Day: September 27, 2021

Health Dept Suspends DG Buthelezi over Digital Vibes Tender

Photo by Tingey Injury Law Firm on Unsplash

In the latest development of the R150 million Digital Vibes tender fallout, Health department director-general Dr Sandile Buthelezi has been placed on precautionary suspension 

On Sunday, health ministry spokesperson Foster Mohale  confirmed Buthelezi’s suspension following a Special Investigating Unit (SIU) report into the alleged tender fraud. Deputy DG Dr Nicolas Crisp will take over as acting DG until the completion of Buthelezi’s hearing process. Buthelezi had previously been on leave.

Mohale said that while the R150m Digital Vibes communications contract was already secured when Buthelezi assumed the DG role, it was his inaction in his role as heady of accounting authority regarding the contract that led to the suspension, said Mohale. 

The tender process was rife with irregularities, involving fictitious companies and doctoring scores of bidding companies.

“The procurement process was … a sham, designed and conducted to reach the predetermined result that Digital Vibes would be appointed,” lead investigator Rajendra Chunilall said in the SIU’s founding affidavit.

Former health director-general Precious Matsoso told the SIU that Tahera Mather, a friend of Dr Mkhize’s and a beneficial owner of Digital Vibes, began work at the department straight after Dr Mkhize’s appointment as minister. Matsotso had been pressured by Dr Mkhize to ensure that Mather was hired. Instead of a public tender for the National Health Insurance (NHI) communications contract as advised by the Treasury, it was issued as a closed tender to ten companies.

Two of these companies did not exist and six of which, including a computer equipment supplier and a graphic design company, did not respond as the tender was out of their scope, according to forensic accountant Hesti le Roux’s investigation.

Mather is also alleged to have created a fraudulent profile for Digital Vibes with the relevant skills and experience, including a fake team some of whom never worked for Digital Vibes and were not paid. 

Due to this rigging, only Digital Vibes and Brandswell responded; the latter had the upper hand as its R69m quote was far cheaper than Digital Vibes’ R141m,

However, the department then inexplicably issued a second RFP, amending the requirements.

Brandswell was “irregularly and irrationally” marked down by the department’s five-member tender evaluation committee (TEC), which included deputy director-general Anban Pillay and head of communications Popo Maja. This was despite Brandswell being a “long-standing and reputable communication solution service provider”, Le Roux said.

“Clearly, the recommendation by the TEC to award the contract to Digital Vibes was invalid in terms of the provisions [of] the constitution, because the procurement process was not fair, equitable, transparent, competitive and/or cost-effective. Therefore, the service level agreement that was concluded with Digital Vibes should be declared invalid,” Le Roux concluded.

Source: Times Live

Managing Children Who Swallowed Button Batteries

Photo by Anna Shvets on Pexels

Small, flat ‘button’ batteries are commonly used in many electronic devices, and increasing numbers of children are ingesting button batteries, US data shows. A practice article in the CMAJ’s (Canadian Medical Association Journal) “Five things to Know About…” series highlights some key points for managing button battery ingestion.

  • Injuries from battery ingestion are increasing according to US data. Between 1999 and 2019, the United States National Poison Data System reported a 66.7% increase in yearly ingestion of button batteries and a 10-fold increase in complications.
  • Battery size and type influence complications. Lithium batteries and those 20 mm or larger are more dangerous and can become lodged in the oesophagus, especially in children under six years of age.
  • Urgency of management depends on the location of the battery. Batteries in the oesophagus should be removed immediately by a health care provider to prevent tissue erosion. Urgent removal in a health care setting is advised in children under five years who swallow batteries 20 mm or larger. Otherwise, children should be monitored as outpatients to see if they pass the battery.
  • Honey or sucralfate should be administered after battery ingestion. Honey given to children older than one year by their caregiver (10mL every 10 minutes, up to six doses) before arrival to the hospital and sucralfate administered in hospitals can reduce tissue damage due to swallowed button batteries.
  • Monitor children for long-term complications. Serious complications can occur despite removal of the battery. Caregivers should monitor for symptoms, including gastrointestinal bleeding and vomiting, weeks to months after removal.

Source: Medical Xpress

Consensus Statement Cautions on Paracetamol Use in Pregnancy

Source: Anna Hecker on Unsplash

A consensus statement by 13 doctors in different countries suggests that pregnant people only take paracetamol/acetaminophen if it is medically necessary, Their paper, published in the journal Nature Reviews Endocrinology, the group paracetamol/acetaminophen (APAP). 

In the same journal issue, an accompanying Editorial outlines the consensus statement and noting that its authors are not calling for a ban on the drug being used, instead they are suggesting that it be taken more cautiously by pregnant women because of a possible risk of birth defects.

Research in recent years has shown that it is possible under some circumstances for APAP to alter foetal development which can herald problems with neurological, urological and reproductive disorders in the baby – the authors found evidence of birth defects in 26 out of 29 studies. The authors call for more research into the possible problems with the drug’s use by pregnant women. They also acknowledge – as do several experts in a reaction piece published on the Science Media Centre site – that APAP is the only pain management drug available for pregnant women. And they point out that medical use of APAP is generally warranted when the mother experiences problems that can negatively impact her baby –  such as having a fever. But they also note that pregnant women’s APAP use appears to have crept up into general use as it has gained a reputation as being safe to use as an all-purpose painkiller.

The expert group and the authors of the new paper notably both point out that the recommendation does not differ from that already in use by most OB/GYNs – and similar wording generally appears on bottles of products based on APAP, such as Tylenol.

The consensus statement’s authors say their intention behind the article is to bring renewed and more focused attention to the possibility of APAP use leading to certain birth defects and the conditions under which they might arise. They note that current research has shown, for example, that the risk of harm seems to rise as the duration of APAP use goes up. In light of this, they suggest pregnant women consider using the drug for short term pain management, rather than as a long-term solution.

Source: Medical Xpress

Radiation Therapy Can Reprogram Faulty Heart Cells

Photo from Olivier Collett on Unsplash
Photo from Olivier Collett on Unsplash

New research published in Nature Communications suggests that radiation therapy can reprogram heart muscle cells to what appears to be a younger state, fixing electrical problems that cause life-threatening arrhythmia without the need for an invasive catheter ablation procedure.

In catheter ablation, a catheter is threaded into the heart, and the tissue that triggers ventricular tachycardia is burned, creating scars that block the errant signals. The new study, however, shows that noninvasive radiation therapy can reprogram the heart muscle cells to a younger and perhaps healthier state, fixing the electrical fault in the cells themselves without needing scar tissue to block the overactive circuits. Previous research showed that radiation therapy typically reserved for cancer treatment could be directed at the heart to treat ventricular tachycardia.

Radiation therapy could in theory reproduce the scar tissue of catheter ablation, in a quicker and totally noninvasive procedure, making the treatment available to more severely ill patients. The doctors found that, surprisingly, patients experienced large improvements in their arrhythmias just days to weeks after radiation therapy, much quicker than the months it can take scar tissue to form after radiation therapy, suggesting that a single radiation dose diminishes the arrhythmia without forming scar tissue. Analysis showed the radiation treatment was at least as effective as catheter ablation for certain patients with ventricular tachycardia, albeit for different, unknown reasons.

“Traditionally, catheter ablation creates scar tissue to block the electrical circuits that are causing ventricular tachycardia,” said senior author and cardiologist Stacey L. Rentschler, MD, PhD, an associate professor of medicine, of developmental biology and of biomedical engineering. “To help us understand whether the same thing was happening with radiation therapy, some of the first patients to have this new treatment gave us permission to study their heart tissue – following heart transplantation or if they had passed away for another reason, for example. We saw that scar tissue alone could not explain the remarkable clinical effects, suggesting that radiation improves the arrhythmia in some other way, so we delved into the details of that.”

Radiation treatment triggered heart muscle cells to begin expressing different genes, the researchers found. Increased activity was seen in a signaling pathway called Notch, which is known for its vital role in early development, including in forming the heart’s electrical conduction system.

A single dose of radiation temporarily activates Notch signalling – normally dormant in adult cells – and leading to a long-term increase in sodium ion channels in the heart muscle, a key physiologic change that can reduce arrhythmias.

“Arrhythmias are associated with slow electrical conduction speeds,” Rentschler said. “Radiation therapy seems to kick up the speed faster by activating early developmental pathways that revert the heart tissue back into a healthier state.”

The researchers studied these effects in mice and in donated human hearts. In human samples, the researchers found that these changes in heart muscle cells were only present in areas of the heart that received the targeted radiation dose.

“Radiation does cause a type of injury, but it’s different from catheter ablation,” said co-author and radiation oncologist Julie K. Schwarz, MD, PhD, a professor of radiation oncology and director of the Cancer Biology Division in the Department of Radiation Oncology. “As part of the body’s response to that injury, cells in the injured portion of the heart appear to turn on some of these early developmental programs to repair themselves. It’s important to understand how this works because, with that knowledge, we can improve the way we’re treating these patients and then apply it to other diseases.”

The researchers also found that the beneficial effects of radiation continued for at least two years in surviving patients. And importantly, they were able to demonstrate in mice that a lower dose of the radiation produced the same effect. A lower radiation dose could reduce long-term side effects and allow such treatment in other types of heart arrhythmias. And while Notch was a big player in these effects, Prof Schwarz said it’s not the only pathway involved. The researchers are continuing to investigate how radiation triggers heart cells to revert to a healthier state.

Source: Washington University School of Medicine

Treating a Mutation Tames The ‘Red Devil’ Chemotherapy Drug

Photo by Charles Parker from Pexels

Harmful side effects from the common chemotherapy drug doxorubicin could be caused by a single mutation, according to a study published in Cell Stem Cell.

The cardiotoxic effects of the chemotherapy drug doxorubicin – an infamous drug nicknamed the ‘Red Devil’ because of its bright red colour and side effects – could be prevented in patients with the mutation by treating them with retinoic acid, according to Paul Burridge, PhD, assistant professor of Pharmacology and senior author of the study.

“In the future patients could be given CD1530, or a similar drug, and this would reduce their chances of experiencing cardiotoxicity,” said Prof Burridge.

Doxorubicin is the most common chemotherapy drug and is mostly used in children and in breast cancer. However, patients receiving doxorubicin experience dose-dependent cardiotoxicity; up to 10% of childhood cancer survivors will develop heart failure in the 30 years after their treatment.

A previous study showed that people who experience cardiotoxicity from chemotherapy were more likely to have a genetic variation called a single nucleotide polymorphism (SNP) in a gene called retinoic acid receptor gamma (RARG).

In this study, Dr Burridge and colleagues created patient-derived heart cells with this SNP and administered doxorubicin, finding that those cells indeed were more sensitive to the treatment. After correcting the mutation using genetic editing tools, the additional toxicity disappeared.

“This confirmed to us that RARG is important in doxorubicin cardiotoxicity sensitivity,” Prof Burridge said.

The researchers tried several drugs that could block the downstream effects of this mutation, finding that one drug, CD1530, made cardiomyocytes less sensitive to the chemotherapy. The drug activates retinoic acid receptors that are usually left inactivated in patients with the SNP, preventing activation of a cardio-protective pathway that is ill-suited for chemotherapy.

The investigators hope to test this drug in human patients, thanks to their use of human cells.

“Because all of our data was generated in human cells, there isn’t a need for a second basic research step,” Prof Burridge said. “We believe we will be able to begin the first stages of a clinical trial, testing the safety of RARG agonists and how effective they are in patients.”

Source: Northwestern University

ECG Readings Can Predict Worsening and Mortality in COVID and Influenza

Photo by Towfiqu barbhuiya from Pexels

Specific and dynamic changes on electrocardiograms (ECGs) of hospitalised COVID patients with COVID or influenza can help predict a timeframe for worsening health and death, according to a new Mount Sinai study.

Published in the American Journal of Cardiology, the study shows that shrinking waveforms on these tests can be used to help better identify high-risk patients and provide them more aggressive monitoring and treatment.  

“Our study shows diminished waveforms on ECGs over the course of COVID illness can be an important tool for health care workers caring for these patients, allowing them to catch rapid clinical changes over their hospital stay and intervene more quickly. […] ECGs may be helpful for hospitals to use when caring for these patients before their condition gets dramatically worse,” said senior author Joshua Lampert, MD, Cardiac Electrophysiology fellow at The Mount Sinai Hospital. “This is particularly useful in overwhelmed systems, as there is no wait for blood work to return and this test can be performed by the majority of health care personnel. Additionally, the ECG can be done at the time of other bedside patient care, eliminating the potential exposure of another health care worker to COVID.”

Researchers did a retrospective analysis of ECGs on 140 hospitalised COVID patients across the Mount Sinai Health System in New York City, and compared them with 281 ECGs from patients with laboratory-confirmed influenza A or B admitted to The Mount Sinai Hospital.  
For each patient, the researchers compared three ECG time points: a baseline scan done within a year prior to COVID or influenza hospitalisation, a scan taken at hospital admission, and follow-up ECGs performed during hospitalisation.

They manually measured QRS waveform height on all electrocardiograms – changes in this electrical activity can indicate failing ventricles. The researchers analysed follow-up ECGs after hospital admission and analysed changes in the waveforms according to a set of criteria they designed  called LoQRS amplitude (LoQRS) to identify a reduced signal. LoQRS was defined by QRS amplitude of less than 5mm measured from the arms and legs or less than 10mm when measured on the chest wall as well as a relative reduction in waveform height in either location by at least 50%.

Fifty-two COVID patients in the study did not survive, and 74% of those had LoQRS. Their ECG QRS waveforms reduced approximately 5.3 days into their hospital admission and they died approximately two days after the first abnormal ECG was observed.

Out of the 281 influenza patients studied, LoQRS was identified in 11 percent of them. Seventeen influenza patients died, and 39% had LoQRS present. Influenza patients met LoQRS criteria a median of 55 days into their hospital admission, and the median time to death was six days from when LoQRS was identified. Overall, these results show influenza patients followed a less virulent course of illness when compared to COVID patients.

“When it comes to caring for COVID patients, our findings suggest it may be beneficial not only for health care providers to check an EKG when the patient first arrives at the hospital, but also follow-up ECGs during their hospital stay to assess for LoQRS, particularly if the patient has not made profound clinical progress. If LoQRS is present, the team may want to consider escalating medical therapy or transferring the patient to a highly monitored setting such as an intensive care unit (ICU) in anticipation of declining health,” added Dr Lampert.

Source: The Mount Sinai Hospital / Mount Sinai School of Medicine

Documents Reveal Funding Attempts for Pre-pandemic Coronavirus Research

COVID heat map. Photo by Giacomo Carra on Unsplash

A recent article by The Telegraph revealed documents on grant applications by US and Wuhan scientists to conduct coronavirus research in 2018. However, it is important to note that these grants were not funded, and are not direct evidence of a ‘lab leak’ or research-related origin for the coronavirus. 

The documents, obtained by a scientist-activist group calling itself DRASTIC and confirmed as authentic by a member of the Trump administration, detail grant requests for antigen-bearing nanoparticles and aerosols to be released into bat caves to immunise bat populations. Note that “coronavirus particles” as The Telegraph describes them would be immunising nanoparticles which could describe coronavirus vaccines. Another proposal involved adding “human-specific cleavage sites” to bat coronaviruses to facilitate entry into human cells. The Defense Advanced Research Projects Agency (DARPA) however, refused to fund the work, saying it would have “put local communities at risk.”

What is perhaps more concerning were details of an effort for gain of function research in MERS-CoV, which has a 30% fatality rate, something which an anonymous World Health Organization COVID researcher suggests could have resulted in a pandemic that was “nearly apocalyptic.”

Scientists, however, urge continued impartiality and examining all possibilities, even controversial ones. In an article published on Friday, 24 September in The Lancet, authors point out that there is neither solid evidence for either a natural origin or a for a research origin. In the nineteen months since the beginning of the pandemic, no natural origin has been found despite extensive searching, and independent international researchers do not have access to the investigation sites in China, raw data or samples. However, it took several years for the natural origins of SARS-CoV-1 to be discovered.

They also point out that a research origin for the virus cannot be excluded. Optimisation of the receptor binding domain for human ACE2 could occur through selection or cell cultures, without requiring knowledge of it in advance. Although certain genetic engineering techniques leave signatures in the genome, so-called ‘seamless’ techniques exist. 

“On the basis of the current scientific literature, complemented by our own analyses of coronavirus genomes and proteins, we hold that there is currently no compelling evidence to choose between a natural origin (ie, a virus that has evolved and been transmitted to humans solely via contact with wild or farmed animals) and a research-related origin (which might have occurred at sampling sites, during transportation or within the laboratory, and might have involved natural, selected, or engineered viruses).”

Sources: The Telegraph (paywall)The Lancet