SARS-CoV-2, the virus that causes COVID-19, continues to spread, leading to more than 69,000 deaths worldwide in less than four months. Efforts are progressing to develop a COVID-19 vaccine, but it's still likely 12 to 18 months away.

In the meantime, the pandemic, with over one million confirmed cases worldwide, is driving researchers to find safe and effective therapies for patients with COVID-19, and an antimalarial drug is potentially on the front lines of that effort. While new and repurposed drugs are being tested in clinical trials, some of these promising drugs are simultaneously being used off-label for compassionate use to treat patients.

Related: Coronavirus update: 10 innovations to help combat COVID-19

Some of the medications being used to treat COVID-19 are known to cause drug-induced prolongation of the QTc of some people. The QTc is an indicator of the health of the heart's electrical recharging system. Patients with a dangerously prolonged QTc are at increased risk for potentially life-threatening ventricular rhythm abnormalities that can culminate in sudden cardiac death.

"Correctly identifying which patients are most susceptible to this unwanted, tragic side effect and knowing how to safely use these medications is important in neutralising this threat," says Michael J. Ackerman, M.D., Ph.D., a Mayo Clinic genetic cardiologist. Dr. Ackerman is director of the Mayo Clinic Windland Smith Rice Comprehensive Sudden Cardiac Death Program.

Related: Coronavirus update: Telemedicine and virtual collaboration on the rise as pandemic spreads

A study published in Mayo Clinic Proceedings details more information about potential dangers and the application of QTc monitoring to guide treatment when using drugs that can cause heart rhythm changes. Dr. Ackerman is the senior author of the study.

Hydroxychloroquine is a long-standing preventive and treatment drug for malaria. It is also used to manage and minimise symptoms of inflammatory immune diseases, such as lupus and rheumatoid arthritis. In laboratory tests, hydroxychloroquine can prevent the SARS-CoV and SARS-CoV-2 viruses from attaching to and entering cells. If these antiviral abilities work the same way in animals and humans, the drug could be used to treat patients and limit the number of COVID-19 deaths.

On a cellular level, potential QT-prolonging medications, like hydroxychloroquine, block one of the critical potassium channels that control the heart's electrical recharging system. This interference increases the possibility that the heart's rhythm could degenerate into dangerous erratic heart beats, resulting ultimately in sudden cardiac death.

Accordingly, Mayo Clinic cardiologists and physician-scientists have provided urgent guidance on how to use a 12-lead ECG, telemetry or smartphone-enabled mobile ECG to determine the patient's QTc as a vital sign to identify those patients at increased risk and how to ultimately minimise the chance of drug-induced sudden cardiac death.

"Right now, it is the Wild West out there, ranging from doing no QTc surveillance whatsoever and just accepting this potential tragic side effect as part of 'friendly fire,' to having ECG technicians going into the room of a patient with COVID-19 daily, exposing them to coronavirus and consuming personal protective equipment," says Dr. Ackerman. "Here Mayo Clinic has stepped forward to provide timely and critical guidance."

Dr. Michael J. Ackerman

 

Guidelines for QTc monitoring during treatment

The antimalarial drugs chloroquine and hydroxychloroquine, as well as the HIV drugs lopinavir and ritonavir, all carry a known or possible risk of drug-induced ventricular arrhythmias and sudden cardiac death. Prior to starting treatment with these medications, it is important to get a baseline ECG to be able to measure changes. This starting point measurement could be from a standard 12-lead ECG, telemetry or a smartphone-enabled mobile ECG device.

On March 20, the United States Food and Drug Administration (FDA) granted emergency approval of AliveCor's Kardia 6L mobile ECG device as the only FDA-approved mobile device for QTc monitoring with COVID-19.

The mobile device's ability to remotely provide the patient's heart rhythm and QTc value does not require an extra ECG technician to take the measurement in person, thus saving increased exposure to COVID-19 and the need for more personal protective equipment.

Using the algorithm developed by Dr. Ackerman and colleagues, the potential risk of drug-induced arrhythmias can be rated and used to modify treatment accordingly. For example, patients with a baseline QTc value greater than or equal to 500 milliseconds and those that experience an acute QTc reaction with a QTc greater than or equal to 60 milliseconds from baseline after starting treatment with one or more QTc-prolonging drugs are at greatest risk for drug-induced arrhythmias. Simple QTc countermeasures can be implemented for patients with a cautionary "red light" QTc status if the decision is made to proceed with the intended COVID-19 therapies.

Information guides decisions

There are a number of considerations around the use of off-label drugs to treat COVID-19. The drugs may or may not be available in large enough supply to treat a worldwide pandemic, even at the current compassionate use stage of testing.

It will take careful consideration of COVID-19 patients' circumstances for treating clinicians and patients to decide on the use of drugs or drug combinations that may treat their infection, but which potentially could cause harmful drug-induced side effects.

Dr. Ackerman says that patients under 40 with mild symptoms and a QTc greater than or equal to 500 milliseconds may choose to avoid treatment altogether, as the arrhythmia risk may far outweigh the risk of developing COVID-19-related acute respiratory distress syndrome. However, in COVID-19 patients with a QTc greater than or equal to 500 milliseconds who have progressively worsening respiratory symptoms or are at greater risk of respiratory complications due to advanced age, immunosuppression or having another high-risk condition, the potential benefit of QTc-prolonging medicines may exceed the arrhythmia risk.

"Importantly, the vast majority of patients ― about 90 per cent ― are going to be QTc cleared with a 'green light go' and can proceed, being at extremely low risk for this side effect," says Dr. Ackerman.

Ultimately, the weighing of risks to benefits depends on whether hydroxychloroquine, with or without azithromycin, is truly an effective treatment against COVID-19.

"If it is, we hope that this simple QTc surveillance strategy, enabled by innovation and the FDA's emergency approval, will help prevent or at least significantly minimise drug-induced ventricular arrhythmias and sudden cardiac death, particularly if the treatment is widely adopted and used to treat COVID-19," says Dr. Ackerman.

The healthcare sector is transforming at a substantial pace, and there are several major trends that we are witnessing in the region. However, it is no secret that challenging macroeconomic and geopolitical factors have resulted in liquidity pressures within GCC economies over the past few years. While the healthcare sector has continued to register a healthy yet normalised growth rate, it was not immune.

That being said, healthcare has been active in the region in terms of mergers and acquisitions activity. In my opinion, this will continue, albeit at a different scale, as larger more established, players seek to consolidate and diversify by acquiring smaller operators. It also makes sense for the latter, who in turn wish to monetise and exit.

However, the expected acquisitions will be smaller and would be mainly directed towards niche businesses such as homecare, long term care (LTC), dental and cosmetic surgery, which can be margin accretive and also cash-based. Naturally, this will provide relief from stretching insurance receivables and stress on working capital.

The region’s healthcare sector is also in a strong position to respond to medical crises as they emerge. Take the UAE’s response to the outbreak of the Coronavirus. The UAE Ministry of Health and Prevention is aligned with World Health Organization’s (WHO) scientific recommendations on the preventive measures and precautions that are already implemented across the country’s health facilities to prevent any outbreak of the disease. This is especially true at airports where thermal screening is now mandatory for all passengers. As announced by the UAE Health Minister Abdul Rahman bin Nasser Al Owais, the country was amongst the first to provide state-of-the-art equipment for detecting the Coronavirus.

Impact of technology

As with every aspect of our lives today, the healthcare sector is also benefitting from technology. For instance, mHealth technologies leverage smartphones to make a substantial impact in providing care access to various underserved regions of Africa. Several GCC countries already have a digital transformation framework for healthcare, while the UAE and KSA have already an AI strategy in place for healthcare. In contrast to American and European populations, 67 per cent of patients in the GCC prefer AI-enabled healthcare delivery.

Access to financing

However, the big question is: how do healthcare providers create profitable, sustainable financing structures? The answer is diversification of income and funding sources. For instance, over the past two years, several providers have leaned toward debt capital markets (DCM). While this could be more expensive, it offers longer average life and more back-ended repayment terms to allow greater flexibility for investment.

Other healthcare providers are accessing the equity capital markets (ECM) in the medium term. In my opinion, providers with access to multiple sources of long-term funding via the DCM and ECM will have an edge in sustainable financing.

Outlook

As we head into 2020, there will still be questions around how the sector will tackle key challenges. Nevertheless, most studies indicate that the sector will continue to grow, anywhere between 5 to 8 per cent this year.  Furthermore, given the GCC has an insurance-driven healthcare model, the incentive to control costs will drive payers to put the onus of managing patients’ health better on providers, as well as by controlling reimbursement.

Given the issue of chronic health conditions of GCC citizens, and an ageing population, which suffers from co-morbidities, the focus will be on two fronts for care delivery – prevention before hospitalisation, and post-acute-care in a step-down manner to ensure monitored recovery in cheaper settings, outside of hospitals.

Medical Tourism

Medical tourism is also a key area of focus on the UAE’s agenda. This is reflected in the fact that medical tourism in the country increased 5.5 per cent year-on-year to reach Dh12.1 billion in 2018, with growth supported by government initiatives and the rising number of medical tourists, according to a new analysis by Dubai Chamber of Commerce and Industry. Currently, orthopaedics, sports medicine, dermatology, dentistry and fertility treatment are among the top specialities for medical tourism in Dubai, and the emirate aims to attract 500,000 medical tourists by 2020.

Then, there is specialisation, and centres of excellence. Given the previous supply gaps and anticipated growing demand for healthcare in the UAE and the GCC, there has been substantial investment in healthcare capacities in the region.

While the demand is likely to grow, supply growth has been outpacing it for the past few years, at least in terms of general hospital beds. In the UAE, there were 154 hospitals in the country in 2018, up from 107 in 2013. Based on this, providers, investors and regulators all turn towards specialisation and centres of excellence in areas like cardiology, oncology and diabetes.

However, the key challenge for the GCC is attracting and retaining highly qualified healthcare professionals that would tempt patients to pay a premium here rather than seek treatment elsewhere.

Push towards local pharmaceutical manufacturing

A key element of both the cost control and growth is expected to come from the continuous push towards local pharmaceutical manufacturing. Expectedly, the medical technologies sector is likely to see the highest growth, thanks to increasing demand for new equipment from hospitals, along with digital health, which is witnessing rising adoption from health IT solutions providers and patients for virtual care solutions.

On the pharmaceutical production front, it is expected that the trend of localisation of pharma manufacturing will continue to accelerate. With only 20-30 per cent of products being manufactured domestically, the sector is attractive for local manufacturing.

Saudi Arabia and the UAE have undertaken several local manufacturing initiatives and are likely to continue to invest. Government policies for local manufacturing of branded generics, biosimilars’ for arthritis and cancer drugs are also supportive of this trend.

Overall, if we take all of the above into consideration, it is no exaggeration to state that the healthcare sector in the region, and globally, remains to be amongst the most dynamic sectors. The vital signs are promising and provided the sector continues on its current trajectory, it continues to show a lot of promise.

Karim Amer

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This article appears in the March/April edition of Omnia Health Magazine. Other topics include AI in healthcare, patient safety, mobile healthcare and further updates around on COVID-19 from the healthcare industry.

Read the magazine online today >>

According to the World Health Organization (WHO), one person in six can become seriously ill and can develop breathing difficulties due to Coronavirus. This has made ventilators critical as the devices have been successful in treating pneumonia, which causes inflammation in the lungs.

What does a ventilator do, and how does it help coronavirus sufferers?

According to the American Thoracic Society, a ventilator, also known as a mechanical ventilator, respirator, or a breathing machine, is a life support treatment that helps people breathe when they have difficulty breathing on their own. The machine pumps oxygen into the lungs and the body and helps to get rid of carbon dioxide through the lungs.

Related: Patient Talk Podcast: How double lung transplants are breathing new life into COVID-19 patients

Simply put, a ventilator can help a patient by doing all or some of their breathing, and it’s better than a mask and other devices, as it can deliver higher levels of oxygen. The ventilator also has a humidifier, which adds heat and moisture to the medical air so that it can match the patient's body temperature.

In certain patients with COVID-19, the virus can cause pneumonia and severe inflammation. Therefore, the machine has become an important asset to combat Coronavirus, particularly among elderly and the immuno-compromised population, who could suffer respiratory troubles and multiple organ failure as the virus attacks the lungs.

Related: Should I prone non-ventilated awake patients with COVID-19?

A ventilator is connected to the patient through a tube placed into their mouth or nose and inserted into the windpipe. The process is referred to as intubation. In certain situations, patients may need to undergo surgery to have a hole made in their neck, and a tracheostomy or “trach” tube is inserted through the hole to the trachea. The ventilator then blows gas that consists of air, and oxygen if required into the lungs.

When treating a patient with COVID-19, a ventilator allows the medical team to support their breathing function. Reports have highlighted that even if the lung is failing, a ventilator could provide enough support and buy time for the medical team to help the patient overcome the infection, until the point where their lungs can regain function.

What are the risks of being on a ventilator?

However, a ventilator could cause damage to the lung tissue based on how much pressure is required to help oxygen get processed by the lungs. And patients with COVID-19 often require very high levels of pressure and oxygen as their lungs have increased inflammation.

One of the other risks associated with ventilators is that the tube carrying air and extra oxygen to the lungs might end up being a pathway for dangerous germs. It has been reported that several patients who have been on the ventilator have been exposed to a problem known as ventilator-associated pneumonia.

Some studies have also pointed out that people who are conscious while on the ventilator might experience feelings of panic and sometimes the pain from the tube makes it difficult for patients to relax. Moreover, those who are attached to ventilators for a week or two could suffer long-term physical, mental and emotional issues and may experience post-traumatic stress disorder.

What kind of care does a person need when on a ventilator?

While ventilator machines have been saving many lives of those infected with Coronavirus, it requires a qualified person to operate it. These machines are not only complicated to build and procure, but they are also quite difficult to run and maintain. And while there is much discussion around the dearth of machines, there is less dialogue on the shortage of professionals such as intensive care physicians, anesthesiologists, intensive care nurses, and respiratory therapists to manage ventilators.

The decision to put a patient on the machine is made when it is clear that the lungs have become too inflamed. The level of sedation varies from person to person. A study found that most patients preferred to remain conscious and that having attentive carers helped their perceptions of being on a ventilator.

As the pandemic spreads, will there be enough ventilators?

The rapidly growing shortage of ventilators has become a matter of concern. In the U.S., President Donald Trump has told manufacturers, such as Ford and General Motors, to start making ventilators.

Furthermore, University College London engineers have worked with clinicians and Mercedes Formula One to build the Continuous Positive Airway Pressure (CPAP) device. It is being trialled at several London hospitals and if all goes well, the Mercedes-AMG-HPP group can begin building up to 1,000 of the machines per day. The CPAP device has received approval from the Medicines and Healthcare products Regulatory Agency.

Moreover, a team of scientists and engineers from Oxford University and King's College London has unveiled a low-cost design, which it says could be quickly put into production.

 

The global burden of chronic kidney disease is increasing and is projected to become the fifth most common cause of years of lives lost globally by 2040. According to the National Kidney Foundation, the two main causes of chronic kidney disease are diabetes and high blood pressure, which are responsible for up to two-thirds of the cases.

In the case of kidney failure, also known as end-stage renal disease (ESRD), a kidney transplant is considered the best treatment option because it can increase the chances of living a longer, healthier life.

Alternative to dialysis

In the UAE, the Mediclinic City Hospital’s transplant programme offers patients suffering from end-stage renal disease an alternative to dialysis. The programme enjoys a strong and supportive partnership with Mohammed Bin Rashid University of Medicine and Health Sciences (MBRU) helping to transform the nation's laws on organ donation and transplant and making the service available to the UAE's citizens and residents.

“Our entire community has embraced this endeavour,” says Dr. Farhad Janahi, Assistant Professor of Surgery, MBRU, Consultant Urologist and part of the Mediclinic City Hospital Transplant Team. “We are extremely grateful to all who made this possible.”

This year, Mediclinic City Hospital has also signed a three-party agreement with Al Jalila Children’s Speciality Hospital and MBRU to collaborate on activities related to organ transplant services. The collaboration will ensure that the three entities work closely with the National Transplant Program led by MOHAP as well as other health authorities, government and non-government entities to support transplant efforts in the UAE and the region.

Treatment plan

The transplant committee at Mediclinic City Hospital provides clinical oversight by assessing the suitability of every patient and formally agrees on the most appropriate treatment plan for all cases before proceeding to donation or placing a patient on a waitlist with the National Transplant Committee.

According to Dr. Janahi, the transplant committee is a true multidisciplinary team meeting involving all the involved specialities – surgical, medical, nursing and the medical director – to organise and oversee all renal transplant activities within the hospital.

“Each patient is discussed in the committee meeting and decisions of adding to list or need of further investigation or assessment and, if needed, referral to a specific specialist as needed takes place,” Dr. Janahi explains. “Depending on the patient, some may need immunological, medical or surgical treatment to enhance their overall health prior to kidney transplantation. Also, depending on the blood group and other immunological tests, patients could be on the list for three months and more. Children are given priority.”

While nurses, doctors, paramedics and first responders continue to operate and put their life at risk to help patients, healthcare front-line workers and first responders must protect themselves by implementing a higher level of cleaning and as part of that, disinfection of technology devices is critical to workplace infection control. But there is a right and wrong way to do it.

For medical staff, this can be scanning solutions, printers or mobile computers. It may seem counterproductive to wash your hands multiple times a day if you’re just going to touch a device immediately after, which puts both healthcare workers and patients at risk.

From constant handling by hospital staff, mobile devices become contaminated with bacteria. According to a whitepaper on devices used in healthcare, a typical mobile device has 18 times more bacteria than a public toilet door handle.

Given the rapidly evolving COVID-19 coronavirus situation, how should healthcare workers clean their devices properly to reduce the spread of germs and to mitigate the risk of damaging those devices which is critical in protecting themselves and their patients? Here are some best practices that do just that.

Disinfection versus cleaning

It’s not enough to just clean the glass components or the surfaces of buttons. Hospitals, ambulances, pharmacies and any other health institutions must thoroughly disinfect the plastic parts, such as the housing, as well as the nooks and crannies to prevent the transmission of contagions.

Wiping down a device is not always enough. Even when fingerprints are cleaned from a device, the surface may still be covered with bacteria, so unless the right cleaning agent has been used, it may not necessarily be completely disinfected to use in the current environment.

Implementing immediate processes

The most important thing to consider before implementing a cleaning protocol for devices is that most guidance information on how and what to clean with differs for each device. The first step is to refer to the device user guide to confirm which cleaning agents are safe to use. This includes the purity or formulation levels for each ingredient, including cleaning agents that should never be used.

It is recommended that hospitals and healthcare organisations should implement a device cleaning policy as soon as possible using the original suppliers’ guidelines. This will help ensure that employees are properly disinfecting mobile computers, scanners and printers regularly. In addition, it will reassure third parties that everything has been taken into consideration to help prevent shared technology devices from becoming a potential source of virus transmission.

Wayne Miller

Can an N95 mask protect against the coronavirus?

In these uncertain times, pharmacies, retailers and hospitals are struggling to keep up as demand soars for ventilators, hand sanitisers, test kits – and N95 masks. The more specialised mask, known as an N95 respirator, is said to be the gold standard for pandemic protection and more effective than surgical masks.

Related: Ventilators – the difference between life and death in Coronavirus

A type of personal protection equipment (PPE), the N95 respirator is thicker than a surgical mask and has been designed to achieve a very close facial fit in order to offer efficient filtration of airborne particles. When properly fitted, N95 respirators can filter more airborne particles than face masks.

What does the N95 stand for in N95 masks?

In fact, the designation N95 is a NIOSH (National Institute for Occupational Safety and Health) classification, meaning the mask filters out at least 95 percent of very small airborne particles (0.3 microns), with the N standing for Not resistant to oil.  

Related: Coronavirus update: 10 essential medical devices and supplies for COVID-19 outbreak

N95 masks are regulated in the US by the Centers for Disease Control and Prevention (CDC), NIOSH and Occupational Safety and Health Administration (OSHA).

Why is there an N95 mask shortage?

Mask shortages were experienced across the world as early in the pandemic as February due to enormous domestic demand in China. The WHO also attributed global PPE shortages to misinformation, panic buying and stockpiling. 

Now US hospitals are running out of N95 masks owing to disruption in supply chains. Wholesale N95 mask costs have reportedly quintupled and airfreight charges have tripled. 

The general public are meanwhile advised not to wear a N95 mask. The US Surgeon General asked the public to stop buying masks explaining that it puts healthcare providers and communities at risk if they were unable to acquire them. Similarly in the UAE, the Ministry of Health and Prevention (MoHAP) urged people not to wear a N95 mask unless they are a medical professional treating coronavirus patients.

The supply shortages are leading to healthcare workers reusing their N95 mask, from the US to Germany and Japan, leaving them exposed and in danger.

How long is an N95 mask good for?

According to NIOSH pandemic planning guidance, there isn’t a way of determining the maximum possible number of safe reuses for an N95 respirator as a generic number to be applied in all cases. The CDC also states that in times of shortages, alternatives to N95s should be considered, including other classes of FFRs, elastomeric half-mask and full facepiece air purifying respirators, and powered air purifying respirators (PAPRs) where feasible.

An alternative solution still is the deployment of technology that cleans and reuses N95 masks.

Research, development and lab management company Batelle received FDA Emergency Use Authorization (EUA) to decontaminate up to 80,000 respirator masks per system each day, using concentrated, vapour phase hydrogen peroxide (VPHP). The masks are exposed to the validated concentration level for 2.5 hours to decontaminate biological contaminates, including the coronavirus SARS-CoV-2. 

 

What efforts are being made to get people masks?

N95 shortages have led to the White House ordering 500 million masks following complaints from providers, and corporate America is pitching in to help.

3M has doubled global production to 100 million N95 masks per month, Facebook has contributed 720,000 respiratory masks, Apple has donated 10 million masks and Salesforce delivered 9000 masks.

China’s Alibaba founder Jack Ma has also donated two million masks.

Is there a way of making a DIY N95 mask?

Individuals worldwide are meanwhile manufacturing respirators in response to the global N95 shortage using 3D printing and other techniques.

In the US, for example, a Virginia-based mother’s tweet went viral after her son used a 3D printer to make face mask for his high-risk uncle and others, and a 15 year old is sewing home-made face masks for North Caroline hospitals running out of high-grade N95 respirator masks.

In Italy, Issinova used a 3D printer adapter to convert a snorkeling mask into a non-invasive ventilator for COVID-19 patients. The 3D printed mask was patented it to ensure it was free and CAD drawings were uploaded for all to use.

The FDA however cautions in its guidance on 3D printing of medical devices, accessories, components, that while a 3D printed PPE may provide a physical barrier, it is unlikely to provide the same fluid barrier and air filtration protection as FDA-cleared N95 respirators.

3D Systems, a business co-founded by the inventor of 3D printing, also states that it does not recommend 3D printing of N95 compliant surgical masks and respirators without proper testing.