Current evidence suggests it is a promising and effective option for patients with large prostate volumes, multiple comorbidities, young patient with erectile dysfunction from medications and suboptimal results from pharmacotherapy.

Larger, randomised studies with long-term follow-up data are needed for this technique to be formally established in the treatment paradigm for BPH.

Introduction

As men age, the prostate gland grows larger and may begin to press on the urethra. Enlarged prostate affects more than half of men by age 60 and causes symptoms such as frequent urination, weak urine stream and a persistent feeling of having to urinate. Surgery is the standard treatment for the condition but can cause complications such as sexual dysfunction and impotence.

A new non-invasive procedure could bring long-term relief from symptoms caused by an enlarged prostate. This new treatment is called Prostate Artery Embolization (PAE). This procedure works by closing the blood supply to the prostate and as a result, the prostate shrinks in size, causes less blockage, and the symptoms improve.

PAE Procedure History

PAE has evolved into an encouraging minimally invasive option for patients suffering from a variety of prostatic issues, including lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH), haematuria of prostatic origin, and prostate cancer. After initial medical therapy, transurethral resection of the prostate (TURP) remains the gold standard of surgical treatment. However, its role is undermined by the associated risks of bleeding and lasting sexual dysfunction. With the considerable prevalence of BPH and an associated impact on national healthcare in the UAE, less invasive options and minimally invasive procedures have been continually examined. Since first performing PAEs in 2008 in the world in Brazil, the multidisciplinary team at the University of Sao Paulo has been encouraged by patient outcomes. Al Ain Hospital has been offering PAE since 2015and over 25 patients with BPH have been treated.

Prostate Artery Anatomy

Technically, PAE is challenging. Knowledge of anatomical features to identify and catheterise target arterial branches is paramount to achieve the best clinical outcomes. Unnecessary catheterisation increases procedure time and radiation exposure. The prostate receives its arterial supply via the medial and the capsular/lateral branch but is variable among patients.

Assis et al proposed an angiographic classification of prostate artery anatomy and analysed 286 pelvic sites to find that most inferior vesical arteries and their prostatic branches arise from the internal pudendal artery. Cone-beam computed tomography (CBCT) angiography has been utilised to evaluate the many variants of the prostatic artery. With direct contrast injection and three-dimensional angiogram, subtle prostatic feeders are better identified when compared to digital subtraction angiography (DSA) and CT angiography.

Transfemoral Access vs Transradial Access

Traditionally, PAE has been performed via a transfemoral approach (TFA) but transradial approach (TRA) for PAE has garnered increased interest recently. Evidence has suggested that TRA results in shorter post-procedure hospital stays, decreased access-site complications, and an improved patient satisfaction. This method would also allow patients to ambulate immediately post PAE, which could facilitate urination. The distance from the forearm to pelvis along with the arterial tortuosity and previously mentioned variant anatomy has deterred initial attempts for PAE via TRA. Further, prior to selecting TRA patients, collateral circulation must be adequate as determined using a Barbeau test (ie, a modified Allen’s test with a pulse-oximetry device). Studies showed when PAE is performed via TRA, patients don’t need pre-PAE pelvic angiograms and have decreased procedure times, fluoroscopy times, and total radiation doses when compared with PAE through TFA. The exclusion criteria for TRA-PAE has been patient height (>6 ft), type D Barbeau waveform, and radial artery diameter <2.0 mm.

Indicated Patient Populations

One of the most promising benefits of PAE has been its efficacy in a variety of patient populations. PAE has been performed in patients with both small and large prostates. TURP in larger gland sizes, especially in prostate volumes >80 cm, is associated with longer operative times and an increased risk of bleeding and anaesthesia-related complications. In contrast, PAE has been demonstrated to be safe and efficacious in varying prostate sizes with no major complications. Further, PAE has demonstrated its role in elderly patients (≥75 years old). In a prospective study done by Wang et al, despite this cohort of patients having a higher prevalence of hypertension, heart disease, chronic obstructive pulmonary disease, urinary retention and antiplatelet agent use than younger patients, they experienced no major complications and a significant improvement in International Prostate Symptom Score (IPSS) after PAE. Conversely, TURP has been associated with an increased risk of complications in patients with multiple comorbidities.

PAE and Lower Urinary Tract Symptoms Due to Benign Prostatic Hyperplasia

In terms of symptomatic improvement in patients suffering from LUTS, PAE has continued to demonstrate its value. Most recently, a meta-analysis by Cizman et al examined PAE in the setting of short- to mid-term follow-up. Over 500 PAE patients were assessed to determine the efficacy and safety of the procedure. At 12 months, IPSS and quality of life (QOL) score decreased by 59 per cent and 56 per cent, respectively, with no significant change in International Index of Erectile Function scores. Prostate-specific antigen (PSA) level and postvoid residual (PVR) volume had the largest decrease within the first six months after PAE. Peak flow rate also increased by more than 90 per cent at 12 months. The analysis suggests that the degree and rate of morbidity associated with PAE is more favourable than that of TURP. When compared with adverse events of TURP, PAE has a lower incidence of bleeding, blood transfusion, UTI, and urethral stricture. PAE has also been demonstrated to have a minimal association with ejaculatory and erectile dysfunction when compared with TURP.

Medium- and long-term outcomes post PAE were recently analysed by Pisco et al; 630 patients were examined at 18 to 78 months. Medium-term follow-up was defined as 18 to 36 months and long-term follow-up was defined as 36 to 78 months. Long-term follow-up patients had a 76.3 per cent success rate with a lack of sexual dysfunction or urinary incontinence. The study noted that most clinical failures occurred prior to 18 months post PAE. As time post-PAE increased, the incidence of clinical recurrence decreased. Among all patients, there was a mean improvement in IPSS, QOL, and erectile function at both medium-term and long-term follow-up. Correspondingly, there was a decrease in prostate volume and PSA during these time frames. At Al Ain Hospital we have seen patients improving within days of the procedure and some of them weeks and one patient took one month till he was able to remove his catheter.

PAE and Haematuria

Prostatic haematuria is usually associated with BPH, iatrogenic urological trauma, or radiation therapy. Traditionally, it is treated conservatively with increased fluid intake, indwelling catheterisation with bladder irrigation, and medical therapy. However, when these interventions fail, refractory haematuria is life threatening. PAE has been shown to be an option for these patients. Although distinct prostatic haemorrhage is rarely seen on angiography, PAE is successful by obtaining complete arterial occlusion. By utilising a super-selective approach, control or cessation of haematuria within 1 to 3 days is achieved in 83 to 100 per cent of patients.

PAE and Prostate Cancer

After skin cancers, prostate cancer is the most common cancer affecting men in the U.S. Patients with advanced prostate cancer can present with or develop gross haematuria, urinary obstruction, and ureteral obstruction. Conventionally, this is treated with hormonal and other pharmacologic therapy. In refractory cases, surgical interventions have been performed. Although a large-scale trial has not yet been performed, PAE may play a role in the treatment of prostatic haemorrhage related to advanced prostate cancer.

Increased prostate volume has been associated with an increase in urinary complications post prostatectomy. In this sense, PAE may serve as a bridge to decrease prostate size and improve symptoms prior to prostatectomy or other surgical options.

Possible Complications

Although minimal, PAE has adverse effects post procedure. For patients without indwelling catheters, urethral burning during voiding and frequent urination have been the most common symptoms after PAE. However, these effects usually resolve within a week and can be treated with non-opioid analgesic medications. More serious complications are associated with non-target embolization to the bladder, rectum, and penis. Ischemia to these organs is always possible and must be avoided through proper mapping via CBCT, microcatheterization for distal embolization, and calibrated microspheres for predictable embolization. At Al Ain Hospital we experienced three complications, which resolved within few days. One patient had penile 3mm ulcer, which was treated by focal antibacterial cream (Fucidin), a second patient had hematospermia, which resolved in two weeks and the last patient who was 54-years-old experienced trash foot from cholesterol emboli two days after the procedure and doppler ultrasound showed patient arterial tree with all run off and the foot improved by conservative management by giving aspirin 100mg daily.

The Future of PAE

PAE is a novel and promising therapy and it has proven to be effective in treating BPH in symptomatic patients regardless of the size of the prostate and we have seen an increase in the number of self-referred patients coming to interventional Radiology clinic looking for this procedure as they might have heard and read about it and wanted to avoid surgical options if possible. The latest results of PAE are similar to surgery but with fewer complications and patients are getting discharged within three to six hours after the treatment, with almost immediate symptom relief.

I believe PAE could eventually become standard treatment for enlarged prostate. It must be continually investigated in order to validate these encouraging observations. Future larger studies with long-term follow-up along with randomised control trials are currently underway. Although current data suggest that PAE is a promising procedure for interventional radiologists, a concerted effort to include a multidisciplinary team of urologists, diagnostic radiologists and interventional radiologists will provide patients with optimum care.References available on request.

As a fifth-year medical student in the mid-nineties at one of the oldest medical schools in the region in Baghdad (founded in 1927), walking the corridor to the first practical session in neurosurgery, I was trying to remember the different branches of the circle of Willis as well as the names of cranial nerves. I was expecting a question or two on that in my first encounter with my eminent professor. The last thing on my mind was innovation, more importantly I was thinking about if my tie was in the right position, if my white coat was ironed and my shoes were clean. As my group and I gathered around one of the best neurosurgeons at that time, Prof. al Khalili, his first question after raising a hand-held ophthalmoscope was “Does anyone know who invented this?”. All seven of us were dumbstruck as to why would that be important. That routine continued all the way through the two weeks we spent with him, stopping at every instrument and every peculiar disease name to ask the same question – who invented it or who named that disease.  

As it turned out, it was Hermann von Helmholtz, who invented the ophthalmoscope (or rather reinvented its usefulness) – a simple genius technology that revolutionised the discipline of ophthalmology. A few years later, I asked Prof al Khalili about that habit of his and he said that he believed that knowing who invented the medical tools that we use helps us save or improve the lives of the patients we serve, “it is a must to improve and invent new tools to be able to help more”. In essence he said that innovative thinking is a core principle of being a good doctor. As it turned out Prof al Khalili had a very interesting career, holding a double fellowship from the Royal College of Surgeons and Ophthalmologist and had four inventions for global surgical tools to his name, in addition to being a linguist and a writer.

I was delighted with the theme of this year Arab Health this year – Innovation in healthcare. The new generation, population habits and behaviours are ever more globalised in aspiration and attitude, and patients today have higher and higher expectations. Also, with longer life expectancy and the chronic disease burden getting larger, and technology around us is forever expanding, therefore innovation is currently the only answer in town. Many of us mix innovation and invention most of the time. Actually, while invention is a completely new idea or product, innovation is a much wider concept. The dictionary defines innovation in so many different ways, but in principle it can be a new methods, ideas or principles, but also it could be a break with tradition, a shift of emphasis, a departure or a change in direction.

On the journey of thinking about what innovation is needed to tackle the many issues that healthcare in general and in the region specifically are facing, it is worth learning about the past first. In the words of the late Sheikh Zayed (PBUH) “He who does not know his past cannot make the best of his present and future, for it is from the past that we learn.”

The Arab, Islamic civilisation and this region has given so many innovations to the world; innovation that we still use every day to treat patients. If you walk into any surgical theatre today, and the chief nurse pulls the drapes to reveal a set of 20-30 oddly shaped shiny surgical instrument, they can tell you which ones are from about a thousand years ago.

In the 10th century, the Muslim scholar Al Zahrawi (also known in the west as Albucasis), produced his masterpiece al-Tasrif, which is a medical encyclopaedia that includes beautifully illustrated treatise of many of the surgical instruments that we use today. His efforts have positively impacted millions of patients across the centuries and across the globe to this day. In the words of the 19th century French historian Leclerc, “Al-Zahrawi remains a leading scholar who transformed surgery into an independent science based on the knowledge of anatomy. His illustration and drawing of the tools is an innovation that keeps his contribution alive.”

If you are a surgeon, then it is worth exploring the works of a Al Zahrawi, Ibn Zuhr and Al Razi. Abu Baker al Razi will be of particular interest to those of us who think of fighting infection every day; his systematic approach to making the environment in terms of hospital location, layout and materials work for the benefit of the patients and is still widely used today. If you are an oncologist, then the early ideas of describing cancer by Ibn Sina (Avicenna) and its grading was revolutionary at the time. If you are an ophthalmologist, then you should be thankful that Ibn Al Haytham revolutionised the science of lights and optics – his inventions are still lighting our way!

Finally, we all know from our medical school years that the blood circulation was meticulously described by William Harvey in 16th century Europe. However, it is widely accepted now that another Arab scholar described the pulmonary circulation 500 years earlier. Ibn Alnafis critically examined Ibn Sina (Avicenna) another intellectual, through the book entitled “commentary on the anatomy of the canon of Avicenna”. In this book, he described in detail the role of the lungs, its pulmonary circulation and dispelled the myths surrounding that subject. All of the above and many more had the courage and the conviction to challenge the status quo. They innovated for the sake of their fellow humans and their contributions are still creating an impact all over the globe. They clearly show that the skills of innovation are not dependent on who you are, where you live and what level of knowledge you have. They and many others from around the world observed, identified a pain point and were set on finding a solution that changed our perspective.

Many of us that are gathered today at Arab Health have seen medicine and healthcare changing beyond recognition in the lifetime of our career. The older generation still remembers the first half of the 20th century, when people used to have a life expectancy of almost half of what we expect today. Innovation in antimicrobial through the work of Fleming, vaccination through the work of Jenner, the focus on quality through the teaching of Deming, the surgical checklist by Gawande Et al and the multidisciplinary approach has moved the medical profession at a pace that many of us feel out of breath just trying to catch up. It is fair to say that instead of having healthcare that is simple but ineffective, nowadays we have an effective but complex healthcare that is constantly changing.

Looking into the future, we need to learn about the new tools that our fellow humans made available to us. While we focus our innovation efforts as a trade on inventing new drugs, new devices and new pathways, IT engineers and innovators have been advancing at a literally lightening or “quantum” speed. The advancement in big data farming, blockchain, artificial intelligence, IoT, social media and pixelated resolution is not only going to knock on our doors soon, rather it will be like a tsunami that will change everything we do. The advice to my fellow colleagues is to start learning and collaborating within the profession and outside on how to ride that tsunami and ride it effectively and safely for the benefit of the people we serve. Taking the example of Artificial Intelligence, a technology that is having the perfect storm to realise its full potential. A technology that with the advancement of data processing speeds, the availability of big data storage solution and expertise in algorithmic thinking will make some of our relied-on-specialties redundant.

While your 5-year-old daughter knows and can sense when you are angry, and a 5th year medical student knows how to be gentle on breaking bad news, they both might fail at spotting a T12 fracture in an X-ray of a patient with pneumonia. An AI will be really bad at breaking bad news, but they will surely spot that fracture. My anticipation that the biggest specialties that will be affected by this initially are radiology, histopathology and physicist. It is pretty much, any specialty that rely heavily on regular set of data that will be the first to change. The key word here is something that got drilled into me during my early years of medical vocation; “Pattern Recognition”.

Now preparing for these innovations and having an open critical mind and patient centred approach to solution are necessary.

We also need to learn that change is inevitable. Innovation is all around us and as we are gathered under the Arab Health banner in the UAE that has a very clear vision of how to be a positive force for the good of humanity, with a prime example of being the first country to have an AI minister.

I urge you to get out of your comfort zone and think critically on our current practices and start collaborating to push new ideas forward. Your patients, your families and your fellow human needs you.  

As we look forward to the next 20 years, we are proud of the impact we have had on the quality of care provided in both accredited and non-accredited organisations. However, despite our good work, we also recognise that there is still much more to do.

The JCI International Patient Safety Goals identify six key areas that are especially challenging for healthcare organisations:

Goal 1: Identify patients correctly

Goal 2: Improve effective communication

Goal 3: Improve the safety of high-alert medications

Goal 4: Ensure safe surgery

Goal 5: Reduce the risk of healthcare-associated infections

Goal 6: Reduce the risk of patient harm resulting from falls

Addressing these patient safety challenges is a central component of the JCI survey.  The JCI standards and survey help HCOs improve on reducing infections, falls and ensuring safe surgery. But healthcare organisations everywhere continue to struggle with these and other patient safety issues. Accreditation provides a solid foundation for managing the risks to patients. Our experience has shown that accredited organisations perform better in many areas of care. But we also know that accreditation does not mean zero harm to patients.

Today we are challenging healthcare organisations to imagine a state of zero harm to patients. We are studying the traits of highly reliable organisations (HROs) such as nuclear power and aviation to understand what healthcare can learn from these industries. These industries share the risk and complexities of HCOs but perform at much higher levels of quality over long periods of time.  

We have learned that HROs have strong leaders committed to reaching the highest levels of quality possible. These leaders create a culture that is both safe and just, meaning that staff feel safe to report opportunities to improve processes that are risky to patients. It also means that leadership sets clear boundaries about acceptable and unacceptable behaviours for all staff.

Highly reliable organisations understand that human error is inevitable. Memory lapses, distractions, interruptions, stress and fatigue impact employee’s performance. They reject the commonly held belief in healthcare that great, error free clinical care comes solely from professional training and hard work. They also reject a culture that keeps failures a secret.  HROs see actual mistakes, and equally important, near misses as valuable information, providing insight into where they need to work on improving work processes to mitigate the human factors.

Once an organisation knows where the process problems exist, there are many tools available to help improve these processes. Common process improvement tools come from manufacturing and include the tools of lean and six-sigma. The Joint Commission’s Center for Transforming Healthcare Care has developed Robust Process Improvement or RPI as a performance improvement model that tailors and augments these tools for the healthcare setting. At JCI we use the RPI model to drive our own performance. We have made this the way we work.

The major challenge leaders face in improving quality and organisational performance   is the change management necessary to move the organisation forward. Changing an organisation’s culture as well as changing the way work gets done is always met with resistance from the employees impacted. Organisational culture change means virtually everyone will feel the change. Specific groups, perhaps, are impacted more depending on what operational and clinical processes are undergoing change.

Why is change so hard? And how do leaders overcome the resistance to change? An article from the Harvard Business Review by Elizabeth Kantor Ross provides a top 10 list of why we avoid change. Some of the reasons cited include the fear of losing control, the fear that change is happening too quickly, the uncertainty that comes with change, the potential loss of status and worry that change will mean more work.

Leaders need to spend time on understanding why their staff is fearful of change and then address those fears. Transparency and honesty are important if the change is to be successfully managed. Good leaders begin the process with introspection into their own fears and concerns. They need to make a long-term commitment to implementing change and demonstrate that the change is a new way of working and not a new programme. They need to earn the trust of their employees by behaving as they expect all the staff to behave. They need to show authentic empathy in addressing the concerns of their staff. Anything less breeds cynicism which leads to inevitable failure.

This is all very hard work. It requires focus and discipline over long periods of time. But if done well, it opens the possibility of imagining a time when there is zero harm to patients.

Bachir Awad, Vice President and Managing Director, Cerner Middle East & Africa tells Daily Dose: “Motion Health over the last few years has been a major focus of ours on the innovation front. The technology uses Artificial Intelligence (AI) through videography, for instance, where a patient is able to stand in a room, and do various motions for a clinician but at the same time through cameras and technology, we are able to monitor every single movement and then come back and make a clinical assessment and recommendations, as to what potentially maybe wrong with the patient and what can be done to remedy it.

“Cerner has pioneered that space with our technology partners through various clinically developed materials that have been developed around it. We are actually quite confident that it is a solution that is ready for the market and has the ability to be able to diagnose diseases of today and potentially be able to prevent the diseases of tomorrow. Even at our booth, we are putting the spotlight on the innovation of tomorrow.”

Cerner has always been an innovative company, Awad highlights, and its focus has always been on ensuring better healthcare outcomes. The company wants to continue to create smarter systems that inform through data, as he stresses that it should be able to provide information that not only the physician can consume, but also what the consumer can use.

“We have got our next-generation platforms around Big Data and Population Health and these inherently have very sophisticated AI algorithms built into it and these systems can determine what’s happening to you as a patient based on the data it has,” he explains. “When data starts to inform decision-making and starts to predict that’s when you get better healthcare outcomes. AI has a big role in how we leverage technology. I think the future of AI could actually speak back to the user and be integrated with medical records, that to me is the next evolution of personalising healthcare.”

Awad emphasises that over the years, Cerner has been focused on how its systems can be delivered at a lower cost and at a faster pace. Ultimately, Awad shares that the company is trying to build efficient, lightweight systems that are not only smart but are also more intuitive and easier to use, but behind the scenes, they are much more agile thereby making them more efficient.

Furthermore, Awad believes that the UAE has been one of the biggest advocates of innovation and is striving to be an innovative country. From that perspective, he says, it’s great to see that theme come into healthcare. Awad concludes: “Cerner has been in the industry for 40 years; it’s a home-grown organisation and we have organically grown through innovation. So, innovation is in our DNA. We love to see our clients wanting to innovate and for us to be able to bring that innovation here to the UAE and to also be able to develop different things through collaboration with our partners here in the UAE and elsewhere in the Middle East. Being able to bring these innovations to the market that are unique and co-developed is definitely a privilege.”

There is a solid rationale for the use of TIVA in some patient cases where the delivery of inhaled anaesthetics is impossible or disadvantageous, or in scenarios where traditional anaesthetic delivery systems may be unavailable or impractical. In other cases, the use of TIVA could make the process more efficient and advantageous for the patient.

In recent years, TIVA has become more popular, practical and possible due to two main reasons – firstly, the pharmacokinetic and pharmacodynamic properties of drugs such as Propofol and newer short-acting opioids, which make them suitable for intravenous administration.

Secondly, new concepts in pharmacokinetic modelling coupled with advances in the technology of infusion pumps, which allow the use of algorithms such as Target Controlled Infusion (TCI).

During these last years, the cultural passage operated by the anaesthetists from manual infusion to TCI for the delivery of the drugs has been fundamental.

From manual control infusion to target control infusion  – there are different ways to perform TIVA.

M.C.I. (Manually Controlled Infusion): Manual infusion of boluses

Manually controlled infusions at a constant rate

T.C.I. (Target Controlled Infusion):

Plasma T.C.I.

Effect site T.C.I.

In the first way when we deliver, repeated for example, propofol boluses 0,3 mg/kg/min for 10 minutes, we will have:

After 3rd – 4th minute: effect site concentration between 1,2 and 1,6 µg/ml (sedation); —but after 10th minute: effect site concentration 4 µg/ml (hypnosis).

In other terms repeated boluses of drug determine a progressive increase of the plasma and the effect site concentration of the drug.

The second way is:

M.C.I: Manually Controlled Infusions at a constant rate.

Unfortunately, this has two main problems:

A constant i.v. infusion rate results in a progressive increase in drug plasma and effect site concentration.

The same continuous infusion at a constant rate of a drug, determine very different effect site concentrations at steady state, in individual of different age, gender, weight and height.

T.C.I. (Target Controlled Infusion)

In comparison to traditional inhalation anaesthesia, the inherent benefits of TIVA via a Target Controlled Infusion (TCI) make it a more straightforward and user-friendly technique for the caregiver, while at the same time offering a faster and more comfortable patient recovery.

TIVA is purely an anaesthetic technique, when used in cases where post-operative pain management will be required, multimodal pain management strategies could be applied such as conducting regional anaesthesia prior to the TIVA for post-operative use to improve patient recovery.

It is an infusion technique for delivering iv anaesthetic drugs via computerised pumps. The software is programmed with pharmacokinetic models capable of maintaining the desired drug concentration levels in plasma (Plasma T.C.I.) or at the effect site (Effect Site T.C.I.) by varying the infusion rate. How? With a Pharmacokinetic model specific for each drug.

What is a Pharmacokinetic Model?

It is a branch of pharmacology dedicated to determining the fate of substances administered to a living organism. The substances of interest include any chemical xenobiotic as such pharmaceutical drugs, pesticides, food additives, cosmetics, etc. It attempts to analyse chemical metabolism and to discover the fate of a chemical from the moment that it is administered up to the point at which it is completely eliminated from the body. Pharmacokinetics is the study of how an organism affects a drug, whereas pharmacodynamics (PD) is the study of how the drug affects the organism. Both together influence dosing, benefit, and adverse effects, as seen in PK/PD models.

In this case is a mathematic model, which predicts the plasma concentration of a drug following a single bolus or infusion of variable time lengths.

Pharmacokinetic variables are:

I. The number of compartments where the drug is administered

II. Compartment “volume” (V1, V2, V3)

III. Exchange rate of drug between the various compartments (“K”)

The aim of the model is to establish:

The volume size of compartments (V1, V2, V3)The K drug exchange rate of compartments, including the side effect.

The clearances

This is achieved by comparing the variables of each patient (weight, height, sex, age). How?

A mathematical model, which describes the pharmacokinetic behaviour of the drug was incorporated into a computerised delivery system which enables the anaesthetist to achieve and maintain a target blood concentration of propofol or any other drug and to manipulate this at will.

Some Questions

Is TCI the final solution to the problems of TIVA?

Is it possible to further enhance the quality of TCI anaesthesia?

What do we need beyond the TCI?

T.C.I. One Principle Characteristic

Various pharmacokinetic models, for the same drug, are reported in the literature for major part of those used in anaesthesia.

What About the Future?

Open Loop Control

User applies an input to the system

The system performs output is generated

Close Loop Control

The BIS is the weighted average of three sub parameters that analyse the phase and frequency relations among the component frequencies in the electroencephalogram. It changes monotonically with increasing depth of anesthesia. BIS correlates well with the hypnotic component of anesthesia Electroencephalographic parameters can be used t0 control anesthesia automatically.

Closed-Loop Control Offers Patients Several Potential Benefits

Because of more frequent sampling of the control variable and more frequent changes to the rate of drug delivery than with manually delivered anesthesia, the stability of the control variable may be greater. At the same time, the dose delivered is customised to meet the exact requirements of each patient, thereby overcoming the problems of interindividual pharmacokinetic and pharmacodynamic differences and differing levels of surgical stimulation.

Recovery times and the risk of inadvertent awareness may thereby be decreased. The BIS has already been used for automatic control of propofol sedation. We wanted to know whether BIS could be used to provide clinically satisfactory anesthesia and developed a computer system for this purpose.

Compared generally to traditional volatile anaesthetic techniques, TIVA offers several potential advantages. These include reduced incidence of post-operative nausea and vomiting, reduced atmospheric pollution, more predictable and rapid recovery, greater hemodynamic stability, preservation of hypoxic pulmonary vasoconstriction, reduction in intracerebral pressure and reduced risk of organ toxicity.

Quality control of anesthesia has become very important, owing the evolution in peri-operative management. Changes in surgical conditions and patient populations make it more than ever essential to manage anesthesia in a fast, simple and safe way. Hereby, a wide spectrum of pharmacological actions (analgesia, hypnosis, and suppression of somatic and autonomic responses to noxious stimuli) are needed to control the general anesthetic state.

The ultimate goal when administering a particular dose of an anesthetic or analgesic drug is to obtain the desired clinical effect, for which a specific therapeutic concentration of the drug at the site of action (= the receptor) is required. Individual anesthetics gives a unique spectrum of pharmacological actions, so the concept of a common depth of anesthesia may need to be revisited to reflect the separate clinical components of the ideal anesthetic state. To reach these high standards of care, an optimal titration of both anesthetic and analgesic drugs is required. Classically, opiates are used to manage nociception and short acting hypnotics are widely used to titrate the hypnotic component of anesthesia. However, by optimizing drug administration techniques, economics might become more beneficial for TIVA. Target controlled infusion might help.

In the nearby future, all sources of pharmacological and effect monitoring will be combined into anesthetic advisory and feedback systems enlarging the existing kinetic-based administration technology towards a total coverage of the dose- response relation. By measuring the patients’ individual response to a certain given drug dose, drug administration could be guided by a pharmacodynamic advisory system estimating the complete dose-response relation. Additionally, when technology is found to be validated enough, closed-loop technology could be used. Closed-loop systems are able to make decision on their own and try to reach and maintain a pre-set target. As a result, they might help the anesthesiologist in optimising the titration of drug administration without overshoot, controlling physiological functions and guiding monitoring variables.

References available on request.

Whilst many types of ACT in development show great promise, it is the CAR T-cell therapy has advanced the furthest, says Professor Stephen Mackinnon, from HCA Healthcare UK, who leads the bone marrow and stem cell program at University College Hospital in London. HCA Healthcare UK also has the unique distinction of being one of the first JACIE-IECT accredited private centres in the UK to offer CAR T-cell therapy under a commercial license.

“Conventional treatment for cancers like leukemia and lymphoma have generally involved the use of chemotherapy, sometimes with bone marrow or stem cell transplantation, but when these treatments fail, up until recently there had been no alternatives available. The result was that patients generally died of their underlying diseases,” says Professor Mackinnon.

However, the extensively trial-tested and approved chimeric antigen receptor (CAR) T-cell therapy is now shifting the landscape in cancer treatments. He explains: “Our T cells play a vital role in our immune system, orchestrating the immune response and killing cells infected by pathogens. On the surface of every cancer cell are specific antigens relating to that type of cancer.”

In CAR T-cell therapy, T-cells are collected from the patient’s blood and genetically modified in a laboratory over a two-week period, he elaborates. “These adapted cells are then re-infused into the patient and now have the ability to recognise specific antigens on tumour cells and eradicate them.”

Unlike traditional immunotherapy which usually refers to drugs used to stimulate or programme a patient’s immune system to see and destroy cancer cells, CAR T-cells are created from a patient’s own blood cells and engineered in a lab to be re-infused and recognise cancer cells, he says. “What makes it all the more exciting is that while chemotherapy targets all cells, including healthy cells, the receptors in CAR T-cell therapy are attracted only to the targets on the surface of the tumour cells.”

A small amount of chemotherapy is given when the CAR T-cells are put back into the patient’s bloodstream, but this is very minimal and is designed to allow the new cells to work properly, he further elaborates.

The process, explains Professor Mackinnon, is fairly simply and involves an apheresis procedure to isolate and collect a patient’s T-cells. These T-cells are transported to a laboratory where they are engineered to express CARs that recognise cancer cells. These modified T-cells are then grown and expanded within the laboratory. At the time the patient is scheduled to receive them, these modified T-cells are reinfused to the patient following a course of conditioning chemotherapy.

CAR T-cell therapy is not an extension or improvement of an existing treatment, he asserts. “It is a first-of-a-kind therapy that has the potential to revolutionise the approach to cancer treatment. CAR T-cell therapies are a breakthrough treatment for many patients, offering a highly successful, well tolerated treatment option where previously there may have been none. Patients receiving this therapy show a rapid and durable regression and remission and that we haven’t observed in other recognised treatments.”

Currently, the CAR T-cell treatment is available for both children and adults with Myeloma, Acute Lymphoblastic Leukaemia and Diffuse Large B-Cell Lymphoma.

Although CAR T-cell therapy is currently not a first line treatment now and is only given when people have failed conventional therapy, Professor Mackinnon hopes that in the near future, it will be able to treat other forms of cancer including breast, prostate and colon cancers. “CAR T-cell therapies seem to have a lot of potential, but further research is needed to make them mainstream and available to patients globally,” he says. “Many labs around the world are currently testing these therapies, not just for blood cancer but also for solid tumours such as pancreatic and brain cancers. Given the amount of interest the field has generated among researchers worldwide, it is likely that the next decade will be transformative in defining the cancer treatment paradigm.”

He adds: “At HCA Healthcare UK, initially, we will be accepting referrals for patients with Diffuse large B-cell lymphoma and are preparing to accept referrals for other types of blood cancers soon.”

As a first-time participant at Arab Health 2019, HCA Healthcare UK is connecting with healthcare providers and physicians across the UAE and in the region to introduce them to this new mode of cancer treatment.

Miroslav Kafedzhiev, Vice President and General Manager, of Honeywell Safety & Productivity Solutions (SPS) for Middle East, Turkey, Central Asia and Africa (META) told Daily Dose: “Integrating infrastructure and disparate systems to enable better care, Honeywell works with state-of-the-art healthcare facilities across the region to ensure the rapid flow of information for more agile operations.

"The company also specialises in workflow automation and communications to help reduce errors and increase productivity for clinicians, while improving the health of patients through effective monitoring in the hospital and beyond.”

Recently, the company implemented an advanced infant tracking solution at a large private hospital in the Middle East. The system provides a special service level to parents who want to track the identity, activity and movement of their newborn babies, to ensure the highest level of safety and care.

Kafedzhiev said: “Advancement in software and mobility technology has helped enhance patient care and healthcare delivery in a big way. The region is witnessing a lot of demand with regards to healthcare innovation, owing to several factors, including a rise in chronic diseases, increase in medical tourism demand and a swift shift towards digital transformation. Hospitals are tasked with doing more, which means leveraging the latest technology to provide the best quality patient care and ensuring an excellent patient experience.

“Experts and healthcare professionals are exploring ways in which blockchain and Artificial Intelligence (AI) can contribute to better care. We have already started to see positive signs of what is to come with these new technologies and believe that they can go a long way in improving everything from workflow automation and asset tracking, to facilitating more efficient clinical operations.”

The GCC healthcare market is growing rapidly and is expected to reach US$ 94 billion in 2021, witnessing a considerable growth of 8.7 per cent annually from 62 billion in 2016, according to a recent report by MENA Research Partners (MRP). According to Kafedzhiev, the UAE healthcare industry, specifically, has evolved rapidly in the last few years, fueled by technological innovations as well as huge investments by the government. With the government heavily focusing on tapping into medical tourism and becoming the regional hub for healthcare, he foresees continued growth in the sector.

“We anticipate data analytics to continue to be a major trend in the industry, with it being leveraged to provide better services to customers at every touch point,” he emphasised. “Hospitals and clinics will also continue to provide customised experiences to patients, while creating a comprehensive range of online services for them to choose from. These trends will not only ensure improved workflows, and streamlined processes, but will drive further growth of the sector.”

Kafedzhiev concluded: “Quality healthcare is vital for a prosperous society, and we are committed to supporting healthcare providers in their quest to provide superior care to patients. We continue to be focused on delivering advanced hardware and software solutions that ensure enhanced patient care and experience, higher clinical value and more operational efficiency, which all contribute to the continued transformation of the healthcare industry.”

At Arab Health, Honeywell (located at Z3.B09) is showcasing its Intelligent Lifecare Systevo portfolio that integrates nursing workflows, clinical communication, mobility and care specific apps to ensure a safe, clinically efficient, and smooth patient experience. Other technologies include high-performance specialty equipment, such as printers, barcode scanners and wristbands, aimed at improving patient safety and driving productivity across the hospital.

The result is that many patients, adults and children, still have debilitating seizures. Among this subset of patients, many also suffer from cognitive dysfunction, depression, accidents, and medication side effects, in addition to Sudden Unexplained Death in Epilepsy (SUDEP).

The International League Against Epilepsy (ILAE) has defined drug-resistant epilepsy as the continuation of seizures or aura during a 12-month period, despite being prescribed two or more properly chosen, properly tolerated, and properly dosed medications. Multiple studies have shown that when patients are prescribed additional medications, they may become pharmacoresistant.

• Response with first drug—50 per cent

• Response with second drug—11 per cent

• Response with third or multiple drugs—4 per cent

Some predictors of pharmacoresistant epilepsy include high initial seizure frequency, neonatal seizure, over 12 years of age at onset, intellectual disability, abnormal exam and imaging, failure of first anti-epilepsy drug, or failure to respond in the first year of treatment.

A significant number of children do not respond to pharmacological treatment, resulting in a low likelihood of seizure freedom. The consequences of drug-resistant epilepsy extend beyond the seizures themselves, impacting quality of life and resulting in:

• Seizure-related injuries

• Increased healthcare utilisation

• Increased morbidity and mortality

• Depression, anxiety and sleep disturbances

• Cognitive and memory impairment

• Adverse effects of long-term anti-epilepsy drug use

• Increased risk for SUDEP

•Impaired social relationships and functions, including the ability to obtain education, work, drive and establish families

Multiple drugs also can cause adverse reactions for these children, hence the need for non-pharmacological treatments. And, despite the introduction of new anti-epilepsy medications, the incidence of drug-resistant epilepsy has not changed significantly over the past 20 years.

Surgical Options to Treat Drug-Resistant Epilepsy

Clearly, a wide range of treatment strategies may be necessary to help patients who have drug-resistant epilepsy. This is where surgery may be an important consideration. Surgical options include:

Epilepsy resection surgery: Most commonly, this surgery is used to treat temporal lobe epilepsy and involves removing a portion of the temporal lobe of the brain. Overall, in patients who are good candidates for a temporal lobectomy, more than 80 per cent will have a significant improvement in seizure control. However, most patients will need to continue taking anti-seizure medications. Over time, with the guidance of their epilepsy team, some of these patients may be able to lower the dose of the medication needed. Unfortunately, 10 to 15 per cent of these patients do not experience an improvement in seizure control.

Laser Interstitial Thermal Therapy: Minimally invasive techniques using laser heat ablation of epileptic tissue have resulted in similar seizure control outcomes in a number of different seizure types. During the surgery, an MRI is used to precisely map out the exact area of the brain on which to operate. The laser treatment is then targeted to this area to eliminate the seizure focus. All of this is done without needing to open the skull, making it a minimally invasive procedure.

This minimally invasive surgery can be effective for drug-resistant focal epilepsy due to small lesions and has been used most commonly in people with temporal lobe epilepsy from mesial temporal sclerosis. Early data on laser ablation surgery shows more than half of people treated will achieve freedom from seizures. This type of surgery continues to be carefully studied.

Neurostimulation: Three neurostimulation devices are approved for the treatment of drug-resistant epilepsy. These are vagus nerve stimulation (VNS), responsive neuro stimulation (RNS) and deep brain stimulation (DBS).VNS is approved for treatment of focal epilepsy when surgery is not possible or does not work. A small electrical generator is implanted under the skin over the chest. A wire, called a “stimulator lead,” is then attached onto the vagus nerve located in the neck. The generator stimulates the vagus nerve on a set schedule. Over time, this helps to reduce the number and severity of seizures a patient has. It is effective in over half the people who try it.

RNS is a device that can record seizure activity directly from the brain and delivers stimulation to stop seizures. The device, also called an electrical generator, is implanted in the skull. Electrodes are placed on or in the brain in the area where seizures begin. The device detects seizure onset and then delivers an electrical stimulation to stop the seizure.

DBS surgery involves implanting an electrode into the brain and placing a stimulating device under the skin in the chest. The brain electrode is implanted through a small hole made in the skull. Advance magnetic resonance imaging (MRI) and a computer navigation system are used to guide the electrode to the exact “target” position deep in the brain. The stimulator device placed in the chest is similar to a pacemaker and is connected to the brain electrode. The device sends signals to the brain electrode to stop signals that trigger a seizure. DBS surgery for treatment of seizures was approved by the U.S. Federal Drug Administration (FDA) in 2018.

The importance of early and proper diagnosis of epilepsy is critical to identification of the correct type of treatment, especially for those patients whose epilepsy is drug-resistant. Early intervention with the personalised proper method of treatment for that particular type of epilepsy has been shown to drastically increase success rates in controlling seizures, improve quality of life for patients and significantly reduce the risk of SUDEP.