Tag: 25/2/22

Antiepileptics in Comatose Cardiac Arrest Survivors are Ineffective, Study Shows

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A large scale study of comatose intensive care (ICU) patients admitted after cardiac arrest and resuscitation has shown that antiepileptics to treat epilepsy-like brain activity has no effect, and may even prolong ICU stay.

Following a cardiac arrest and resuscitation, patients may need an ICU stay, and are in a coma. By that stage, the cardiac arrest may have damaged the brain to such an extent that half of the patients will not recover from coma. The other half will also have permanent damage, for example of memory functions. It is extremely difficult to predict if a patient will awaken and what their prognosis is, so clinicians make use of EEG (electroencephalography).

In 10–20% of the patients admitted to the ICU after cardiac arrest and resuscitation, there are signs of brain activity that appear similar to epilepsy: unlike an attack this activity is continuous. For a long time, it was unclear if anti-epileptic medication could help better recovery. As a result, some patients received this medication and some did not.

Now, a large-scale study done between 2014 and 2021 on 172 patients has proven that this medication is ineffective: it does not help recovery, even necessitating a longer ICU stay. The researchers, led by Professor Jeannette Hofmeijer of the University of Twente and Rijnstate Hospital in Arnhem, published their findings in the New England Journal of Medicine.

The conclusion from this study is that anti-epileptic medication does not lead to an improved recovery. The findings show that patients may need to stay longer at the ICU: for the patient an undesired situation, and it puts extra pressure on the health care system. 

Aside from patients who show continuous epileptic signals, a small group of patients show signs of a typical epileptic seizure: a short and heavy attack. In these situations, anti-epileptics could help, but this still needs further research.

“Although the outcome of the trial may be disappointing in terms of chances of recovery, it also takes away uncertainties from the family. The signals point at serious brain damage that would lead to a much longer stay at the ICU,” said Prof Hofmeijer.

Source: University of Twente

High CAC and Lipoprotein(a) Scores Greatly Worsen CVD Risk

Healthy red blood cells. Source: NIH

Having both a high lipoprotein(a) and high coronary artery calcium score (CAC) results in a 22% risk of heart attack or stroke over the following 10 years, nearly double the risk of having either condition alone. These are the findings are from a study published in the Journal of the American College of Cardiology (JACC).

Two decades ago, it was recognised that lipoprotein(a) (Lp(a)) concentrations were elevated in patients with cardiovascular disease (CVD). However Lp(a) was not yet proven to be important due to a lack of both Lp(a)-lowering therapy and evidence that reducing Lp(a) levels improves CVD risk. Recent research has added to the evidence 

“We are hopeful that by making the connection between Lp(a) and CAC as dual risk drivers, we can raise awareness in the medical community and improve earlier heart attack prevention for these patients,” said cardiologist Parag Joshi, MD, Associate Professor of Internal Medicine at UT Southwestern. “Our data may also expedite the development of treatments designed specifically for this high-risk population.”

About one sixth of people in the U.S. have high Lp(a), driven largely by genetics. Coronary artery calcium (CAC) is a marker of plaque deposits around the heart. 

Cardiology researchers confirmed the Lp(a) and CAC connection by comparing data from two landmark cardiovascular trials, the Dallas Heart Study, an ongoing comprehensive study of 6000 diverse and heart-healthy patients conducted from 2000 to present, and the Multi-Ethnic Study of Atherosclerosis (MESA) 6000-participant study investigating early-stage atherosclerosis.

The researchers found that participants with combined high Lp(a) and high CAC had a 22% 10-year risk of heart attack or stroke, compared with a 10-15% 10-year risk in patients who had either risk factor alone.

The team identified three distinct risk-related trends:

  • High Lp(a), high CAC: These individuals face the highest 10-year risk of heart attack or stroke.
  • High Lp(a), zero CAC: 10-year heart attack and stroke risk is low when there is no CAC, even if Lp(a) is high.
  • Low Lp(a), high CAC: 10-year heart attack or stroke risk is higher than average but lower than with high LP(a) and high CAC combined.

“Establishing the connection between Lp(a) and CAC means we can move to the important next phase of research, which will be defining and personalizing early screening protocols to identify patients at high risk of heart attack,” said Dr Joshi. “With further research, this could mean selectively scanning patients with high Lp(a) for their CAC score, and studying therapies specifically designed to reduce Lp(a) among patients with high CAC.”

Source: UT Southwestern Medical Center

SA COVID Study: ‘No Longer at Code Red’, Prof Madhi Says

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Commenting on a recently published South African study showing a high COVID antibody sero-prevalence and decoupling of hospitalisation and death rates, first author Professor Shabir Madhi said that “we [are] no longer at “code red’.”

The study, published in the New England Journal of Medicine, was conducted in Gauteng from October 22 to December 9, 2021, showed a high sero-positivity rate even as the Omicron wave started. Under-12s (56%) had the lowest rate of sero-positivity, while it was 80% in over-50s and 85% in inner city residents. Unsurprising, vaccinated individuals had much higher rates (93%) than unvaccinated ones (68%). Epidemiologic data showed that the incidence of COVID infection increased and subsequently declined more rapidly during the fourth wave than it had during the three previous waves.

The researchers imputed 10.4 million infections, compared to the <1 million COVID cases recorded before Omicron. The researchers also evaluated COVID epidemiologic trends in the province, including cases, hospitalisations, recorded deaths, and excess deaths from the start of the pandemic through January 12, 2022.

At time of Omicron wave onset, 59159 Covid attributable deaths using excess mortality data (rate 396/100,000) in Gauteng. Infection fatality risk for Gauteng 0.57% pre-omicron (substantially higher than 0.019% imputed for seasonal flu pre-Covid calculated using similar methods).

In Gauteng at the start of the Omicron wave. vaccine coverage 36% for at least 1 dose in Gauteng, but 61% in over-50s (responsible for >80% deaths pre-Omicron). The sero-survey showed that, 70% of vaccinated were also infected pre-omicron, indiciating a substantial prevalence of hybrid immunity

Prof Madhi further noted analysis of the incidence trends shows a “massive decoupling” of COVID cases to hospitalisation and death rates over the course of Omicron dominance, which was seen in all age groups.
Omicron was responsible for only 3% of COVID deaths compared to 50% for those in Delta-dominant waves. In the 50-59 age group, Omicron was responsible for only 2% of deaths compared to 53% of Delta-dominant deaths.

They also found that children under 12 were not seriously affected during the Omicron wave, with the Omicron wave making up 26% of hospitalisations and 17% of deaths versus 39% and 47%, respectively with the Delta wave.

The researchers concluded that the SA experience indicates that we are now moving into the convalescent phase of the COVID pandemic. Prof Madhi noted in his tweets that this is likely to be similar in other countries that have had a low or modest vaccine uptake, but which have also seen high rates of natural infection – which, in low- and middle-income countries, has likely been accompanied by significant under-reporting of COVID fatalities. 

Given low rates of vaccine rollout and donations, Africa should focus on vaccinating its vulnerable elderly population, Prof Madhi recommended.

He tweeted that SA had expressed optimism that the pandemic had reached a turning point “which many in high income countries dismissed as ’empirical’ and not applicable to their settings despite high vaccine coverage,” subsequently materialised around the world wherever COVID was “not [a] zero-sum game.”

Hypersensitivity Link Between MRI and X-Ray Contrast Agents

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People with a history of hypersensitivity to iodine-based contrast agents for X-ray based scans, are also susceptible to similar reactions from commonly used MRI contrast agents, according to a large, eight-year cohort study. The study, published in the journal Radiology, also found that premedication or switching to a different MRI contrast agent may reduce risk in patients who have had previous contrast agent reactions.

For a long time, gadolinium-based contrast agents (GBCA) have been used to enhance visualisation of organs, tissues and blood vessels on MRI and provide a more accurate depiction of disease. Though GBCA are relatively safe, recent studies have reported several adverse reactions related to their use, including allergic-like hypersensitivity reactions, such as rash and flushing.

These reactions are increasing in incidence with the widespread use of GBCA, prompting an urgent need for research into risk factors, according to the study’s senior author Hye-Ryun Kang, MD, PhD.

Analysing more than 330 000 cases of GBCA exposure in 154 539 patients over an eight-year period, the researchers found 1304 cases of allergic-like hypersensitivity reactions, for a rate of 0.4%. In patients who had a previous GBCE reaction, the average recurrence rate was 15%.

Acute allergic-like hypersensitivity reactions, or those that occur within one hour of contrast administration, accounted for 1178 cases, while a far smaller number of 126 cases were delayed allergic-like hypersensitivity reactions, or those that occur beyond the first hour and mostly within one week after exposure.

The risk of allergic-like hypersensitivity reactions to GBCAs was higher in those with a history of similar reactions to iodinated contrast media. Normally, having a history of iodinated contrast media hypersensitivity was not thought to be a risk factor for hypersensitivity to GBCAs and vice versa, because of their structural and compositional differences.

“The results of our study challenge this idea,” Dr Kang said.

An underlying predisposition to drug allergies in susceptible patients could be the cause, Dr Kang said, as opposed to any cross-reactivity associated with structural similarities between iodinated contrast media and GBCA. In fact, the risk of hypersensitivity reactions to iodinated contrast media was also higher in those who previously experienced a similar reaction to GBCA.

“Thus, physicians should be aware that patients with a history of hypersensitivity to one of iodinated contrast media or GBCA are at greater risk of developing hypersensitivity reactions to the other,” she said.

Analysis of the data showed that premedication, typically with steroids and antihistamines, and changing the GBCA showed preventive effects in patients with a history of acute allergic-like hypersensitivity reactions. Patients who received premedication and before MRI or were switched to a different GBCA showed the lowest rate of recurrence. Only premedication significantly reduced the incidence of reactions in patients with a history of delayed reactions.

“As the most important preventive measure is avoidance of the culprit agent, a precise record of previously used GBCA should be kept for all patients,” Dr. Kang said. “Physicians should discuss appropriate premedication strategies with their patients prior to MRI procedures.”

Dr Kang nevertheless stressed that contrast-enhanced MRI examinations are invaluable in the diagnosis and follow-up of various diseases, and the overall risk remains low.

“As most of these reactions are mild, we believe the benefits of MRI outweigh the potential risks associated with GBCA use,” she said.

Dr Kang recommended that in all patients receiving an MRI with GBCA exposure, a detailed history of previous hypersensitivity allergic reactions be conducted, and when necessary, appropriate prevention measures should be implemented, such as using premedication and switching to different GBCA types.

Future work would be to perform studies with larger populations to identify possible risk factors and effective preventive strategies for delayed hypersensitivity reactions to GBCA.

Source: Radiological Society of North America

Severe COVID Raises Risk of Pregnancy Complications

Source: Pixabay

A University of Oxford study of over 4000 pregnant women indicates that severe COVID in pregnancy increases the risk of pre-labour caesarean birth, a very or extreme preterm birth, stillborn birth, and the need for admission to a neonatal unit.  

The study, published in Acta Obstetricia et Gynecologica Scandinavica, included 4436 pregnant women hospitalised in the UK with symptomatic COVID from March 1, 2020 to October 31, 2021, of whom 13.9% of had severe COVID. As well as having increased risks of adverse pregnancy-related outcomes, women with severe infection were more likely to be aged 30 years or over, be overweight or obese, be of mixed ethnicity, or have gestational diabetes compared with those with mild or moderate infection.  

“This new analysis shows that certain pregnant women admitted to a hospital with COVID face an elevated risk of severe disease. However, it shows once again the strongly protective effect of vaccination against severe disease and adverse outcomes for both mother and baby,” said senior author Marian Knight, FMedSci, of the University of Oxford. “This study emphasises the importance of ensuring that interventions to promote vaccine uptake are particularly focused towards those at highest risk.”

Source: Wiley