of the outcomes under examination. However, pooling results from 10 studies showed that an ED pharmacist intervention was associated with an average error rate decrease of 0.33/patient (95% CI -0.42 to -0.23, p < 0.001). Similarly, in a meta-analysis of 10 studies, use of emergency department pharmacists were associated with a 73% lower proportion of patients with at least one error (relative risk, RR = 0.27, 95% CI 0.19 – 0.40, p < 0.001).
Analysis of 7 studies indicated a 58% increased appropriateness of prescribing (RR = 1.58, 95% CI 1.21 – 2.06, p < 0.001) after input from pharmacists. Finally, there was a 30% reduced risk of re-presenting to ED (RR = 0.70, 95% CI 0.52 – 0.94, p = 0.02) and a 38% reduced risk of re-admission (RR = 0.62) after intervention by a pharmacist.
The authors concluded that their data showed how an ED pharmacist improved QUM and called for future studies to examine the cost-effectiveness of ED-based pharmacy interventions.
Atey TM et al. Impact of pharmacist interventions provided in the emergency department on quality use of medicines: a systematic review and meta-analysis Emerg M J 2022
16th August 2022
Tinnitus has been estimated to affect 14% of the world’s adult population or over 740 million people according to the findings of a systematic review and meta-analysis by a group of European researchers.
Tinnitus is defined as the perception of sound in the absence of a corresponding external acoustic stimulus and it best described as a symptom rather than a disease. Identified causes include noise trauma, metabolic diseases such as hypertension and diabetes, together with ear diseases including Meniere’s disease or lesions affecting the eighth cranial nerve. However, a problem for researchers trying to determine the prevalence of tinnitus, is the lack of a standard definition and in a previous meta-analysis of the prevalence, although 40 studies were identified, the authors noted that nearly half of the included studies had a high risk of bias and which therefore limited the generalisability of prevalence estimates.
In the present study, the European team sought to determine the global frequency of tinnitus using an initial umbrella review, which identifies published meta-analyses and a second traditional literature review of original publications. Combining the results, the researchers calculated a pooled estimate of the prevalence in both adults and children, together with an estimate of the prevalence of more severe tinnitus.
Overall tinnitus prevalence
A total of 113 eligible articles were identified although only 83 of these were used to estimate prevalence and 12 for incidence.
The pooled prevalence estimate for tinnitus in adults was 14.4% (95% CI 12.6 – 16.5%) although within the studies, estimates ranged from 4.1% to 37.2%. However, a problem identified in trying to assess prevalence was how studies had asked about tinnitus in different ways, leading to slight differences in prevalence. For example, when asked about ever experiencing tinnitus, the prevalence was 17.5% whereas only only 13.7% when asked if the condition had persisted for more than 5 minutes (13.7%) and slightly lower still, when assessed using a specific scale (9.3%).
Turning to children and adolescents, the estimated prevalence was 13.6% (95% CI 8.5 – 21%) and again there was a wide variation in prevalence (0.7% to 66.9%). There was also an age-related effect, for instance, the prevalence estimate was 13.7% among middle-aged adults and this rose to 23.6% in older adults, though there was little difference between the sexes (14.1% vs 13.1%, male vs female). There were also a significant geographical variation, with 5.2% of those in Africa affected and 21.9% of individuals from South America.
Finally, the researchers estimated that the pooled prevalence of severe tinnitus was 2.3% (95% CI 1.7 – 3.1%) and similar in children and adolescents (2.7%).
When converting the pooled prevalence into estimates of absolute numbers, the authors calculated that there were 749 (95% CI 655 – 858) million adults globally affected by tinnitus and 120 million with severe symptoms.
The authors concluded that their prevalence estimates of tinnitus were of a similar magnitude to the leading causes of years lived with disability such as hearing loss. They called for institutions such as the Global Burden of Disease to play a leading role to boost research on tinnitus and to improve the care of those affected.
Jarach CM et al. Global Prevalence and Incidence of Tinnitus: A Systematic Review and Meta-analysis JAMA Neurol 2022
21st July 2022
The use of intra-articular hyaluronic acid (HA) produces a small, significant increase in knee osteoarthritis pain intensity compared to placebo although this reduction is less than the minimal clinically important difference according of a systematic review and meta-analysis by Swiss and Canadian researchers.
Osteoarthritis is a degenerative condition and which globally affects around 16% of those aged 15 and over but 22⋅9% of individuals aged 40 and over. One form of treatment is viscosupplementation with intra-articular hyaluronic acid and although it provides a clinically meaningful benefit to a large number of patients, emerging evidence indicates that this is largely a result of other factors, including the placebo effect. Nevertheless, a 2021 economic evaluation suggested that intra-articular HA may reduce the use of pain medications, such as non-steroidal anti-inflammatory drugs and opioids and potentially decreasing the overall treatment costs for knee OA over time. Furthermore, a recent US study found that despite the 2013 American Academy of Orthopaedic Surgeons clinical practice guideline recommendation against the clinical utility of hyaluronic acid, services continued to be widely implemented among Medicare beneficiaries. With its widespread use yet apparent lack of evidence, for the present study, the research team decided to perform a systematic review and meta-analysis to examine the evidence on the clinical benefits and safety of the intervention.
The team searched for randomised or quasi-randomised trials in which at least 75% of participants had clinically or radiologically confirmed knee osteoarthritis and where outcomes such as pain, function or adverse events were reported. The primary outcome was set as pain intensity with function and serious adverse events as the two secondary outcomes. Continuous outcomes were analysed as standardised mean differences (SMDs) such that when the SMD was > 0, this was indicative of a better outcome for HA. The researchers also determined that the minimal clinically important difference for HA was -0.37.
Hyaluronic acid and pain intensity
A total of 169 trials with 9,423 participants and a mean age of 62 years (59% women) and with a mean disease duration of 5.2 years were included in the analysis. The median follow-up time for patients after their HA injection was 13 weeks and 12 weeks for functional assessment.
Based on 24 trials (8997 randomised patients), there was a small, but significant though non-clinically relevant reduction in pain intensity after HA injection (SMD = -0.08, 95% CI -0.15 to -0.02, p = 0.02). Based on a 100 mm visual analogue pain scale, this equated to a 2 mm reduction in scores compared to placebo.
For the secondary outcome of function, the pooled estimate was a SMD of -0.11 (95% CI -0.18 to -0.05, p = 0.001) which again was much lower than the minimally important difference. In terms of adverse effects, the use of HA was associated with a significant increased risk of serious adverse events compared to placebo (relative risk = 1.49, 95% CI 1.12 – 1.98, p = 0.003). Overall, 3.7% of patients receiving HA and 2.5% of those given a placebo experienced a serious adverse event.
The authors concluded that HA was associated with a clinically irrelevant reduction in pain intensity and suggested that their findings do not support the broader use of this intervention for knee osteoarthritis.
Pereira TV et al. Viscosupplementation for knee osteoarthritis: systematic review and meta-analysis BMJ 2022
12th July 2022
A network meta-analysis by a collaborate team from the Netherlands, Denmark and the UK has suggested that intermediate dose low molecular weight (LMW) heparins offer the greatest balance of benefit and harm for the prevention of venous thromboembolism (VTE) in acute ill hospitalised patients.
Venous thromboembolism is not uncommon with one US study estimating that a VTE occurs in approximately 100 persons per 100,000 each year and that an estimated one third of these patients will also develop a pulmonary embolism. Furthermore, VTEs are commonly seen in those with limited movement as revealed in another study that observed how 59% of VTWs in the community could be attributed to institutionalisation such as current or recent hospitalisation or nursing home residence. Although any of the available anticoagulants such as intermediate dose LMW heparins, unfractionated heparin or even oral anticoagulants are effective for the prevention of a VTE, there are differences in the risk-benefit profile of each of the different agents leading to differences in guidance produced by national bodies. For example, in the UK, NICE advocates the use of LMW heparins as a first-line treatment for the prevention of venous thromboembolism in acutely ill patients. In contrast, the American Society for Haematology suggests that for acutely ill medical patients, clinicians can use unfractionated heparin, LMW heparins or fondaparinux. These slight differences have no doubt arise because to date, there is a lack of comparative data on the most appropriate anticoagulant type and dose for the management of VTE in acutely ill patients.
For the present study, researchers performed a systematic review and network meta-analysis to assess the benefits and harms of different types and doses of anticoagulant drugs for prevention of venous thromboembolism in acutely ill adults who have been admitted to hospital. To assess the effectiveness of different anticoagulants, they used a composite primary outcome of all-cause mortality, symptomatic venous thromboembolism, major bleeding and serious adverse events.
Intermediate dose LMW heparins and outcomes
A total of 44 randomised trials with 90,095 participants and a median age of 68.5 years (46.5% women) were included in the analysis.
Thirty-six trials reported on all-cause mortality but interestingly, none of the interventions reduced all-cause mortality in comparison to placebo. However, when compared to no intervention, intermediate dose low-molecular-weight heparins led to a significant reduction (odds ratio, OR = 0.79, 95% CI 0.61 to 0.96) as did pentasaccharides (OR = 0.44, 95% CI 0.20 to 0.92).
Intermediate dose LMW heparins were the only intervention to reduce the incidence of symptomatic venous thromboembolism compared to placebo (OR = 0.66, 95% CI 0.46 – 0.93) but all of the interventions were effective compared to no treatment.
Both intermediate dose unfractionated heparin and direct oral anticoagulants were the two groups of agents most likely to increase major bleeding though there were no apparent differences between the different interventions with respect to the incidence of major adverse effects.
Based on these findings, the authors concluded that intermediate dose LMW heparins conferred the best balance of benefits and harms for prevention of venous thromboembolism in acutely ill hospitalised patients. In contrast, unfractionated heparin, in particular the intermediate dose and direct oral anticoagulants had the least favourable profile.
4th July 2022
Electronic noses (e-noses) have been found to have a high level of diagnostic accuracy for the detection of cancer in exhaled breath according to a systematic review and meta-analysis by a group of Dutch researchers.
Volatile organic compounds (VOC) represent the end products of human metabolism and which can be excreted in breath, urine, and faeces. As a result, VOC can be very useful as markers of diseases and given that sampling is both non-invasive and painless, it is ideal for both clinicians and patients. Exhaled breath samples can be analysed using a combination of gas-chromatography and mass spectrometry (GS-MS) and this approach has been used to identify a specific profile of organic compounds that can be indicative of a malignancy. For example, one study has suggested that there is a specific profile of markers for ovarian cancer, whereas another revealed how VOCs exhibited significant differences between nodular goitre patients and normal controls, papillary thyroid carcinoma patients and normal controls. While GC-MS systems are expensive, enoses rely on the binding of the organic volatile components to sensors within the device and which generates a measurable electrical response. However, none of the electronic noses are currently used in clinical practice but could be of value although there has not been a systematic evaluation of the utility of these devices.
Consequently, the Dutch team sought to examine the diagnostic performance of currently available enoses for the diagnosis of cancer in exhaled breath samples and assessed the devices in terms of the sensitivity and specificity derived from an analysis of the receiver operating characteristic curve.
Electronic noses and detection of cancer
A total of 52 publications that included 3,677 patients with cancer were included in the final analysis, all of which were feasibility studies. The number of patients in studies ranged from 10 to 351 and the types of cancer identified included lung, head, neck, gastric, breast, colorectal and prostate. In most studies, patients with cancer were compared with controls, normally healthy volunteers and histopathological analysis was used for diagnostic confirmation.
The pooled sensitivity for all 52 studies was 90% (95% CI 88 – 92%) and the pooled specificity was 87% (95% CI 81 – 92%). However, there was a high degree of heterogeneity for both measures.
The authors noted that many studies did not report on the effect of various endogenous or exogenous factors that could affect the breath profile such as smoking and co-morbidities. They concluded that while electronic noses appeared to be reasonably accurate for the detection of cancer, there was a need for adequately powered studies to establish the value of the technology as part of a patient’s diagnostic work-up.
Scheepers MHMC et al. Diagnostic Performance of Electronic Noses in Cancer Diagnoses Using Exhaled Breath: A Systematic Review and Meta-analysis JAMA Netw Open 2022
29th June 2022
Questions over the added value of combining an intranasal antihistamine to mono-therapy with an inhaled steroid have been raised by a systematic review and meta-analysis by South Korean researchers.
Allergic rhinitis (AR) is characterised by one or more symptoms including sneezing, itching, nasal congestion, and rhinorrhoea. The disorder affects between 10 to 30 percent of children and adults in the United States and other industrialised countries and can can be either seasonal (SAR) or perennial (PAR).
A 2020 AR management guideline recommended that in patients with SAR, the combination of an intranasal corticosteroid (INCS) and an intranasal antihistamine (INAH) or an INCS alone would be an appropriate initial therapeutic choice. Furthermore, the guideline authors suggested that because the combination had a faster onset of action, it was likely to be preferred by patients. In fact, the guidelines do specifically advocate the combination, but only for patients with moderate-to-severe symptoms. A 2019 systemic review supported both the efficacy and superiority of combing the intranasal antihistamine, azelastine and fluticasone for a reduction in patient-reported symptom scores in allergic rhinitis, it did not include any other intranasal antihistamines.
As a result, for the present systematic review the Korean team searched on PubMed, EMBASE and the Cochrane Central Register of Controlled trials, for either randomised or non-randomised trials that included other types of INAH in combination with nasal corticosteroids and considered. In addition, the team also examined trials that included data on the adverse events of both treatments.
Intranasal antihistamines and treatment outcomes
The search identified 13 relevant randomised, controlled trials, 10 of which reported differences in symptom scores and 12 that described adverse events. Two other intranasal antihistamines identified and included in the analysis were bepotastine and olopatadine.
When compared to mono-therapy with an INCS, the combination of an INCS/INAH, reduced the mean morning and evening 12-hour total nasal symptom score (TNSS) more significantly (mean difference, MD = -0.44, 95% CI -0.61 TO -0.27, p < 0.00001) than INCS treatment alone. In addition, the combination also significantly reduced the total ocular symptom score (MD = -0.62, 95% CI -1.05 to -0.19, p = 0.005).
In comparison to INCS mono-therapy, combination treatment also significantly improved the total mean rhinoconjuctivitis quality of life score (MD = -0.24, 95% CI -0.42 to -.06, p = 0.009).
However, despite the enhanced benefit from the combination, it was found to be associated with a significantly greater risk of treatment-emergent adverse effects compared to INCS mono-therapy such as dysgeusia, i.e., a bad/bitter taste in the mouth or throat (relative risk, RR = 1.52, 95% CI 1.28 – 1.81, p < 0.00001).
The authors noted that while the combination of an INCS/INAH was significantly better at alleviating nasal and ocular symptoms, as well as improving quality of life compared to INCS mono-therapy, the improvements did not reach the minimal clinically important difference for either total nasal symptoms or rhinoconjuctivitis quality of life score.
As a result of these findings, the authors concluded that further studies are needed to verify the potential utility of the INCS/INAH combination compared to INCS mono-therapy.
Kim M et al. Intranasal antihistamine and corticosteroid to treat in allergic rhinitis: A systematic review and meta‐analysis Allergy 2022