Tag: 30/8/21

Categories : Cardiovascular Disease Expert OpinionTags :

‘Every Guideline We Write Is Out of Date’ Quips ESC as New Data Emerges

On By ModernMedia
Image by Marcelo Leal on Unsplash

Just as the European Society of Cardiology (ESC) unveiled their new guidelines for the treatment of heart failure, along came some data that the guideline’s authors hint will cause the work to be revised.

The guidelines, which appear in the European Heart Journal, state that so far, there is no treatment shown to reduce mortality and morbidity in patients with heart failure with preserved ejection fraction, however there are positive results from the EMPEROR-Preserved study showing that treatment with empagliflozin robustly reduced hospitalisation risk.

“Every guideline we write is out of date a few days after it’s published. I’m, of course, exaggerating a little bit, but guidelines are dynamic documents. They represent what we know at the time that they’re written and then new information comes out and they have to be updated, and that takes time,” Milton Packer, MD, of Baylor University Medical Center in Dallas, told MedPage Today.

“It’s a process, and we all understand that process; there is no real concept of finality here. We do the best we can with the data we have. And so these guidelines coming won’t represent the results of the EMPEROR-Preserved trial, but the next one will,” Dr Packer added.

Carlos Aguiar, MD, of Hospital Santa Cruz in Lisbon, agreed: “We also know that these new indications do need to go through the regulatory authorities, so it does take some time for the whole process to be concluded.”

“We do need to wait for those approvals also from the regulatory agencies in their reviews for physicians to be able to implement this in clinical practice,” he told MedPage Today.

However, the writers of the 2021 guideline did tweak the comprehensive algorithm for the treatment of heart failure, the highlights of which include:

  • Right heart catheterisation should be considered in patients in whom heart failure is thought to be due to constrictive pericarditis, restrictive cardiomyopathy, congenital heart disease, and high-output states. It may be considered in selected patients with heart failure with preserved left ventricular ejection fraction (LVEF) to confirm the diagnosis.
  • In patients with chronic heart failure with reduced LVEF, dapagliflozin (Farxiga) or empagliflozin are recommended to reduce hospitalisation and mortality risk. As a Class I recommendation, it is based on evidence gleaned from randomised clinical trials.
  • Vericiguat (Verquvo) may be considered in patients with New York Heart Association (NYHA) class II to IV heart failure after worsening with treatment with an angiotensin inhibitor, a beta-blocker, and a mineralocorticoid receptor antagonist, to reduce the risks of cardiovascular mortality or heart failure hospitalisation.
  • For treatment of heart failure with midrange LVEF — a change in term from “mildly reduced” ejection fraction — to reduce hospitalisation and mortality risk, the guidelines suggest a number of treatments including angiotensin inhibitors, beta-blockers, mineralocorticoid receptor antagonists, and the combination agent sacubitril/valsartan but none have strong clinical trial evidence (Class IIb)  .
  • For patients with heart failure with preserved ejection fraction, the current guidelines recommend (Class I evidence) screening for and treatment of aetiologies, as well as cardiovascular and non-cardiovascular comorbidities.
  • After hospitalisation for heart failure, the guidelines recommend (Class I evidence) that patients be carefully evaluated to exclude persistent signs of congestion before discharge and to optimise oral treatment, and that evidence-based oral medical treatment be administered before discharge. An early follow-up visit is recommended at 1 to 2 weeks after discharge to assess signs of congestion and drug tolerance, and to start and/or uptitrate evidence-based therapy.
  • The SGLT2 inhibitors canagliflozin (Invokana), dapagliflozin, empagliflozin, ertugliflozin (Steglatro), and sotagliflozin are recommended in patients with heart failure and type 2 diabetes at risk of cardiovascular events to reduce hospitalisations for heart failure, major cardiovascular events, end-stage renal dysfunction, and cardiovascular death. The SGLT2 inhibitors dapagliflozin, empagliflozin, and sotagliflozin are recommended in patients with type 2 diabetes and heart failure with reduced ejection fraction (Class I evidence). The DPP-4 inhibitor saxagliptin (Onglyza) is not recommended in patients with heart failure (Class III evidence).

Source: MedPage Today

Categories : CancerTags :

Vulnerability Found in Solid Tumours

On By ModernMedia
Source: NCI

Researchers have found a weakness in a key enzyme key for solid tumour cancer cells’ ability to adapt and survive when oxygen levels are low.

The findings, published in Science Advances, will help researchers develop new treatment strategies to limit the progression of solid cancer tumours, which represent the majority of tumour types that arise in the body.

As tumours advance, the blood vessels that they previously relied on become unable to provide oxygen and nutrients to all parts of the tumour, which results in areas of hypoxia. Over time, this hypoxic environment leads to a buildup of acid inside the tumour cells.

To overcome this stress, the tumour cells adapt by releasing enzymes that neutralise the acidic conditions of their environment, enabling the cells to not only survive, but develop into a more aggressive form of tumour capable of spreading to other organs. One of these enzymes is called Carbonic Anhydrase IX (CAIX).

“Cancer cells depend on the CAIX enzyme to survive, which ultimately makes it their ‘Achilles heel.’ By inhibiting its activity, we can effectively stop the cells from growing,” explained senior author Dr Shoukat Dedhar, professor in UBC faculty of medicine’s department of biochemistry and molecular biology and distinguished scientist at BC Cancer.

Previously, Dr Dedhar and colleagues had identified a unique compound, known as SLC-0111 (which is currently being evaluated in Phase 1 clinical trials) as a powerful CAIX enzyme inhibitor. Though the effectiveness of this compound in suppressing tumour growth and spread has been tested in pre-clinical models, other cellular properties diminish its effectiveness.

In this study, the researchers set out to investiagete these cellular properties and identify other weaknesses of the CAIX enzyme with the help of a powerful tool known as a genome-wide synthetic lethal screen. This tool systematically deletes one gene at a time from a cancer cell’s genome to determine if a cancer cell can be killed by eliminating the CAIX enzyme together with another specific gene.

According to Dr Dedhar, they had surprising results and point to an unexpected role of proteins and processes that control a form of cell death called ferroptosis, a form of cell death that occurs from an iron build up which weakens the tumour’s metabolism and cell membranes.

“We now know that the CAIX enzyme blocks cancer cells from dying as a result of ferroptosis,” said Dr Dedhar. “Combining inhibitors of CAIX, including SLC-0111, with compounds known to bring about ferroptosis results in catastrophic cell death and debilitates tumour growth.”

The development of drugs to induce ferroptosis is underway around the world, and this study is contributing to their work.

Source: University of British Columbia

Categories : Environmental EffectsTags :

Obesity Connection to Commonly-used Pesticide

On By ModernMedia
Photo by Arjun MJ on Unsplash

A commonly-used pesticide could be contributing to the global obesity epidemic, according to a new study.

Researchers discovered that chlorpyrifos slows down the burning of calories in the brown adipose tissue of mice. Reducing this burning of calories, a process known as diet-induced thermogenesis, causes the body to store these extra calories, promoting obesity. Chlorpyrifos is banned for use on foods in Canada, and also now banned in the US and, as of last year, the EU, but widely sprayed on fruits and vegetables in many other parts of the world. In South Africa it is banned for residential use but is still used in agriculture.

Scientists made the discovery after studying 34 commonly used pesticides and herbicides in brown fat cells and testing the effects of chlorpyrifos in mice fed high calorie diets. Their findings were published in Nature Communications and could have important implications for public health.

“Brown fat is the metabolic furnace in our body, burning calories, unlike normal fat that is used to store them. This generates heat and prevents calories from being deposited on our bodies as normal white fat. We know brown fat is activated during cold and when we eat,” said senior author Gregory Steinberg, professor of medicine and co-director of the Centre for Metabolism, Obesity, and Diabetes Research at McMaster.

“Lifestyle changes around diet and exercise rarely lead to sustained weight loss. We think part of the problem may be this intrinsic dialling back of the metabolic furnace by chlorpyrifos.”

Steinberg said chlorpyrifos would only need to inhibit energy use in brown fat by 40 calories every day to trigger obesity in adults, which would translate to an extra 2kg of weight gain per year.

He said that while several environmental toxins including chlorpyrifos have been associated with increasing obesity rates in both humans and animals, these studies have mostly attributed weight gain to increases in food intake and not calorie burning.

“Although the findings have yet to be confirmed in humans, an important consideration, is that whenever possible consume fruits and vegetables from local Canadian sources and if consuming imported produce, make sure it is thoroughly washed,” said Steinberg.

Source: Medical Xpress

Categories : Ageing Cardiovascular DiseaseTags :

Screening for AF in the Elderly Using Thumb ECGs Reduces Stroke Risk

On By ModernMedia

Screening for atrial fibrillation in 75- and 76-year-olds using thumb ECGS could reduce the risk of stroke, severe bleeding and death, according to a large-scale Swedish study.

Atrial fibrillation (AF) is associated with a five-fold increased risk of stroke, and the symptoms are often deleterious since large blood clots can form in the heart, breaking free and posing a stroke risk. Still, countries do not screen the general population for atrial fibrillation, but rather treat those patients who are discovered during routine care. This study by the Karolinska Institutet in Sweden and published in The Lancet, investigated the effectiveness of screening for AF.

“There has never really been a study that examines if it would be beneficial to screen for atrial fibrillation, which is why we wanted to investigate it,” said Emma Svennberg, cardiologist at the Karolinska University Hospital, Huddinge, and researcher at the Department of Medicine, Huddinge, Karolinska Institutet.

The study included almost 28 000 participants aged 75 or 76, randomised to be invited either to screening or to a control group, who received standard care. Of those invited to screening, more than half choose to participate. They completed a health questionnaire and performed a so-called thumb ECG (electrocardiogram), which involves placing one’s thumbs on an ECG device that measures the heart’s electrical activity.

Those without atrial fibrillation were asked to record their heart rhythm twice daily for two weeks using the ECG device which they took home. If the device registered irregular heart rhythms, the participants were referred to a cardiologist for a standardised work-up and, if there were no contra-indications, initiation of oral anticoagulant therapy.

The study’s 28 000 participants were then followed for at least five years. More detections of atrial fibrillation were recorded in the screening group, which also had a slightly lower incidence of death, stroke and severe bleeding than the control group.

“In total, 31.9 percent of those in the screening group experienced a negative event compared to 33 percent in the control group,” said Johan Engdahl, adjunct lecturer at the Department of Clinical Sciences, Danderyds Hospital, at Karolinska Institutet. “Now, that may sound like a small difference, but you must bear in mind that only about half of those invited to screening participated and it’s possible we would have seen a more pronounced difference had more people turned up for screening. Those who participated in the screening had significantly fewer negative events.”

Based on the findings, the researchers estimated that at least 2300 cases of stroke or death could be avoided per year in Sweden if a national screening of atrial fibrillation in the elderly was introduced.

Source: Karolinska Institute

Categories : COVIDTags :

Delta Variant More than Doubles Hospitalisation Risk

On By ModernMedia
Source: Mat Napo on Unsplash

In a study of more than 40 000 COVID cases, those infected with the delta variant have about twice the hospitalisation risk as those infected with the alpha variant. The findings were published in The Lancet Infectious Diseases.

The risk of hospitalisation or emergency hospital care within 14 days of infection with the delta variant was 1.45 times greater than the alpha variant. This is the first study reporting hospitalisation risk for the delta versus alpha variants based on cases confirmed by whole-genome sequencing.

Dr Gavin Dabrera, one of the study’s lead authors and a Consultant Epidemiologist at the National Infection Service, Public Health England, said: “This study confirms previous findings that people infected with Delta are significantly more likely to require hospitalisation than those with Alpha, although most cases included in the analysis were unvaccinated.”

The delta variant emerged in India in December 2020 and early studies found it to be up to 50% more transmissible than the alpha variant, which first appeared in the UK. A preliminary study from Scotland previously reported a doubling of hospitalisation risk with the delta variant over the alpha variant and it is suspected that delta is associated with more severe disease. The previous study used patients’ initial PCR test results and determined which variant they had by testing for a specific gene that is more common in the delta variant.

The researchers analysed healthcare data from 43 338 COVID-positive cases in England between 29 March and 23 May 2021. During the study period, there were 34 656 cases of the alpha variant (80%) and 8682 cases of the delta variant (20%). While the proportion of delta cases in the study period overall was 20%, it eventually encompassed two thirds of new COVID cases in the week starting 17 May 2021 (65%), effectively becoming the dominant strain in England.

Around one in 50 patients were admitted to hospital within 14 days of their first positive COVID test (2.2% alpha cases; 2.3% delta cases. After accounting for factors that are known to affect susceptibility to severe illness from COVID, including age, ethnicity, and vaccination status, the researchers found the risk of being admitted to hospital was more than doubled with the delta variant compared with the alpha variant (2.26-fold increase in risk).

It has been shown in multiple studies that full vaccination prevents both symptomatic infection and hospitalisation, for both alpha and delta variants. Indeed, in this study, only 1.8% of COVID cases (with either variant) had received both doses of the vaccine; 74% of cases were unvaccinated, and 24% were partially vaccinated. With the small number of vaccinated people being hospitalised, it is not possible to statistically compare hospitalisation risk between alpha and delta in such cases, so the results of the study apply to unvaccinated or partially vaccinated cases.

One of the study’s lead authors, Dr Anne Presanis, Senior Statistician at the MRC Biostatistics Unit, University of Cambridge, said: “Our analysis highlights that in the absence of vaccination, any Delta outbreaks will impose a greater burden on healthcare than an Alpha epidemic. Getting fully vaccinated is crucial for reducing an individual’s risk of symptomatic infection with Delta in the first place, and, importantly, of reducing a Delta patient’s risk of severe illness and hospital admission.”

Limitations to the study included some demographic groups possibly being more likely to seek hospital care, which could have biased the results, and there may have been changes in hospital admission policy during the period of the study, although adjustment for demographics and calendar time should have minimised such bias. The authors also did not have access to information about patients’ pre-existing health conditions, which are known to affect the risk of severe illness from COVID. By using age, gender, ethnicity, and estimated level of socioeconomic deprivation, they were able to account for this.

Source: Medical Xpress

Categories : COVIDTags :

A KZN Doctor’s Observations and Treatments of COVID

On By ModernMedia
SARS-CoV-2 viruses (yellow) infecting a human cell. Credit: NIH

Dr Shankara Chetty, a general practitioner with a natural science background in genetics, advanced biology, microbiology and biochemistry, has been critically reviewing information that has arisen from observations of the COVID pandemic from around the world. Knowledge gained from a broad natural science background convinced him that there was a missing element in these reports. This is a summary of an article published in Issue 5 of Modern Medicine in 2020.

“A wealth of knowledge of hospital presentations, pathology and investigations has been generated, but there has been a distinct lack of information regarding initial presentation, progression and pathogenesis,” said Dr Chetty.

Type 1 hypersensitivity reaction
When COVID arrived in South Africa, Dr Chetty isolated himself so as to limit interactions with family and the public and erected a tented field clinic in his practice parking so as to be able to examine and follow up on every COVID patient without risk to his other patients. According to him he had a theoretical understanding of the possible pathogenesis but needed to verify his suspicions.

“From the examination, treatment and follow up of over 200 symptomatic COVID patients, it is my opinion that COVID illness has two aetiologies. It is initially a respiratory viral infection with typical symptoms, progression and outcomes over the initial 7 days. On around day 7, a Type 1 hypersensitivity reaction is triggered in those that are sensitive, leading to the sequelae typically seen on admission.

“This reaction causes the release of chemical mediators in the ling, resulting in inflammation, oedema, and in time, massive cell damage. The resultant cellular disruption is what triggers the ‘cytokine storm’ in an attempt to repair damaged cells and remove debris. This release of cytokine produces the variety of pathologies that are seen,” said Dr Chetty.

Rapid response to treatment
His treatment protocol included the use of hydrochloroquine, azithromycin and doxyclcline to combat the viral component and antihistamines, leukotriene receptor antagonists and steroids, amongst others, for the Type 1 hypersensitivity reaction. This protocol produced consistent outcomes, no sequelae, and rapid recovery of all patients. In all, they had no deaths, no hospitalisations and recover of all patients, regardless of age, within 14 days.

“Outcomes of identifying and treating a Type 1 hypersensitivity reaction were most telling in the more severe dyspnoiec patients, with saturations below 85% on presentation that had improvement to over 95% in 24 hours, with outpatient management on room air, negating the need for oxygen or hospitalisation,” said Dr Chetty.

According to Dr Chetty, the rapid response to these medications used to treat Type 1 hypersensitivity reactions confirmed its existence. This could have some serious implications for the future management of the COVID pandemic. Monitoring for a hypersensitivity reaction and prompt treatment would decrease morbidity and mortality significantly.

Source: Modern Medicine