Adverse effects of tyrosine kinase inhibitors in cancer therapy: pathophysiology, mechanisms and clinical management
Benefits Of Intravenous Thrombolysis In Acute Ischemic Stroke Due To CeAD
Photo Credit: brgfx
The following is a summary of "Intravenous Thrombolysis in Patients With Cervical Artery Dissection: A Secondary Analysis of the STOP-CAD Study," published in the September 2024 issue of Neurology by Shu et al.
Cervical artery dissection (CeAD) is a major cause of ischemic stroke in younger adults, accounting for 25% of cases.
Researchers conducted a retrospective study to assess the benefits and risks of intravenous thrombolysis (IVT) in patients with spontaneous CeAD and acute ischemic stroke symptoms.
They analyzed data from the STOP-CAD study, including 1,653 patients with spontaneous CeAD who presented within 24 hours of acute ischemic stroke symptoms. Patients were divided into 2 groups: those who received IVT and those who did not. Association between IVT and achieving functional independence (modified Rankin Scale scores 0–2) was investigated at 90 days, and symptomatic intracranial hemorrhage (ICH) within 72 hours after CeAD diagnosis.
The results showed 1,653 patients with a median age of 49 years, 35.1% women, and 512 (31.0%) received IVT. The study found that IVT was linked with functional independence at 90 days (aOR = 1.67, 95% CI 1.23–2.28, P=0.001). However, IVT was not associated with an increased risk of symptomatic ICH (aOR = 1.52, 95% CI 0.79–2.92, P=0.215).
They concluded that IVT improved functional outcomes in patients with spontaneous CeAD and suspected ischemic stroke without increasing symptomatic ICH risk, supporting current guideline recommendations for thrombolysis.
Source: neurology.Org/doi/10.1212/WNL.0000000000209843
Overworked… To Death?
"If you work 80 to 100 hours a week, I don't know how you can possibly take care of your health."
So says Jelena Zikic, referring to the widespread issue of overwork in high-pressure industries where employee work extreme long hours – and can suffer the consequences.
"It's a huge problem," says the associate professor at the School of Human Resource Management at York University.
In May, Bank of America employee Leo Lukenas III passed away from acute coronary artery thrombus. According to reports, he had reportedly worked 100 hours per week, and he passed away days after working on a team that completed a $2-billion merger.
While there are no direct links between Lukenas' overworked status and the cause of his death, there have been various reports linking acute stress to thrombosis.
And in August, a 60-year-old employee at Wells Fargo was found dead in her cubicle, four days after she checked into the office at 7 am.
Overwork has long been a hallmark of industries like banking, where the stakes are high, competition is fierce, and long hours are often seen as a rite of passage. However, high-profile incidents such as these are putting a spotlight on the issue, and to better understand the scope of the problem — along with potential solutions — we spoke with three Canadian experts.
Culture of overworkOverwork has become deeply ingrained in certain sectors, particularly banking, consulting, and technology, where long hours are often seen as the norm rather than the exception.
One of the main challenges for HR professionals and frontline managers is managing these excessive work hours, especially when they are embedded in the organizational culture, says Zikic.
"The first issue here to understand is that we're talking about very sector-specific… expectations," she says. "The whole organizational culture, work culture in those specific places is adapted to that type of hours… which are definitely unhealthy and lead to all kinds of health and well-being challenges."
In looking at the broader picture, the sectors with the most extreme forms of overwork often have "achievement-oriented employees," says Matthias Spitzmuller, associate professor at the Smith School of Business at Queen's University, "in part because they are very highly self-motivated, and in part because it's the culture of the organization that they're working for."
In this culture, people work the long hours "out of a sense of self-determination, a desire for fulfillment, a desire for advancement and growth," he says.
"It's a complex interplay — you have got an existing culture that attracts a certain breed of employees who are, in turn, replicating the workplace practices that they see around them."
As a result, it's not just the employer that's at fault, says Spitzmuller.
"But what is true is that the professional service firms, they do have a unique culture, and they also attract a special type of employee."
Role of leadership and performanceLeadership has a huge effect in terms of modeling appropriate behaviour and defining norms, policies, and procedures, he says.
The problem is often worsened by the kinds of behaviours that leaders choose to reward.
"Do you want to celebrate the employee who is close to a breakdown and who is working 80 to 100 hours a week… as a heroic accomplishment?" says Spitzmuller.
"This is an important question regarding performance management as well. So, what is it that you're looking for, and how do you reward or penalize employee behaviours?"
He shared an example from an investment bank, where a senior manager sent an email late on a Friday night, noting who was still at their desks and how that might affect bonuses and promotions.
"The signal that it sends is that you have to be present, you have to work these long hours regardless of the output that you produce — and that's, I think, where the mistake is, if you're only looking at the input factors, as opposed to how much work gets done, and does it get done in a sustainable way?" says Spitzmuller.
Unrealistic work expectationsOne of the fundamental challenges in tackling overwork is the way that the work itself is designed and distributed within organizations.
Unrealistic work expectations often stem from poor task allocation, according to Spitzmuller, referencing research by Adam Grant, a professor at the Wharton School, who advocates for designing jobs so that employees can complete their tasks within the allocated hours.
"If everyone needs to spend 150% of the allocated work hours, then there's just a fatal flaw in terms of how work is designed," he said.
Research has also shown that excessive hours do not translate into higher productivity. In fact, productivity tends to decline when people are sleep-deprived after long hours at work.
"The research is very clear that 15-, 16-, 17-hour work shifts are simply not productive," Spitzmuller says.
In addition, there's the problem of financing or resourcing the solution, says Sunira Chaudhri, litigator and founder of Workly Law in Toronto.
"When you're driving from profits by using human capital to the brink... And expending that resource as far as you absolutely can by not hiring a second person to help… therein lies the problem."
Plus, professionals in Canada are largely exempt from overtime, which contributes to the overwork, she says: "Because employers are protected, that's why we're seeing this happening."
Costly liability to overworkFrom a legal standpoint, overwork can open employers up to significant liabilities, particularly when employees experience burnout or develop health issues due to excessive work hours, according to Chaudhri.
For one, they may then go on disability leave, either short-term or long-term.
"The employer is required to keep that person's job open to them when they return. So, there's ongoing cost in managing that situation, for sure," she says.
And the situation can escalate if the employee decides not to return to the workplace.
"What often happens is that when someone burns out, not only do they avail themselves of those resources, they often don't want to go back to the work environment," Chaudhri says.
In such cases, employees may seek medical advice that the work environment is no longer suitable for their health, leading to further legal action.
"What you see many executives doing… is they assert a constructive dismissal and/or a discrimination claim on the basis of failing to accommodate a disability," she says.
Under Canadian law, specifically the Human Rights Code, employers are required to make inquiries if they observe signs of disability or deteriorating performance due to overwork.
However, many employers avoid making these inquiries because they do not want to acknowledge the underlying issue, says Chaudhri.
"They want, of course, this person to continue working," she says, but this failure to inquire or accommodate can lead to significant legal penalties, including claims for constructive dismissal, human rights violations, and punitive damages "for forcing an individual to work in what most would find to be an intolerable working environment."
Better hiring decisionsGiven the complexity of overwork and the factors driving it, solutions are unlikely to be simple or quick. However, all three experts pointed to potential strategies that could help mitigate the issue.
For one, hiring. Many professional service firms and investment banks specifically target employees who have an inner sense of insecurity that makes them want to work excessive hours, says Spitzmuller, "because that gives them the sense of validation and recognition that they otherwise wouldn't have."
As a result, HR departments should try to a better handle of that, he says.
"It's very important to understand the context in which this is occurring… starting with the type of employees that you're bringing in into an organization."
Then it's about trying to develop a healthy sense of work-life balance, says Spitzmuller, "that does not pit employees against each other or against their best self, consistently trying to repeat the personal best of the number of hours that they've worked in previous weeks."
Regular check-ins with employeesChaudhri suggests that HR departments carry out regular check-ins with employees to assess their capacity and stress levels.
"Capacity is a very nuanced issue, because I think the employer and employee will have very different views of an employee's capacity," she says. "It's not like every employee is made the same way."
Having conversations about capacity during mid-year check-ins or annual reviews could help both employees and employers address overwork before it becomes a critical issue.
"It's a really good way to encourage a conversation around overwork and to address it in a more systematic way, rather than reactively," Chaudhri says.
A lot of the responsibility is on managers to understand the best ways of dividing tasks and how teams work most effectively, says Zikic.
"Part of improving how we feel at work and issues related to overwork is how the jobs are divided and distributed."
Monitoring tools: solution or band-aid?In recent years, some organizations have turned to caps on 80-hour weeks and timekeeping tools as a way to monitor and manage excessive work hours. Bank of America, for instance, has introduced a timekeeping tool to track how long employees are working.
However, Chaudhri cautions about the "unintended consequences" of this approach.
Employees may perceive these tools as instruments of control rather than mechanisms for protecting their well-being, she says.
"What do employees think? They think, 'Well, all my time is being counted for — I better work harder, I better do more.' They don't actually believe that those tools are being put in place to protect them."
Spitzmuller also doesn't think these tools make much sense.
"You're essentially adding an additional tool of control. And I think if you want to move towards healthy workplace practices, you should de-emphasize control mechanisms.
"You should work towards the culture where you trust your employee to take the right decision in terms of how many hours they should be working, and where you have got leadership that also models the appropriate behaviour."
Taking tech to the next level, there are also wearable devices that monitor biometric data, such as heart rate, sleep patterns, activity and social communication, says Zikic.
"Some employers are going to that direction in terms of trying to change the work culture and providing employees with these devices in order to have hardcore data on their wellbeing."
Disconnecting from (over)workOne of the legal frameworks aimed at addressing overwork is the "right to disconnect" law, which has been adopted in parts of Canada.
While new laws may help in setting boundaries, more needs to be done, says Zikic.
"It is really this culture of overwork, in many places, that is an established norm. And so that mentality of what's okay or what's expected of you as an employee is very, very hard to change," she says.
"I think we will only start changing the mindset of leadership and the industry in general, such as banking, especially investment bankers, when we know that the firm will be liable in creating the overworked culture."
It's also possible that the younger generations entering the workforce, particularly those in industries like consulting and banking, will push back against extreme long hours.
"When I talk to our MBA students, they oftentimes say, 'I don't want to work 60 hours, therefore consulting job X or job Y is not suitable for me,'" says Spitzmuller.
There is potentially something different around generations and their expectations of work, says Zikic, noting that younger workers are more likely to prioritize their well-being and seek roles that offer better work-life balance.
"Are they going to say no to certain requirements in work? Are they going to leave jobs when they feel that some other aspects of their life, or things that they like to do outside of work, are not being satisfied?"
Latest storiesWhat Is Pulmonary Embolism? Symptoms, Causes, And Treatment
A pulmonary embolism (PE) happens when a blood clot suddenly blocks an artery that supplies blood to your lungs.
Your blood goes from your heart to your lungs through your pulmonary artery. In the lungs, the blood is supplied with oxygen and then goes back to the heart, which pumps the oxygen-rich blood to the rest of your body.
Pulmonary embolism happens when a blood clot travels through your body to block an artery supplying blood to your lungs. (Photo Credit: SCIEPRO/Science Source.)
When a blood clot gets caught in one of the arteries going from the heart to the lungs, you have a pulmonary embolism. The clot blocks the normal flow of blood.
This blockage can cause serious problems such as damage to your lungs and low oxygen levels in your blood. The lack of oxygen can harm other organs in your body, too. If the artery is clogged by a big clot or many smaller clots, it can cause a deadly pulmonary embolism.
Pulmonary embolisms usually travel to the lungs from a deep vein in the legs. Doctors call this deep vein thrombosis (DVT). These clots form when the blood can't flow freely through the legs because your body is still for a long time, such as during a long flight or drive. It might also happen if you're on bed rest after surgery or illness.
Pulmonary embolisms are divided into three types.
Acute. When you have an acute PE, the symptoms come on suddenly.
Subacute. This type of PE happens slowly over a period — anywhere from 2 to 12 weeks. The symptoms are more subtle, which makes it more difficult to diagnose. Subacute PE carries a higher risk of death than acute PE.
Chronic. In chronic PE, you have symptoms that progressively get worse, including heart failure. This happens when a small blockage remains in your after you've had an acute PE.
Pulmonary embolism can cause a variety of symptoms. Some of the most common ones are:
Other symptoms can include:
It can be difficult to diagnose a pulmonary embolism, and that's especially true if you have another lung or heart problem already. Your doctor will start by asking questions about your medical history to get a clearer picture of what other conditions you might have.
Your doctor will do a physical exam and order tests. They can include:
Blood tests. Doctors will look for a few different clues in your blood. They include:
Chest X-rays. These might be used to rule out other conditions that could cause similar symptoms. But you can have a PE and still have a chest X-ray that looks normal.
Ultrasound. This uses sound waves to look for blood clots in your body. It's also calledduplex ultrasonography, a duplex scan, or compression ultrasonography.
CT pulmonary angiography. This is a type of X-ray that produces 3D images. The test sometimes uses a contrast solution, which you'll get by an IV in your arm or hand. That helps create clearer pictures. This is also called a CT pulmonary embolism study.
Ventilation/perfusion scan. If you need to avoid exposure to radiation from X-rays or the contrast substance used in CT pulmonary angiograms, your health care provider might order this test. It's also called a V/Q scan. You'll have a small amount of a radioactive substance, called a tracer, injected into a vein in your arm. As the tracer moves through your blood, doctors can monitor your blood flow (perfusion) and compare it to your airflow (ventilation).
Pulmonary angiogram. In this test, a thin tube is placed in an artery, usually through your groin. The tube -- called a catheter -- is threaded up into your pulmonary arteries. A special dye is injected into the tube, and X-rays are taken to show where the dye goes. This is one of the best tools to diagnose a pulmonary embolism. However, it carries some risks and requires a high level of skill, so it's not offered everywhere. The test can affect your heart's rhythm, and the dye can cause kidney problems.
MRI. This test uses magnetic fields and radio waves to create pictures of your body's organs. It's not the first choice of test to diagnose a PE, but if you're pregnant, it allows you to avoid radiation that could harm your baby. If you have a kidney condition, it allows you to avoid dyes that might cause problems.
The risk factors are the same as those for DVT. Doctors refer to these as Virchow's triad. They are:
In rare cases, an artery in the lung can be blocked by something other than a clot, such as an air bubble or part of a tumor. If you break a big bone, fat from the bone marrow can sometimes come through the blood and cause blockage.
Other factors that up your risk for PE include:
If you have a PE, your treatment might include medicine, surgery, or other procedures. The goal is to keep the clot from growing and to stop new clots from forming.
Medicine. A couple of different types of drugs may be part of your treatment plan. Blood thinners (anticoagulants) help keep your blood clot from getting bigger and can prevent new ones from forming. Heparin and warfarin are often used to treat PE. You may have anticoagulant drugs injected into a vein or under your skin. You also might receive a different drug that you take by mouth. If your situation is life-threatening, you might get a clot-busting drug through a vein. These drugs are called thrombolytics. They carry certain risks, which is why your health care provider may want to let your clot dissolve on its own.
Surgery. A surgeon might remove the blood clot from your lung using a thin tube inserted through blood vessels. This usually only happens in life-threatening situations.
Vein filter procedure. You might have a filter placed in your body's main vein, which moves blood from your legs to the right side of your heart. The filter catches blood clots before they can reach your lungs. This can be an option if you can't take blood thinners for some reason, or if those drugs aren't working to prevent clots.
Continuing care. You'll need to meet with your doctor regularly and stay on your medication to prevent another clot from forming.
The complications you might experience from a pulmonary embolism include:
A PE that's not diagnosed and treated promptly can be fatal.
Pulmonary embolism during labor or shortly afterward is one of the most serious pregnancy complications you can have. In developed countries, it's the No. 1 cause of death among those who've just given birth.
Among the things that put you at higher risk for PE during or after childbirth are:
The best way to prevent a PE is to try to stop blood clots from forming deep in your veins. This can be challenging if you've been on bed rest after a surgery or illness, or if you just took a long flight.
If you're at risk, here are a few things that may help lower your chances of getting these dangerous blood clots:
Blood thinners . These drugs, also called anticoagulants, keep your blood from forming clots. Your doctor may prescribe them to you while you're in the hospital for surgery. They might also suggest that you keep taking them for some time after you go home.
Your doctor might also recommend blood thinners if you've been hospitalized after a stroke or heart attack, or if you have complications from cancer.
Compression stockings . These are long socks that squeeze your legs. The extra pressure helps blood move through your veins and leg muscles. Your doctor may recommend that you wear them for a while after surgery.
Exercise . Get out of bed and walk when you're getting over a long stay in the hospital or an illness that's kept you in bed for too long. It'll keep the blood in your legs flowing so it doesn't have a chance to pool.
Stretching during trips. If you're on a long flight, try to walk around every few hours. If you can't stand up, flex your ankles by pulling your toes toward you.
Here's another stretch you can try to do while seated:
If you're driving a long distance, stop every hour and stretch your legs.
Also, be sure to drink extra fluids to help you stay hydrated.
Lifestyle changes. Other steps you can take include:
A pulmonary embolism, or PE, is a blockage in the arteries that deliver blood to your lungs. It can happen when a blood clot forms in your leg (deep vein thrombosis) and travels through your body. Symptoms include being out of breath, chest pain, and passing out. Without quick treatment, this can be a life-threatening condition. Doctors may use blood thinners and clot-busting drugs to treat it. In some cases, you might need surgery to remove the clot, or a filter may be placed in your body's largest vein to keep clots from moving up from your legs.
Can you recover fully from a pulmonary embolism?
Once you begin treatment, you should begin to feel better within a week. However, the clot itself can take months or even years to dissolve. How well you recover depends on several factors, including the size of the clot and your overall health.
What is the life expectancy of a person with a pulmonary embolism?
Without prompt treatment, about a third of people with PE die, often within the first few hours at the hospital. Among those who get the right diagnosis and treatment, about 8% die. Your overall health and the cause of your PE play a role in your long-term outlook. One study found that the 1- and 5-year survival rates were around 90%. The exception was among those whose PE was related to cancer; their survival rate was 60% at the 1-year mark and 39% at the 5-year mark.
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