A major global health crisis that we find ourselves facing today is sepsis – the body’s extreme response to infection resulting in organ damage and, in too many instances, death. In the U.S. alone, at least 1.7 million adults develop sepsis each year, almost 270,000 of whom die as a result. Sepsis also constitutes the biggest annual hospital expense, totaling around $24 billion in the U.S. per year.
Sepsis is becoming more prevalent for multiple reasons, including an aging population, more patients living with chronic disease and the evolution of drug-resistant pathogens. According to the World Health Organization, sepsis accounts for almost 20 percent of deaths worldwide – more than prostate cancer, breast cancer and HIV combined – and yet this deadly condition receives far less attention than other severe diseases. With a mortality rate of almost 50 percent, sepsis deserves to be treated with grave concern.
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Avishay Bransky Avishay Bransky, Ph.D., CEO and co-founder of PixCell, is an expert in microfluidics, with extensive industrial experience in applied physics, software and systems engineering. He is one of the inventors of the Viscoelastic Focusing technique, cell analysis methods and the microfluidic based cartridge. Dr. Bransky holds a B.A. in Physics, B.Sc. in Materials […]
While the immune system is designed to protect the body from illness, it can at times miscalculate the severity of an infection and, in response, go into overdrive. Sepsis develops when cytokines — chemicals released by the immune system into the bloodstream to fight an infection – cause inflammation throughout the entire body instead of targeting the affected area. Sepsis mortality comes not as a result of the infection itself, but from the body’s sudden dysregulated immunity and multiple-organ failure, making it virtually impossible to combat the infection. This syndromic response to infection can ultimately lead to septic shock, causing a dramatic drop in blood pressure and changes to cellular metabolism – essential processes in the cells.
The earlier sepsis is identified and treated, the better the outcome for the patient and the lower the cost to the healthcare system. Yet, at present, the diagnosis of sepsis is extremely slow. For every hour that the illness is left undetected, the mortality rate increases by 8 percent. In order to tackle the challenges of sepsis, we need to unpack the current issues surrounding its diagnosis.
Sepsis Diagnosis: Losing Vital Details in the Race Against the Clock
The existing practice of diagnosing sepsis not only lacks specificity, but requires multiple assays, is time consuming and resource heavy. In addition, there are often delays in diagnosis and treatment while waiting for results, leading to potentially worsened outcomes. Relying on broad physiological parameters and lab-based cell cultures which are used to pinpoint underlying infections, doctors order a battery of laboratory tests. These include hematological tests such as the Complete Blood Count (CBC) and inflammation markers to try and identify the source of inflammation and its severity. The CBC test, critical for diagnosis, requires a laboratory with expensive equipment that is operated by a trained professional, which is what makes this process both costly and time-consuming.
A Deep-dive Into Specialty Pharma
A specialty drug is a class of prescription medications used to treat complex, chronic or rare medical conditions. Although this classification was originally intended to define the treatment of rare, also termed “orphan” diseases, affecting fewer than 200,000 people in the US, more recently, specialty drugs have emerged as the cornerstone of treatment for chronic and complex diseases such as cancer, autoimmune conditions, diabetes, hepatitis C, and HIV/AIDS.
To add to the urgency, sepsis is a fast-moving infection that can quickly evolve from mild and treatable to life-threatening. However, due to the laborious diagnostic process, it frequently goes undiagnosed until it is too late. Sepsis also manifests very differently across patients, with this variability and complexity making clinical identification and severity assessments even more challenging.
Another danger from lack of specific and immediate diagnostics is the over-prescription of antibiotics. Patient conditions can deteriorate as they wait for results, leading doctors to prescribe antibiotics to fight a perceived infection. Unfortunately, these antibiotics may not be appropriate for that patient’s specific bacteria, contributing towards anti-microbial resistance (AMR) and the evolution of “super-bacteria” that don’t respond to mainstream treatments. If a patient with sepsis is resistant to their given antibiotic, the outcome is fatal. Ultimately, there needs to be a solution that counteracts these challenges in a simplistic and user-friendly way.
Point of Care: Adopting a New Diagnosis Paradigm
Addressing all of these concerns, point-of-care (POC) technology steps in. Simplifying the needs of the diagnostic process by offering accessible and affordable clinical information to detect sepsis at a much earlier stage, using POC platforms can lead to timely intervention with appropriate therapeutics. The CBC, the most ordered blood test worldwide, gives doctors insight into the patient’s blood parameters and overall health status, and has a longstanding role in the diagnosis of sepsis. There is a critical need for a simple POC instrument to perform this analysis and provide real-time results, eliminating the delays associated with standard laboratory testing. Other valuable infection markers are becoming available at the point of care, such as CRP (C-reactive protein), PCT (procalcitonin) and lactate. Widespread availability of such tools would allow for timely and more accurate diagnoses, potentially saving many more lives.
There are numerous benefits to utilizing POC tests: they are easy to use and provide rapid results; they utilize small sample volumes; they improve workflow; they save subsequent visits to the doctor, as well as necessary follow-ups; they eliminate waste and keep costs low; there are few infrastructure requirements, making them applicable in a variety of settings; and they do not require specially trained technicians to operate them. They are also more resource-efficient, allowing labs to focus on more complex pathogens.
Utilizing POC testing for sepsis is a pragmatic solution for risk-stratification of new patients, helping physicians to prioritize those for treatment based on the severity of their condition. POC testing can further help guide initial treatment, as well as monitor progression of the infection and evaluate patient responses, providing overall improved and more targeted medical intervention. So why haven’t we already implemented this technology into our sepsis diagnosis process?
This question opens us up to various issues. Firstly, while there are multiple POC tests available in the U.S., not all are widely implemented. For example, tests for proteins in blood used for cancer diagnosis, or infection and inflammatory markers like CRP and PCT, even though these have shown to significantly reduce the use of antibiotics in Europe. Availability is one thing, acceptance and implementation is another.
With a constant drive to lower costs by establishing centralized mega-labs, decentralized testing, which has recently been recognized as critically important, has been abandoned. Point-of-care testing has long been held back by regulatory concerns that prevent certain POC tests, such as the CBC, from being conducted outside a lab environment. This conservative approach does not acknowledge that the benefits of POC hematology far outweigh the risks, and even more so with recent technological advancements, which make POC testing even more robust. In addition, POC testing offers numerous longer-term benefits that will not be immediately evident, such as reducing antibiotic overuse and consequent drug resistance, as well as the cost savings of being able to test and treat rural patients in their own communities.
With technological innovations making POC testing more reliable and accurate, it is time to start looking closely at the resulting benefits. These developments alone should shift the decade-old opposition to conducting tests outside of the conventional laboratory setting. As technology continues to advance, POC testing must increase. Healthcare resources, already strained, have been stretched to almost breaking point during the current global pandemic, and near-patient testing will play an even greater role in helping patients get treatment efficiently.
While it is widely recognized that early detection of sepsis and timely treatment will decrease mortality, improve patient outcomes and decrease the length of stay in hospitals, nothing has yet been done to effectively overcome these issues. It has ultimately become clear that improved diagnostic speed and accuracy can contribute to faster intervention with lifesaving treatments, such as the administration of appropriate antibiotics, while simultaneously limiting the misuse and overuse of antimicrobial agents. Implementing POC testing as the new norm for sepsis diagnosis is also a practical solution for risk-stratification of patients – helping doctors prioritize those most critical, guiding treatment by monitoring the progression of infection and evaluating patients’ real-time response to their given treatment.
Accessible and immediate POC tests for sepsis biomarkers could improve healthcare access, reduce costs, minimize suffering for patients and, ultimately, contribute towards overcoming this global health crisis. The real question is, what are we waiting for?
Avishay Bransky, Ph.D., CEO and co-founder of PixCell, is an expert in microfluidics, with extensive industrial experience in applied physics, software and systems engineering. He is one of the inventors of the Viscoelastic Focusing technique, cell analysis methods and the microfluidic based cartridge. Dr. Bransky holds a B.A. in Physics, B.Sc. in Materials Engineering, and a Ph.D. in Biomedical Engineering, all from the Technion Israel Institute of Technology.
