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Stress: a biomarker of the patient’s quality of life

What a stress!” How many times have we thought or said this sentence in our life?

Stress is a reaction that occurs when a person perceives an imbalance between the solicitations received and the resources available; a real self-defense mechanism activated by our body to re-establish a new internal balance (homeostasis).

There are many stress factors that can come from real threats (cold, fatigue, a surgical operation, etc.) or imaginary ones (fear of flying, losing a loved one, a financial crisis, etc.). In the second case we particularly refer to anxiety, defined as the anticipatory phenomenon of a fear that is sometimes unjustified.

Several biological studies have proven that the body reacts to perceived stress, not to the one actually experienced; at the mere perception of a danger, the body begins to secrete stress hormones. If we are facing a ferocious animal, the body immediately reacts to a possible danger – being bitten – without actually knowing if the event will occur or not. The same happens when, for example, we avoid asking for a promotion for fear of being fired or we don’t invest our savings in the financial market fearing a collapse.

It is easy to understand that stress is not necessarily bad: there is in fact a good stress – called eustress – that allows our body to cope with small and large emergencies, giving us unexpected strength and endurance. But if the stressful situation lasts too long over time, and is not followed by a relaxation phase, it has repercussions in a series of adverse effects on the body. We then speak of bad stress, or distress.

The mechanism that regulates stress involves several organs in our body. The central unit of stress can be identified in the amygdala, a primordial nuclear complex in the shape of an almond located in the center of the brain. It is responsible for the upstream activation of the “fight or flight” system, which inhibits the brain structures involved in the most rational processes – hippocampus (memory) and prefrontal cortex (temporal and partial sequencing of information, evaluation of their relevance, qualitative/quantitative analysis of actions and their consequences) – and instead stimulates the hypothalamus to produce hormones.

Along the HPA (hypothalamus-pituitary-adrenal) axis, stress hormones push the adrenal glands to produce cortisol, adrenaline and noradrenaline (catecholamines). In moments of high tension, cortisol increases glycogenesis (release of glucose into the blood), providing the body with all the energy it needs (or thinks it needs). With the subsequent release of adrenaline and noradrenaline, an increase in blood pressure is finally achieved to improve physical performance and alertness.

Once the stressful situation has passed, the body returns to balance (muscle tone, breathing, heart rate and blood pressure decrease) and so it relaxes. This last phase is essential: without it, the conditions for burnout occur, which is the situation where the adrenal glands are no longer able to secrete the amount of cortisol required by the body until it runs out.

The level of cortisol produced varies throughout the day following a specific curve. Usually the highest peak occurs in the moment before awakening – in order to provide the body with the energy it will need – and then decreases later. Stress can affect this curve, forcing the cortisol level to remain very high even at the end of the day; this allows you to work late into the night, but hinders sleep and in the long run modifies the sleep-wake rhythm: in the morning you feel tired because cortisol levels are low, but increase throughout the day until reaching excessive peaks in the evening.

The patient suffering from chronic stress may experience memory and / or learning problems and are more likely to develop forms of atherosclerosis related to hypertension, cardiac arrhythmia and myocardial infarction. Furthermore, high levels of cortisol can weaken the immune system, increasing the risk of contracting inflammation and promoting the onset of diseases such as osteoporosis. Numerous gastrointestinal disorders, such as irritable bowel syndrome, are also associated with high levels of stress.

It can be said that stress is a real biomarker of the patient’s quality of life: when it increases in an uncontrolled way it can strongly affect our quiet life, exposing us to important symptoms and risks.

It is therefore very important, both for the patient and for the physician, to keep stress under control through its continuous monitoring and its complete evaluation in the treatment of diseases.

Through the iTwinSense mobile application, the patient can collect and share to their trusted physicians – in a safe and secure way – various data useful for identifying stressful situations. This information is part of the iTwinSense data ecosystem, a constantly updated and evolving database. No multiple or separate data sharing: our users simply choose the complete configuration of data to show to the physicians so that they can have an instant view on their platform.

Lots of stress related information can be collected – through mobile applications, smartwatches and wearable medical devices – such as heart rate, blood pressure, arterial saturation, nutrition and sleep analysis. Or through hospitals lab analysis like the levels of cortisol, adrenaline, noradrenaline, glycemia and triglycerides in the blood or other body fluids.

Several smartwatches on the market today provide the ability to monitor your stress levels through specific indicators. Although they may vary, in general, the score assigned to the individual is based mostly on the data recorded on the heartbeat.

In particular, statistical indices such as the “stress score” allow you to measure the Heart Rate Variability (HRV) which is fluctuation of the heart rate at rest, managing to detect variations of a few milliseconds. These oscillations are completely natural and due to the alternation of opposite impulses sent by the sympathetic and parasympathetic nervous system: the first serves to prepare the body for action by increasing the heartbeat, breathing and blood sugars, the second regulates the visceral function, lowers heart rate, respiratory rate and predisposes to rest. In a normal situation – when the body is not stressed – the two systems are in balance with each other and the result is a high HRV. On the other hand, when a low HRV is recorded, we are probably in an imbalance phase that could indicate an increase in stress levels.

All this information, also crossed with the results of aptitude tests and evaluation of the patient’s stress perception, could provide the pysicians with a broader framework for the diagnosis and treatment of different diseases.

Dealing with a more or less prolonged period of stress can have many negative consequences: wouldn’t it be interesting to have tools available to monitor it correctly and use it to our advantage? At iCareX, we are working on a new technology that will finally help physicians to improve the quality of life and use personalized treatments that take into account the patient’s stress.

In particular, through iTwinDiscover platform, the physician can evaluate – with the support of advanced clinical scenario analyses based on artificial intelligence – which are the most effective drugs for the development of treatments that can also be optimized on the basis of stress levels recorded by the patient. In this way, it will be possible to explore the expected effects of different treatment plans by opting for the treatment that minimizes the negative impact on stress and therefore on the patient’s quality of life.

The exploration of clinical scenarios through artificial intelligence – developed by iCareX – will be a “game changer” for personalized medicine starting from 2021. In the specific case of stress, this technology can allow healthcare professionals to develop treatments that are not exclusively aimed at eradicating the disease but also at preserving the general wellness of the patient being treated.

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