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Take a look at a selection of our recent media coverage:

Type 1 diabetes incidence in children increased during Covid-19 pandemic

3rd July 2023

The incidence of type 1 diabetes in children and adolescents significantly increased during the Covid-19 pandemic compared to pre-pandemic levels, according to a recent meta-analysis.

Suggestions of an association between infection with Covid-19 and a new diagnosis of of type 1 and type 2 diabetes emerged early in the pandemic. However, the causal mechanisms responsible are unclear. Moreover, understanding the nature of any relationship between diabetes and infection with Covid-19 is complicated by several factors including the seasonality of diagnoses and evidence of an estimated 3.4% annual increase in the incidence of the condition.

In trying to untangle the potential association between the rise in cases of type 1 diabetes and infection with Covid-19, a team of Canadian researchers, writing in JAMA Network Open, compared the incidence rates of paediatric diabetes during and before the Covid-19 pandemic.

The team undertook a systematic review and meta-analysis of all medical databases, using subject headings and text terms related to Covid-19, diabetes and diabetic ketoacidosis (DKA). Studies were included in the analysis if these reported differences in incident diabetes cases during compared to before the pandemic, among individuals under 19 years of age.

Researchers set the primary outcome as the change in the incidence rate of paediatric diabetes from before and during the pandemic. The secondary outcome was the change in the incidence rate of DKA among youths with new-onset diabetes during the pandemic.

Type 1 diabetes incidence and Covid-19

In total, 42 studies with 102,984 incident diabetes cases were included in the analysis.

The type 1 diabetes incidence rate was 14% higher during the first year of the pandemic compared with the pre-pandemic period (incidence rate ratio, IRR = 1.14 95% CI 1.08 – 1.21). Nevertheless, this rate increased further during months 13 to 24 of the pandemic compared to the pre-pandemic level (IRR = 1.27, 95% CI 1.18 – 1.37). There was also a higher incidence of DKA compared to before the pandemic (IRR = 1.26, 95% CI 1.17 – 1.36).

The underlying mechanisms responsible for this observed increase are unclear and require further investigation.

Wine drinking associated with reduced risk of adverse cardiovascular outcomes

23rd June 2023

Wine drinking is linked to a lower risk of death from cardiovascular disease but also reduces the risk of developing both cardiovascular and coronary heart disease, according to the findings of a recent meta-analysis.

Previous studies have hinted that the polyphenolic content of wine confers a cardio-protective effect whereas consumption of spirits, increases the risk of ventricular arrhythmias. In fact, evidence points to a J-shaped relationship between wine consumption and vascular risk.

Whether these purported benefits of wine are influenced by potential confounders such as age, gender, smoking status and the duration of follow-up within studies is uncertain. For the present study published in the journal Nutrients, researchers undertook a meta-analysis to examine the association between wine consumption and cardiovascular outcomes and assessed if this association was influenced by personal and study factors. The researchers looked for studies in adults and where the reported outcomes were cardiovascular mortality, cardiovascular disease (CVD) and coronary heart disease (CHD).

Wine consumption and adverse CV outcomes

There were 25 studies with 1,443,245 subjects included in the final analysis.

Wine consumption was associated with a 24% reduced risk of CHD (relative risk, RR = 0.76, 95% CI 0.69 – 0.84). In addition, there were also significant reductions in the risk of CVD (RR = 0.83, 95% CI 0.70 – 0.98) and for cardiovascular mortality (RR = 0.73, 95% CI 0.59 – 0.90).

In a sensitivity analysis, these associations remained statistically significant. However, publication bias was evidence for the link between wine and CVD but not for either CHD or cardiovascular mortality.

In further analysis, the effects of participants’ mean age, the proportion of women in studies, the duration of follow-up or if whether individuals currently smoked, did not impact on the reported associations.

The researchers did caution that increasing wine consumption could be detrimental for patients who are vulnerable to alcohol due to age, medication or pathology. They also suggested that further research is required to differentiate the observed effects by the type of wine.

Review suggests oseltamivir does not reduce risk of hospitalisation for influenza

15th June 2023

Oseltamivir use does not lower the risk of hospitalisation among older and high-risk patients with influzena, according to the findings of a recent systematic review and meta-analysis.

Published in JAMA Internal Medicine, researchers examined whether oseltamivir use in adult and adolescent outpatients with influenza reduced the risk of hospitalisation. They searched for randomised controlled trials that compared oseltamivir against placebo or nonactive controls in outpatients with a confirmed influenza infection. They set the primary outcome of interest as the first hospitalisation but excluded readmissions. In addition, the team also examined a primary safety outcome which was the rate of any adverse event, regardless of grade.

Risk of hospitalisation

A total of 15 eligible trials with 6,295 individuals, of whom 3,443 were assigned to oseltamivir, were included in the final analysis. The participants had a mean age of 45.3 years (53.6% female). Of the 15 studies, 60% were sponsored by Roche, the manufacturer of oseltamivir.

Overall, oseltamivir was not associated with reduced risk of first hospitalisation (Risk Ratio, RR = 0.77, 95% CI 0.47 – 1.27). In addition, the drug failed to reduce hospitalisations among those aged 65 years and older (RR = 0.99, 95% CI 0.19 – 5.13) and in patients considered at greater risk of hospitalisation (RR = 0.90, 95% CI 0.37 – 2.17). 

In terms of the primary safety outcome, patients given oseltamivir experienced significantly more nausea (RR = 1.43, 95% CI 1.13 – 1.82), vomiting (RR = 1.83, 95% CI 1.28 – 2.63) and a composite of gastrointestinal symptoms (RR = 1.21 95% CI 1.02 – 1.45). 

The researchers concluded that oseltamivir use did not reduce the risk of hospitalisation but did lead to an increased risk of adverse gastrointestinal effects. They called for more studies to identify high-risk patients who might benefit from the drug.

Influenza and oseltamivir in context

Oseltamivir is an anti-viral agent used in the management of influenza. However, the benefits of the drug remain unclear. Some evidence demonstrates a clear advantage, whereas another review concluded that the evidence for a clinically significant effects on complications and viral transmission is limited because of a rarity of such events and problems with study design.

During the Covid-19 pandemic, cases of influenza decreased, although it is anticipated that the virus will re-emerge as normalcy returns following the pandemic. Consequently, there is a need to re-evaluate the available treatments for influenza.

Non-invasive tests show similar prognostic value to histology for adverse outcomes in NAFLD

9th June 2023

The use of non-invasive tests provides similar prognostic accuracy compared to histology for adverse outcomes in patients with non-alcoholic fatty liver disease (NAFLD), according to a new study by a UK and European research group.

Published in the The Lancet Gastroenterology and Hepatology, the study used an individual participant data meta-analysis approach to compare the prognostic performance of liver histology for adverse clinical outcomes in adult patients with NAFLD with three non-invasive methods.

The three comparative tests were liver stiffness measurements by vibration-controlled transient elastography (LSM-VCTE), the fibrosis-4 index (FIB-4),and the NAFLD fibrosis score (NFS). The prognostic performance of the index tests was compared using the time-dependent area under the curve (tAUC). The team set the primary outcome as a composite endpoint of all-cause mortality, hepatocellular carcinoma, liver transplantation or cirrhosis complications.

Non-invasive tests performance

A total of 65 eligible studies, made up of 2,518 patients with biopsy-proven NAFLD and a mean age of 54 years (44.7% female), were analysed. Participants were followed for a median of 57 months and the composite endpoint occurred in 5.8% of patients.

At five years, the tAUC was 0.72 (95% CI 0.62 – 0.81) for histology, 0.76 (0.70 – 0.83) for LSM-VCTE, 0.74 (0.64 – 0.82) for FIB-4 and 0.70 (0.63 – 0.80) for NFS. However, pairwise differences were not significant.

Also at five years, there were similar sensitivities and specificities for histologically diagnosed cirrhosis and the three non-invasive markers. For example, histology had a cumulative sensitivity of 33.3% and a specificity of 90.5% and LSM-VCTE a sensitivity of 29.4% and a specificity of 92%.

The authors concluded that given how the non-invasive tests performed as well as histologically assessed fibrosis in predicting clinical outcomes in patients with NAFLD, the tests could be considered as alternatives to liver biopsy in some cases.

NAFLD in context

The global prevalence of NAFLD is estimated at 24%, and it poses a high risk of liver-related morbidity and mortality. This is largely due to, and from, extra-hepatic cancer and cirrhosis.

While it is recognised that more severe fibrosis – that is stages F3 and F4 – is associated with increased risks of liver-related complications and death, fibrosis staging can only be evaluated with a liver biopsy.

Although several non-invasive biomarkers exist and show good diagnostic accuracy, the prognostic value of these non-invasive tests in comparison to liver histology has not previously been assessed.

Low-dose combination of antihypertensives effective as initial therapy

10th May 2023

Use of a low-dose combination of antihypertensive medicines is effective and well-tolerated as a first-line therapeutic approach

A study of nearly 27,000 hypertensive patients identified how roughly a third (32.5%) of patients had uncontrolled disease. Therapy guidelines invariably recommend monotherapy as a first-line approach and combination treatment only if this fails to control blood pressure (BP). Despite this, a meta-analysis of 354 RCTs in 2003, found that a low-dose combination of BP lowering drugs increases efficacy and reduces adverse effects. More recently, another analysis revealed how use of three drugs gave better blood pressure control than increasing dual therapy doses. Whether a low-dose combination (LDC) of three to four drug classes as an initial therapy provides better blood pressure control than monotherapy or usual care is uncertain.

In a recent systematic review and meta-analysis, researchers set out to determine the efficacy and safety of a LDC initial approach to hypertension management. They looked for RCTs that compared LDC to either monotherapy, usual care, or placebo. The primary outcome was the decrease in systolic hypertension using either LDC, monotherapy, usual care or placebo. Other measures assessed were the proportion achieving a BP <140/90 mm Hg, rates of adverse effects and treatment withdrawal.

Low-dose combination and systolic hypertension

A total of 7 trials with 918 patients with a mean age of 59 years (38% female) met the inclusion criteria.

Mean systolic BP was significantly lower with LDC than either monotherapy or usual care (mean difference, MD = 7.4 mmHg). LDC also increased the proportion of participants achieving BP < 140/90 mm Hg at 4 to 12 weeks (Risk Ratio, RR = 1.40, 95% CI 1.27-1.52). These findings were maintained at 6 to 12 months.

Although LDC led to more dizziness (RR = 1.28, 95% CI 1.00-1.63) no other adverse effects or treatment withdrawal occurred.

These findings suggest that LDCs with 3 or 4 antihypertensives is effective and well-tolerated as an initial treatment of hypertension.

Review suggests inhaled isopropyl alcohol useful for nausea and vomiting in ED

4th May 2023

Inhalation of isopropyl alcohol may be a useful treatment for emergency department management of patients with nausea and vomiting

Nausea and vomiting were responsible for 1.6 million US emergency department (ED) visits in 2007. Antiemetic drugs such as ondansetron and metoclopramide are effective. Despite this, there is a lack of evidence to support the efficacy of one drug over any other. There is some evidence that inhaled isopropyl alcohol (IPA) appears effective for post-operative nausea and vomiting (PONV). For example, 70% inhaled IPA is more effective than promethazine in PONV. How well inhaled IPA compares to other anti-emetics is currently unknown.

The present meta-analysis searched for trials using IPA to treat adult ED patients with nausea and vomiting. The primary outcome was set as a change in nausea severity, measured by a validated scale.

Inhaled isopropyl alcohol and nausea reduction

Only two trials with a total of 195 patients met the inclusion criteria. The pooled decrease in nausea severity was 2.18 on a 0-10 scale, favouring inhaled IPA over placebo. A further trial comparing inhaled IPA and oral ondansetron did not meet the inclusion criteria but was useful for a secondary analysis. This analysis found a similar decrease in nausea (2.16).

There were no differences between inhaled IPA and placebo for the number of vomiting episodes.

The authors report that the available evidence suggests that inhaled IPA significantly reduces self-reported nausea in patients presenting to the ED with the condition. However, they note that only 275 participants have evaluated the intervention, adding the need for larger trials of the intervention.

5-alpha reductase inhibitor use not linked to prostate cancer mortality

27th April 2023

A meta-analysis suggests use of 5-alpha reductase inhibitor drugs does not increase the risk of prostate cancer death in men

Prostate cancer (PC) is the second most common cancer in men with over 1.4 million new cases in 2020. Findings from 2003, suggest that 5-alpha reductase inhibitors (5-ARIs) such as finasteride, prevent or delay the appearance of prostate cancer. Other work with another agent, dutasteride, also noted a lower risk of incident prostate cancer. However, in 2011, the FDA warned that 5-ARIs may increase the risk of a more serious form of prostate cancer. Despite this the available data is conflicting. For example, in one study, use of 5-ARIs led to a delay in cancer diagnosis and worsened cancer-specific outcomes in men with PC. In contrast, another could not detect an association between 5-ARI use and prostate cancer death.

In the present study, researchers undertook a meta-analysis on the association of 5-ARI use and death from prostate cancer. The primary outcome was the incidence of PC mortality among 5-alpha reductase inhibitor users and non-users.

5-alpha reductase inhibitor use and prostate cancer

There were 11 studies meeting the inclusion criteria, only one of which was an RCT and the remainder cohort studies. A total of 3,243,575 men were identified, 138,477 of whom were using a 5-ARI drug.

There was no significant association between 5-ARI use and prostate cancer death (hazard ratio, HR = 1.04, 95% CI 0.80 – 1.35, p = 0.79). In addition, there was also no association when restricting the analysis to exclude patients with a PC diagnosis at baseline (HR = 1.0, 95% CI 0.60 – 1.67, p = 0.99). When adjusting for prostate specific antigen level, there was a lower risk of prostate cancer mortality but this was non-significant (HR = 0.76, 95% CI 0.57 – 1.03, p = 0.08).

Analysis identifies extubation failure risk factors in acute brain injury

9th March 2023

A review suggests extubation failure in acute brain injury is more likely in older patients and following longer mechanical ventilation

In a meta-analysis by Canadian and European researchers it was shown that the risk of extubation failure (EF) in acute brain injury is elevated in older patients and following a longer duration of mechanical ventilation.

Patients with acute brain injury admitted to the intensive care unit (ICU) frequently require mechanical ventilation or other forms of respiratory support, as a consequence of respiratory failure due to loss of airway protective reflexes or decreased respiratory drive. In fact, delaying extubation has been shown to increase the incidence of pneumonia and prolong the length of stay in ICU. However, guidelines designed to support the extubation decision-making process have found limited evidence to support clinicians. Identification of prognostic factors of extubation failure are therefore clearly needed but most evidence on such factors has been derived from non-brain injury patient cohorts.

In the current study, researchers undertook a systematic review and meta-analysis in an effort to identify possible prognostic factors that were associated with EF in acute brain-injured adult patients receiving invasive ventilation in an ICU. The team defined extubation failure as unplanned re-intubation within 72 hours of extubation.

Extubation failure prognostic factors

A total of 21 studies with 3,274 patients and a median age of 53 years were included in the analysis and median incidence of EF was 25%.

The researchers found moderate certainty evidence demonstrating that the risk of EF was associated with increased age (adjusted Odds ratio, aOR = 3, 95% CI 1.78 – 5.07, upper vs lower tertile) as well as a longer duration of mechanical ventilation (aOR = 3.47, 95% CI 1.68 – 7.19, upper vs lower tertile).

In contrast, there was moderate certainty evidence that risk of EF was reduced in the presence of intact cough on the day of extubation (aOR = 0.40, 95% CI 0.28 – 0.57) as well as intact swallow (aOR = 0.34, 95% CI 0.21 – 0.54). However, the certainty of evidence for association with any other factors was either low or very low.

The authors concluded that among adult patients with acute brain injury receiving mechanical ventilation for at least 24 hours, there was moderate certainty evidence to suggest that both older age, a longer duration mechanical ventilation and a lack of intact cough or swallow, were associated with increased risk of extubation failure.

Citation
Taran S et al. Prognostic Factors Associated With Extubation Failure in Acutely Brain-Injured Patients: A Systematic Review and Meta-Analysis. Crit Care Med 2023

Aspirin use benefits reduced by statins in those without atherosclerotic disease

1st March 2023

The benefits of aspirin use in myocardial infarction are offset by statin use in patients without atherosclerotic cardiovascular disease

Aspirin use for the prevention of myocardial infarction (MI) appears to be reduced by concomitant statin use in patients without atherosclerotic cardiovascular disease (ASCVD) without affecting the risk of a major bleed according to a meta-analysis by US researchers.

In 2019, US guidance suggested that aspirin should be used infrequently in the routine primary prevention of ASCVD because of lack of net benefit. More recently, the US Preventative Services Task Force has endorsed these earlier recommendations for primary prevention in adults aged between 40 and 59 with a 10% or higher, 10-year risk of CVD. While historically, aspirin was considered to reduce the risk of an MI, in the context of use with other strategies such as statins, one analysis concluded that the effect of aspirin on myocardial infarction risk was significantly attenuated, whereas its major bleeding and haemorrhagic stroke complications were retained.

For the current meta-analysis, researchers wanted to examine the impact on aspirin use with and without statins, specifically in those without ASCVD but at different levels of risk. The team included a range of risk levels from very low (< 5%) through to very high (> 30%). They included trials where patients were prescribed aspirin and followed for at least 12 months and the team determined the absolute risks for cardiovascular outcomes, major bleeding and mortality over 5 years.

Aspirin use with and without statins

In a total of 16 trials with 171,215 patients with a median age of 64 years (46% women), the use of aspirin alone was associated with a 15% lower risk of a myocardial infarction (risk ratio, RR = 0.85, 95% CI 0.77 – 0.95) although the drug did not reduce mortality. However, the drug lead to a higher risk of major bleeding (RR = 1.48, 95% CI 1.32 – 1.66, p < 0.001).

When considering the absolute benefits, the researched calculated that aspirin monotherapy in patients with a very low ASCVD risk, was likely to lead to 3 fewer myocardial infarctions (MIs) per 10,000 patients but 21 more major bleeds. In contrast, when taken in conjunction with a statin, there would be only 1 less MI but 20 more major bleeds. At the other extreme of ASCVD risk (i.e., > 30%), monotherapy might lead to 49 fewer MIs (but 98 major bleeds) but in combination with a statin, there would be 37 fewer MI’s but 94 major bleeds.

The authors concluded that among adults who did not have ASCVD, statin use with aspirin, appeared to attenuate to some extent aspirin’s clinical benefit but without influencing the bleeding risk, suggesting that the risk of a major bleed from taking aspirin exceeded its benefits across all levels of ASCVD risk.

Citation
Khan SU et al. Aspirin With or Without Statin in Individuals Without Atherosclerotic Cardiovascular Disease Across Risk Categories. JACC Adv 2023

Prior COVID-19 infection provides similar protection as two doses of mRNA vaccine

28th February 2023

A systemic review suggests that the protection afforded by a prior COVID-19 infection is at least as high as that from two doses of a vaccine

Researchers from Washington university in the US, performed a systematic review and meta-analysis finding that the protection afforded by a prior COVID-19 infection was high against re-infection from most pre-omicron variants and remained high against severe disease for all variants and was comparable to the protection from a two-dose vaccination with mRNA vaccines.

To date, several studies have suggested that a previous infection with COVID-19 offers some degree of protection against re-infection. However, studies have included different time periods as well as COVID-19 variants yet there are no analyses that have provided an overview of how the level of protection against re-infection varies over time and in relation to the different variants.

In the current analysis, the US researchers extracted data from studies through to September 2022 that examined the reduction in risk of developing COVID-19 in those with a prior COVID-19 infection compared to those without a previous infection. The data were then analysed to show the effectiveness of a prior infection against several outcomes including the risk of re-infection, symptomatic disease and severe disease based on the variant and time since infection.

Prior COVID-19 infection and re-infection outcomes

A total of 65 studies were included in the analysis from 19 different countries.

The pooled protection against re-infection varied depending on the variant ranging from 82% against delta to 90% against alpha. In contrast, the pooled protection against re-infection with omicron BA.1 was 45.3%. The protection against symptomatic disease was broadly similar, e.g. 85% for delta and 87.2% against alpha and only 44% against omicron BA.1.

The protection against severe infection (i.e., hospitalisation or death) was high for delta (97.2%), slightly lower against alpha (79.6%) but actually also high against omicron BA.1 (81.9%).

The pooled protection against ancestral, alpha and delta variants was initially high at 85.2% after 4 weeks but reduced to 78.6% at 40 weeks. In contrast, protection against re-infection from omicron BA.1 rapidly declined to 36.1% at 40 weeks.

The authors concluded that protection against re-infection was high against most variants pre omicron BA.1 adding that this level of protection was at least equivalent, if not greater than that provided by two-dose mRNA vaccines, which has also been observed in a previous study.

Citation
COVID-19 Forecasting team. Past SARS-CoV-2 infection protection against re-infection: a systematic review and meta-analysis. Lancet 2023

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