Women have unique risk factors for heart disease that need to be taken into account in prevention and treatment strategies, according to a Cleveland Clinic cardiologist who led a team tasked with updating recommendations on women and cardiovascular disease for the American College of Cardiology.

Traditionally, doctors have treated men and women as the same when it comes to heart disease, but the director of the Women’s Cardiovascular Center at Cleveland Clinic, Leslie Cho, M.D., says that it is time to start thinking differently.

She explains: “For years, we’ve thought about men and women as having the exact same risk factors, namely, high blood pressure, hyperlipidaemia, smoking, diabetes and family history. However, while heart disease is the number-one killer and most prevalent disease in women, women actually have a very low risk in terms of the traditional risk factors.

“However, some conditions specific to women, such as endometriosis, have been found to raise the risk of developing coronary artery disease – the leading cause of heart attacks – by 400 per cent in women under age 40.”

In compiling the updated recommendations, Dr. Cho and her team reviewed diseases that are more prevalent in women; sex-related differences in traditional risk factors; and risk factors that only women experience, such as those related to pregnancy.

Risks unique to women

In terms of pregnancy-related conditions, they noted that high blood pressure during pregnancy, gestational diabetes, preterm birth and miscarriages all increase a woman’s risk of developing heart disease. Identification of pregnancy-related conditions is important, says Dr. Cho, as it can help identify younger women, with low traditional-risk scores, to allow for earlier monitoring of cardiometabolic factors and management.

Hormonal conditions specific to women have also been associated with increased heart risk. One of these is premature menopause, defined as menopause before the age of 40.

Dr. Leslie Cho

Dr. Cho explains: “Oestrogen offers women some protection from heart disease until after menopause when oestrogen levels drop. This is why the average age of for a heart attack in women is later, at 70, as opposed to 66 in men.”

Another sex-specific risk factor is a hormonal condition called polycystic ovarian syndrome (POCS), found in one in 10 women. This is associated with cardiometabolic factors, which, in turn, are associated with increased heart disease risk. The cardiometabolic factors associated with POCS include abdominal obesity, abnormal glucose control and diabetes, elevated blood pressure, and abnormal amounts of fats – such as cholesterol – in the blood, known as dyslipidaemia.

Differences in traditional risks

Regarding sex-related differences in the traditional risk-factor category, it has been found that hypertension and diabetes are strong risk factors in women. Another risk factor, high blood pressure, is more common in women over the age of 50 than in men.

Woman are also more likely than men to experience depression or mental health issues, such as anxiety and chronic emotional stress, that can have an impact on their heart health.

“We really should be treating not just the blood pressure number, or the cholesterol number, but rather treating the whole patient, including their mental health, to have a good cardiovascular outcome,” says Dr. Cho.

She adds that studies have also shown sex differences in response to treatments, and doctors need to take these into account.

Common prevention strategies

Despite the different sex-related risks, Dr. Cho points out that there are common areas where either sex can lower their risk for heart disease by making changes to their lifestyles. Among these she includes avoiding smoking, getting regular exercise – at least a 30-minute walk daily – and maintaining a normal weight, blood pressure, blood lipid and blood sugar levels. She recommends a diet high in fruits, vegetables, whole grains and fish, and low in animal products, simple carbohydrates and processed foods.

The 2020 biosimilars market estimate for the MENA region was US$1.6 billion with a double-digit growth rate before the pandemic hit the world. However, as the gravity of the situation started unfolding, it became explicit that there would be a decline of about 6 per cent to 10 per cent from the original estimate. This decline is attributed to the international supply chain disruptions, nation-wide lockdowns, overwhelmed healthcare infrastructure, poor patient adherence for injectable products and delay in the approvals and commercialisation of new biosimilars in the region.

This decline will not cause long-term disruptions as patients requiring biological products have chronic conditions and their treatment requirement is for a lifetime. By mid-2021, the biosimilars industry is expected to get back on its original growth trajectory but around the contours of newer opportunities.

Prediction 1: Local production of biosimilars is expected to increase by 8-10 per cent in the next 3-4 years with government impetus, leading to more MNC-domestic collaborations

GCC countries such as the KSA and the UAE lead the local manufacturing initiatives and will continue to invest in greenfield manufacturing projects, especially for biosimilars. Favourable government policies (e.g., scrutiny of high-priced, exported branded drugs) and incentives towards R&D-intensive local manufacturing of monoclonal antibodies-based biosimilar drugs for rheumatoid arthritis, psoriatic arthritis and cancer will further boost the localisation agenda in the next 3-4 years.

With COVID-19 creating immense financial pressures on the payers, hospitals and patients, the government is looking for ways to lower healthcare costs and reduce out-of-pocket expenses for patients as a long-term strategy. Thus, it is expected that there will be faster reforms in the regulatory landscape that support the biosimilar category and the region will see growth in the number of local contract development and manufacturing organisations (CDMOs) and domestic manufacturing plants catering to the biosimilars market with potential drugs like adalimumab, rituximab, infliximab, etanercept and trastuzumab. It is recommended that drug OEMs prioritise choosing free economic zones and hotspot locations with maximum incentives to produce locally and team up with local pharmaceutical companies with high quality and technology standards. It will be critical for MNCs to strategically collaborate with local agents or distributors for expertise on domestic contacts, customs regulations, new laws and specific opportunities to localise their finished product manufacturing processes.

Prediction 2: Biosimilars offered with comprehensive patient support programmes will gain maximum traction in the region

With COVID-19 cases incessantly rising, the plans to return to normalcy loom under uncertainty, and patients’ dependence on medications, whether a biologic or biosimilar, to manage their chronic conditions is not going to slow down or stop. Several pharmaceutical companies are offering comprehensive and holistic support programmes for their patients, providing financial support (access) and other value-added services (assistance) like online consultations with doctors, in-home diagnostic support, home delivery of medicines, nursing support for in-home injections, transportation support and counselling support.

Frost & Sullivan research findings highlight that the brands with patient support programmes for access will observe an increase in prescription rate by 6 per cent; the brands with patient support programmes for assistance will see an increase in prescription rate by 10 per cent in the next 12 months. With biosimilars being introduced in the MENA region at 60 per cent of the price of biologic counterparts, we believe that integrating biosimilars with patient assistance programmes like telehealth, e-pharmacy and home nursing support would enable this segment to capture about 50 per cent of the total market share by 2025.

Prediction 3: Virtual interactions between pharmaceutical companies and physicians will be the new norm post-COVID-19

We believe that in the next five years, more than 60 per cent of physicians will prefer virtual interactions with pharmaceutical company representatives. One of the momentum shifts we are starting to see in the biopharmaceutical industry is the rigorous adoption of virtual collaboration tools for tele-detailing. Biopharmaceutical companies are currently working on prototypes that enable their medical representatives to interact and engage with physicians in a productive virtual environment. Companies are now adopting virtual collaboration tools for tele-detailing and supplementing them with social media platforms to inform and educate physicians in a more personalized manner. We see an immense opportunity for biosimilar companies in the region to leverage various digital channels like webcasts, webinars and virtual events to share the latest advancements in the biosimilars segment, like clinical data.

Companies that are preparing to launch new biosimilars in the MENA region in 2020 should plan for a soft launch and leverage digital tools and technologies for their marketing activities with the Key Opinion Leaders (KOLs). Companies with biosimilars in their portfolio should initiate discussions and training sessions for key rheumatologists, dermatologists, gastroenterologists, oncologists and other specialists in the country and transition them to digital portals as a long-term strategy.

Conclusion

Biopharmaceutical companies need to redefine their strategic business models and leverage digital technology to be a winner in the post-COVID-19 world. To succeed, all stakeholders across the value chain must collaborate and deliver a digitized patient-centric solution to truly address patients’ needs.

As part of the ongoing COVID-19 pandemic and the UAE government’s Stay Home initiative, Aster Volunteers launched the ‘At Home’ digital initiative across its social media platforms and is conducting educational sessions on health and wellness for those at home, particularly families.

Moreover, the #FeedTheHungry initiative is one where Aster Volunteers has partnered with NGO’s and restaurants in Dubai to provide food supplies to those who have been affected by the pandemic.

Dr. Azad Moopen, Founder Chairman and MD of Aster DM Healthcare, told Omnia Health Magazine: “We are proud to have delivered food packets and ration kits weighing 22kg each, which contain rice, flour, lentils, oil, sugar, salt, noodles, biscuits and dates, which can serve up to 314,489 meals as of 31 May.

“Each ration kit is enough to last a family of four for three to four weeks. The response to these initiatives has been extremely positive, especially through the #FeedTheHungry campaign where we have been able to offer support to families and individuals who have faced financial hardship as a result of COVID-19.”

Aster Volunteers is the global corporate social responsibility initiative launched by Aster DM Healthcare, in 2017 on the organisations’ 30th anniversary. It has a singular vision – to unite people from all walks of life in helping make the world a better place.

The initiative has impacted over 1 million people with over 27,401 volunteers in three years. Through the initiative, 290,986 individuals have been treated through mobile medical camps; 169,207 people have benefited from basic life support training, and 36,019 free surgeries, as well as health investigations, have been conducted. It has supported the recruitment of 114 differently-abled people and treated 533,146 people through 3,640 medical camps.

“We believe that this initiative will bridge the gap between people who would like to help those in need, and we welcome everyone to be an Aster Volunteer and make an impact on the lives of others,” said Dr. Moopen.

Supporting the community

Aster Volunteers has also launched a webinar series called ‘Break the Chain’ across its social media platforms, with the aim to address various topics related to COVID-19. The series is hosted by doctors at Aster where they address the most common concerns people have about the virus and share advice and insights on how to sustain oneself and families during this time. The Webinar series has reached to 450,384+ viewers so far.

The organisation has also channelised its WhatsApp platform along with NGO’s to create an outlet for people who have concerns and require counselling on the virus. Through this channel, a team of medical volunteers filter incoming messages and assist the person according to their query, and if needed they will be connected to a doctor via a conference call. On average the team has received and managed 15 to 20 calls each day.

Aster Volunteers also works closely with the Dubai Health Authority (DHA) by providing the Aster Mobile Medical Service to transfer patients via Dubai Cooperation of Ambulance Services from Aster’s various units to isolation camps and vice versa. The initiative has also assisted in COVID screening camps at multiple densely populated areas in Dubai, organised in collaboration with the DHA and Aster Primary Care.

Dr. Azad Moopen

“Times are tough, and this pandemic has affected millions around the world. But what we have also seen during this tough time is how many people have come together to support each other even in the smallest way possible. I believe that even the smallest act of help can have a big impact on the lives of others, especially those who have been directly affected. We do not need to be part of charity organisations in order to help, we can create our own community and have the same impact. We must remember that while protecting and helping others it is crucial to make sure that we, as individuals, are protected and in good health ourselves,” he said. 

Moreover, recently around 100 frontline medical professionals, volunteers, government entities and supporting organisations were honoured by Aster DM Healthcare and Consulate General of India for their relentless efforts over the last two months, which helped in the successful recovery of more than 1500 Covid-19 patients who were asymptomatic or mild to moderately ill. 

“As a healthcare organisation, we have been at the forefront of managing this crisis with our facilities and staff being actively involved in working with the government to control the pandemic. Most of the medical staff and volunteers who have been actively involved in managing this facility had volunteered to be a part of this project, putting their own personal safety at risk and they continued to work relentlessly for long hours every day to be able to heal each of the patients who came to them, following all necessary measures to control the spread of COVID-19. We are proud of their tremendous achievement and commend the work that they have done,” said Dr Moopen.

Patients in the UAE can now benefit from a single dose heated chemotherapy – Hyperthermic Intraperitoneal Chemotherapy (HIPEC) – which is used in advanced cases of abdominal cancer where tumours have spread to the lining of the abdominal cavity.

Rather than a series of intravenous infusions, HIPEC uses a single dose of chemotherapy drugs delivered directly to the abdomen. The drugs are delivered to the cavity following surgery to remove all visible tumours while the patient is still in the operating room. This method allows any remaining cancer cells to be destroyed, preventing them from becoming tumours.

“In some more advanced cases of abdominal cancer, patients may have hundreds of small tumours in their abdominal lining. While these can be removed with surgery, a strong, targeted dose of chemotherapy is needed to kill any cancer cells left behind. Not only are we able to deliver the drugs directly to the affected area, it only requires a single dose, minimising the side effects for patients,” says Dr Yasir Akmal, an oncologic surgeon at Cleveland Clinic Abu Dhabi, the hospital offering the treatment.

Effectiveness of chemotherapy drugs

To improve the effectiveness of the chemotherapy drugs, they are heated to 42 degrees, enabling them to penetrate deeper into the tissue, destroying more cancer cells. During the infusion, the patient’s body is gently rocked to ensure the chemotherapy drugs reach the entirety of the abdominal cavity. To ensure the patient’s body remains at a safe temperature, they are placed on a cooling pad during the procedure.

Following the single treatment, patients are admitted to the hospital for around 10 days while they recover. Once recovered, they can return to their lives under the close supervision of their care team.

Cleveland Clinic Abu Dhabi recently performed its first HIPEC procedure, with doctors anticipating performing a dozen more in the coming year. The introduction of the treatment comes as the hospital continues to expand its range of cancer services in advance of the opening of its dedicated oncology centre.

“The introduction of this new therapy builds on our range of surgical and clinical treatments for patients in the UAE with advanced abdominal cancers. It underscores our commitment to continuing to expand the range of oncology treatments and support services we offer, ensuring that we continue to meet the most pressing needs of our community while eliminating the need to travel abroad,” explains Dr Stephen Grobmyer, Chair of the Oncology Institute at Cleveland Clinic Abu Dhabi.

“Cleveland Clinic Abu Dhabi continues to innovate in support of cancer patients, adding to our existing range of state of the art medical and surgical treatments for cancer. When complete, our dedicated oncology centre will provide a centralised hub for our complete range of cancer care, enabling patients to benefit from a seamless journey through every step of their recovery.”

This article was originally published on Conexión Expo Med.

According to data from Unicef, the WHO, Gavi and Sabine Vaccine Institute, at least 68 countries have seen immunisation programmes disrupted, which could affect approximately 80 million children worldwide.

Related: Disinfection, sanitisation and cleaning: concepts of the “new normal”

The WHO reported that child immunisation services have been disrupted since March 2020. "Of the 129 countries for which data was available, in more than half (53%) there was disruption ranging from moderate to severe, or total suspension altogether, of vaccination services during the months of March and April 2020," said the organisation.

Disrupted and suspended immunisation formed the central discussion of the webinar “Vaccination at risk? Analysing the potential delays and continuity of vaccination programmes worldwide” at Omnia Health Live.

Related: Latin American health systems need reconfiguring post-pandemic

Barbara Saitta, medical advisor and promoter of vaccinations at Médecins Sans Frontières in the United States, assured that it has been difficult to continue with vaccination programs not only in Latin America, but in other developing countries. In addition, the medical adviser warned that if immunisation is stopped there may be catastrophic consequences.

Pablo Kuri, an epidemiologist, public health specialist  and former Undersecretary of Prevention and Health Promotion in Mexico, warned that one of the problems they have faced during the pandemic is that the health agenda has focused on COVID-19. "It is a great problem that we are facing, not only for vaccination, but for other diseases that have been neglected," added the public health specialist.

In addition, the epidemiologist pointed out that if vaccination is forgotten, great problems can arise within countries. If Latin American countries do not guarantee vaccination coverage, all those found in national programs, there is a great risk that diseases that have already been controlled will resurface.

In 2016, America had been declared free of measles. "Due to the lack of coverage, basically in Venezuela, we have the reintroduction of measles on the continent," added Kuri, asserting that good vaccine coverage guarantees the control of outbreaks. In Mexico there was an outbreak of measles that could be controlled in time: the 186 cases could have been more had an adequate vaccination program not been carried out.

Vaccination challenges during the pandemic

One of the biggest challenges of vaccination during the pandemic is fear. In Chile for example, people will not be vaccinated for fear of becoming infected with COVID-19, which has affected the desired number of immunisations and has given way to new vaccination strategies.

Jan Paul Wilhelm, pediatric infectious medicine doctor at the German Clinic in Santiago and a former member of the National Immunisation Technical Advisory Group (NITAG), told that in Chile the national immunisation programme is continuing to run and with a healthy budget. "It seems to me that the budget is more than 60 million dollars," he added.

While the system is working, people are refusing to go to vaccination centres or clinics because: "They are afraid of getting COVID-19 from going to these places where patients are," said Wilhelm. However, he also assured that conditions are safe for everyone.

A strategy used in Chile to immunise the child population is to reopen schools and vaccinate children in their cars. Wilhelm explained that in Chile children up to 10 years old are immunised free of charge.

Barbara Seitta noted that, previously, there was less distrust in vaccination, especially in developing countries, since the population of those nations saw the consequences of diseases preventable with immunisation.

Alfonso Rodríguez, vice president of the Colombian Association of Infectious Diseases in Colombia, warned that as COVID-19 has a wide spectrum of symptoms there are possibilities not only to confuse the diagnosis, but also of coinfections.

In Latin America there are other diseases that pose a great risk to the population, such as dengue, zika or measles. Coinfections have been reported in Mexico, such as “covidengue”: the combination of COVID-19 and dengue, which can have serious complications for infected patients.

Vaccination before the COVID-19 pandemic

In Latin America there were  barriers even before the pandemic: the harsh socio-political context that some countries experience, such as poverty or forced migration.

Alfonso Rodríguez explained that forced migration can carry diseases from one country to another and bring serious consequences. While countries like Brazil and Colombia began to face the pandemic were still dealing with measles outbreaks imported from Venezuela.

Concurrent diseases or epidemics are known as a snydemic. “This concept implies the concentration of two or more epidemics that occur in the presence of temporal or geographic factors added to social conditions," Rodríguez explained.

Unfortunately, during the last five years there has been no better example of a syndemic than the case of Venezuela, "because public health problems have meant a major failure due to social practices in this country," added Rodríguez.

Without an immunisation strategy and budget to acquire enough vaccines, vaccine-preventable diseases like measles, polio, or diphtheria pose a major threat.

"In Colombia more than 95 percent of Malaria cases come from Venezuela, ”said Rodríguez. Colombia has also seen cases of COVID-19 imported from Venezuela.

Immunisation challenges after the pandemic

Pablo Kuri explained that a challenge for government authorities is to guarantee the supply of vaccines: there are not enough supplies or several vaccines currently.

In addition, he pointed out that this lack of vaccines is due to that there may be only one producer in the world, or it is not a profitable business and they stopped the production of some vaccines. "For example, for tuberculosis there is no profitable business, so they stopped producing it (vaccine)," said Kuri.

Another important challenge is finances, since you must have the resources to acquire the vaccines and immunise the population. However, sometimes it is not possible to do it universally, so there are strategies in place for the most vulnerable to be immunised.

Kuri pointed out that this is a strategy that is applied in Mexico with the flu vaccine, since it is not vaccinated universally, free of charge to the population that may be at risk, such as children, the elderly or the pregnant women.

No authority in the world should forget about the health agenda. In addition, it is necessary to ensure that there are sufficient funds and multilateral policies created to guarantee the strength of organisations that help control health crises, such as WHO and PAHO.

Leader Healthcare Group is a trusted provider of medical solutions to the healthcare market for over a decade. Headquartered in Dubai, their presence is well-rooted in the MENA, South East Asia, and APAC regions. The company has consistently taken the initiative to introduce innovation and technology to the healthcare industry. This progressive thinking motivated them to inspire the next generation of leaders. 

In January, Leader Healthcare hosted an appreciation ceremony for the students of Ajman University who participated in the “Leader Healthcare Volunteer Program”. The programme was held during Arab Health 2020 at Dubai World Trade Center. The objective of the programme was to offer a series of interactive learning experiences, structured working experience, mentoring and networking at events.

Essential training

The Leader Healthcare Volunteer program was considered a part of the student's external training as it is a mandatory requirement from the university as a part of their senior year. This is to give the students an introduction into the healthcare industry before they receive their bachelor's degree and step into the world of business and science.

This Ceremony included around 60 students and some of the Ajman University's senior faculty members, who attended the ceremony virtually observing COVID-19 restrictions. The ceremony was also a part of the students “Virtual External Training”.

Sukhdeep Sachdev, Global CEO of Leader Healthcare commenced the ceremony by welcoming the volunteers and the students who attended the ceremony virtually.

Sukhdeep's speech consisted of inspiring anecdotes, where he shared some of his experiences at the start of his career. He educated the students about "What it takes to be an entrepreneur". The discussion addressed hardships that successful entrepreneurs regularly face, and the important role perseverance plays in their journey.

He concluded the speech by promoting the volunteers to tackle future projects in science or business with commitment and determination.   

Suha Alkathiri (Volunteer Ajman University) stated: "It was a great experience for me. Leader Healthcare made me feel part of the team. A special thank you to Sukhdeep Sachdev for this opportunity as this experience added a lot to my educational journey."

Clinical laboratory workers believe that the work they perform in providing laboratory tests is valuable. However, data to validate this has been limited, and evidence of the contribution of laboratory medicine to the overall process of diagnosis and management is not easy to obtain. Many articles and presentations seeking to promote the value of laboratory medicine have made use of what has become known as the “70 per cent claim”. This is presented in various forms, most commonly that “Laboratory Medicine influences 70 per cent of clinical decisions”, or minor variations around this figure. However, the data on which this estimate was based represents unpublished studies and anecdotal observations and cannot now be objectively verified. In addition, much of the evidence relating to the value of laboratory medicine is poorly structured and does not relate to clinical outcomes.

We need more specific and evidence-based measures of the added value of laboratory medicine, which in turn require better-designed studies and better use of existing biomarkers. The mindset within laboratories in the past has too often been that our starting point is a specimen (of blood, other body fluid, tissue or whatever) and our endpoint is an accurate result. This tends to lead to a ‘factory’ mentality for laboratory workers, such that all their attention is focussed on improving processes within the laboratory. Undoubtedly, this is important – but we need to remember that the true starting point is a patient, and the true endpoint is an improved clinical outcome for that patient (Figure 1). The laboratory can add value to the testing process at every point along the pathway, by advising on appropriate requesting and proper sample collection, ensuring efficient and high-quality analysis and then converting results into useful information, which can inform decisions about diagnosis and treatment.

Figure 1

 

Improved clinical outcomes

The definition of value in healthcare is normally taken as the ratio of outcome to cost. Thus, better value is obtained when improved clinical outcomes are obtained at a lower cost, or greatly improved outcomes are obtained with relatively lower increases in cost. We know that laboratory medicine is particularly well leveraged in that respect, and laboratory testing has been called the most cost-effective intervention in medicine.

Assessing the value of laboratory medicine, therefore, requires a close focus on the impact of testing protocols on outcomes, which in turn requires a standardised set of measures of clinical outcome in all relevant clinical conditions – a “common currency” for outcomes, which enables clinical laboratory researchers to communicate the effect of using new biomarkers in terms of outcomes that are familiar to clinicians. Such standardised outcome measures have been absent in the past, but the work of the International Consortium for Health Outcomes Measurement (ICHOM) in bringing together international teams of patients, physicians and researchers to define outcomes that matter most to patients who live with different conditions is transforming this field and will allow much better analysis of the true clinical value of new biomarkers in specific situations.

A report by the Lewin Group in 2009 on the value of laboratory screening and diagnostic tests for prevention and healthcare improvement concluded that: “in order to improve outcomes, a laboratory test must be appropriately ordered, conducted, returned with results on a timely basis and affect a decision for further diagnosis and treatment”.

The work of Plebani’s group has clearly shown that where diagnostic error arises from laboratory testing, the pre- and post-analytical phases are much more vulnerable to error than the actual analytical phase, which implies that laboratories need to refocus their efforts on error reduction toward the total testing process rather than simply on the analytical aspects of their work.

Figure 2 shows an analysis of laboratory-related causes of diagnostic error. The first two causes – ordering of inappropriate tests and not ordering appropriate tests – are conveniently discussed together as better laboratory utilisation. This means working with clinicians to produce evidence-based guidelines on testing strategies, reducing inappropriate testing, which can lead to overdiagnosis and misdiagnosis, but – crucially – also ensuring that the right tests are done at the right point in the patient pathway, to ensure that the correct diagnosis is reached at the earliest possible point. As tests become more complex (particularly in the area of molecular genetics), specialist advice from the laboratory is vital to ensure that test selection is appropriate.

The third area listed in Figure 2, which can contribute to diagnostic error is a failure to use an appropriate test result properly, due to lack of understanding of the significance of the result or failure to integrate the test result into the overall clinical picture and the results of other investigations. The U.S. Institute of Medicine, in their 2015 report “Improving Diagnosis in Health Care” recommended that health care organisations should ensure that healthcare professionals should have the appropriate knowledge, skills, resources and support to engage in the diagnostic process, and laboratory workers have a crucial role in providing education in the proper use of laboratory testing and interpretation of results in specific cases.

Figure 2

 

Outcome-based evaluations

However good a laboratory test, it cannot affect the individual patient outcome if the result does not reach the clinician who is responsible for delivering care when it is needed (Figure 2, number 4). Test result management has been named as the #1 patient safety concern for 2019 by the U.S. ECRI Institute and urgent physician notification of critical results, both quantitative and qualitative, has become part of the standard of care because of the high impact it has on patient welfare and clinical outcomes. This means that laboratories must work with their users to decide, which results need to be communicated urgently, and by what means. It also means the development of effective electronic systems to indicate that a particular result has been seen and actioned by the relevant clinician, and (in some cases) follow-up by the laboratory of critical results, which have not been viewed or actioned.

The final point of Figure 2 – an appropriate test result which is wrong or inaccurate – is the traditional focus of laboratory quality management procedures. Constant vigilance in this area is essential, but (as mentioned above) it currently represents the least common cause of the diagnostic error.

In addition to efforts to improve how existing tests are used, it is vitally important that new biomarkers receive robust outcome-based evaluations before they are introduced into clinical practice so that the intended benefits of the biomarker are clearly understood, including the role of the new test, how and where it fits into the testing pathway (screening/triage/confirmation) and the clinical performance requirements for the test. The Test Evaluation Working Group of the European Federation of Clinical Chemistry and Laboratory Medicine have produced excellent work in this area including checklists for test evaluation

Laboratory doctors and scientists of the future must be involved in producing guidelines for investigation, advising clinical staff on the best strategy for individual clinical presentations and the further tests needed to confirm a diagnosis, and ensuring that results are not misinterpreted or missed and that resources (human, technical and financial) are used to do the right test on the right person at the right time. It’s a daunting challenge, but getting this right means better use of tests, better patient care, lower healthcare costs, improved job satisfaction for laboratory workers and enhanced ability to recruit and retain good scientists in laboratory medicine. That’s a goal worth working for! 

References available on request.

Vaccine-preventable diseases continue to take their toll worldwide despite the availability of safe and inexpensive vaccines. Outbreaks of infections with measles virus, in particular, are increasing in frequency in many parts of the world and have led to many deaths, especially in small children. Serological tests are an indispensable tool to support the diagnosis of acute infections and to establish past infections or the immune status in individuals. Other vaccine-preventable diseases for which serological diagnostics play an important role include mumps, rubella, varicella, pertussis, tetanus and diphtheria.

Measles

The measles virus belongs to the genus Morbillivirus within the family Paramyxoviridae. The virus causes an acute febrile illness, which occurs mainly in childhood and is very contagious. Nowadays, the disease generally occurs less frequently than in previous generations due to vaccination. In recent years, however, outbreaks of measles have been increasingly observed worldwide (Figure 1), in part due to stagnating vaccination rates. For example, in the European Region, the infection rate increased more than three-fold between 2017 and 2018 from 25,869 to 83,540 cases, according to the World Health Organisation. Measles represents one of the most common causes of death in infants worldwide. In the WHO European Region, 74 deaths from measles were recorded in 2018.

Figure 1: Occurrence of measles worldwide

Persons with acute infections exhibit a wide range of clinical symptoms. Characteristic is a mild self-limiting infection. Severe cases can, however, be fatal or cause severe disability. The incubation period for measles is typically about 10 days. The illness manifests with flu-like symptoms, encompassing fever, malaise, catarrh of the upper respiratory tract, cough, congestion and conjunctivitis. Soon afterwards the measles rash, a typical exanthema, appears first near the ears, then on the forehead, face and over the rest of the body.

Complications from measles include secondary bacterial pneumonia, otitis media, encephalitis, myocarditis, miscarriage and subacute sclerosing panencephalitis (SSPE). The latter is a progressive, generally fatal brain disorder caused by chronic measles virus infection. It occurs about 7 to 10 years after the infection and generally kills within three years from the onset of symptoms. Patients suffer from behavioural changes, cognitive deterioration, visual problems, and advanced neurological symptoms, which lead to severe physical and mental impairment and eventually death.

Vaccination

Due to the complications arising from measles virus infections, vaccination of infants is recommended by public health authorities. For example, the Robert-Koch Institute in Germany recommends two immunisation shots at ages 11 to 14 months and 15 to 23 months. The measles vaccine is often given together with mumps and rubella vaccines. Immunity is generally lifelong but can wane in individuals over 60. Moreover, antibody levels in post-vaccine sera are eight to 10 times lower than in convalescent sera. Consequently, a booster immunisation is recommended in persons over 60 to prevent severe life-threatening disease.

Serology

Serological testing is used to confirm the clinical diagnosis, alongside other methods such as direct detection of the virus. In primary infections, antibodies of class IgM develop soon after the onset of symptoms. According to the MiQ Immunological Methods for the Detection of Infectious Diseases (INSTAND e.V.), 70 per cent of patients exhibit IgM antibodies within three days of the appearance of the rash. The detection of IgM antibodies is considered an indicator of an acute infection. IgG antibodies are produced slightly later, soaring within two to four weeks. A significant increase in the IgG titer in two successive samples demonstrates an acute infection. A fresh infection can also be confirmed by means of an IgG avidity test. The presence of high-avidity IgG antibodies indicates an infection or vaccination that has occurred in the recent past. Breakthrough infections following earlier vaccination are characterised by moderate- to high-avidity antibodies and high neutralising antibody titers shortly after reinfection. IgM may be negative in these cases.

IgG antibodies are also suitable for determining the immune status since they remain detectable throughout the lifetime of the individual. It should be noted, however, that no difference can be serologically made between wild virus infection and vaccination. Therefore, knowledge of a patient’s medical history regarding illness and vaccination is paramount. New research has also shown that the immune protection from measles virus involves a complex interaction between cellular and soluble components of the immune system. Care should, therefore, be taken in the interpretation of results, as the immune response varies greatly between individuals. In general, an IgG concentration of over 200 mIU/ml is considered to be sufficiently protective according to the Robert Koch Institute.

Measles myelitis or encephalitis can be verified by analysing IgG antibodies against the virus in the cerebrospinal fluid (CSF). The involvement of the central nervous system in the disease is established by calculating the quotient of specific antibodies in CSF and serum compared to the quotient of total antibodies in CSF and serum, also known as the antibody specificity index.

Antibody detection methods

Specific antibodies against the measles virus can be measured in patient samples by immunological methods such as ELISA or chemiluminescence immunoassay. In ELISA, the use of viral lysate as the detection substrate enables highly sensitive detection of IgM antibodies in early infections. In the EUROIMMUN Anti-Measles Virus ELISA (IgM), for example, an inactivated lysate of cells infected with the measles virus strain Edmonston is used for the antibody detection. Viral lysates may, however, also occasionally induce unspecific reactions. A higher specificity can be achieved by using recombinant protein from measles virus for the antibody detection. The Anti-Measles Virus NP ELISA (IgM) is based on a recombinant nucleoprotein from measles virus, which provides more specific detection compared to lysate-based systems (Table 1).

Lysate-based ELISAs are preferable for determination of IgG antibodies. The EUROIMMUN Anti-Measles Virus ELISA (IgG) provides reliable measurement of IgG antibodies in serum or plasma and is suitable for both diagnostics and immune status determination. The ELISA is calibrated against the 3rd International Standard serum NIBSC 97/648. An IgG avidity test is also available for determination of the antibody avidity. The lysate-based ELISA for CSF diagnostics enables reliable detection of intrathecal antibody synthesis.

The performance of the ELISAs has been verified in various studies. In quality assessment schemes with pre-characterised samples, the Anti-Measles Virus NP ELISA (IgM) and the Anti-Measles Virus ELISA (IgG) achieved 100 per cent agreement with the target results. The lysate-based Anti-Measles Virus ELISA (IgM) yielded 99 per cent agreement, excluding one borderline result.

Further vaccine-preventable diseases

Serological analyses are also important in diagnostics and immunity surveillance of numerous other vaccine-preventable diseases. For example, detection of specific antibodies against rubella virus or varicella-zoster virus (VZV) supports the diagnosis of the respective infections and determination of the immune status. For detection of IgM antibodies against these viruses in acute diagnostics, purified viral glycoproteins are preferably used as the ELISA substrate in order to minimise unspecific reactions. Existing immunity to rubella virus or VZV can be established by measuring IgG antibodies using viral lysate-based ELISAs calibrated according to international reference sera.

Acute infections with mumps virus can be confirmed by determining specific IgM antibodies using ELISA based on viral lysate from either the wild type strain Enders or the currently circulating G5 strain. Immunity to mumps virus following vaccination cannot be conclusively verified serologically due to the lack of an international reference serum. However, seroconversion can be demonstrated by determining IgG antibodies against mumps virus. A special ELISA combining native antigens from the wild type strain Enders and the vaccination strain Jeryl Lynn provides an increased serological detection rate following vaccination, especially in children.

Serology also supports diagnostics of infections with Bordetella pertussis, the causative agent of whooping cough. Different reference laboratories recommend using only immunoassays which are based on species-specific pertussis toxin (PT) and which enable quantification in international units (IU/ml). The EUROIMMUN Anti-Bordetella PT ELISA detects specific antibodies against B. pertussis following infection or vaccination and enables exclusion of a B. parapertussis infection. Detection of IgG anti-PT antibodies at concentrations greater than 100 IU/ml indicates with high certainty a recent B. pertussis infection or vaccination. However, differentiation between infection and vaccination is not possible serologically. Moreover, the measurable antibody concentrations do not allow for any conclusions to be drawn regarding existing protection or immunity after vaccination.

For tetanus and diphtheria, ELISAs based on the toxoids from the corresponding bacteria, Clostridium tetani or Corynebacterium diphtheriae respectively, enable determination of the immune status and vaccination controls. The ELISA results are evaluated according to international reference preparations.

Perspectives

Health authorities worldwide are striving to eliminate a range of infectious diseases through comprehensive vaccination programmes. Nevertheless, outbreaks of vaccine-preventable diseases continue to occur worldwide. For highly contagious diseases such as measles, reliable identification and confirmation of cases are critical for early recognition of outbreaks, analysis of ongoing transmission, and estimation of the incidence. This enables among other things the development of vaccination strategies suited to local situations. Assessment of the immune status of individuals after vaccination or previous infection is important for identifying those with no or insufficient cover. These persons can consequently be offered additional vaccine shots to boost their immunity. This is beneficial both to protect the individuals and to bolster the herd immunity of communities.

This article was originally published on Conexión Expo Med.

Six months after the emergence of the SARS-CoV-2 coronavirus (COVID-19) in Wuhan, the disease has claimed thousands of lives. In Latin America more than 20 countries have reduced their activities and social interaction as a measure to curb infections, while health systems have faced one of their greatest challenges in case detection and patient care.

Related: Vaccination remains a priority in COVID-19 times

Little by little, the world is having to adapt to a “new normal”, with three processes expected to play a lead role: disinfection, sanitation and sterilisation.

These were precisely the topics addressed during Omnia Health Live, held on 22-26 by Informa Markets, that brought together professionals from the global healthcare industry.

Related: Latin American health systems need reconfiguring post-pandemic

During the session moderated by Marcelo Boeger, Vice President of AMTSBE (World Health and Wellness Tourism Association), speakers discussed how to prevent COVID-19 infections in the post-pandemic era.

In hospital systems and environments where group activities are carried out – corporate headquarters, offices, factories, restaurants, gyms, schools and recreational facilities, among other places –practices and cleaning methods must be integrated to eradicate bacteria and viruses.

In this regard, Brian Reynolds, President, IAHCSMM, asserted that in the “new normal”, it’s essential to take steps not taken regularly in the past, and although the adaptation process can be complicated, health personnel and all concerned must get used to it.

Patty Olinger, Executive Director of GBAC, ISSA division, explained that doctors and other health service providers must implement best practices to care for patients, supported by technology for sanitising instruments, equipment and facilities.

“The situation is changing very quickly, and we have realised that we must be more careful. We must work together to avoid being exposed to contagions and we also have to find ways to restore people’s confidence in revisiting crowded places that need to resume operations, through a quality management programme based on cleaning, disinfection and sanitation in all of North America,” said Olinger.

Similarly, she explained that these protocols cover simple actions such as frequent hand washing, cleaning of facilities and furniture, and the application of antibacterial gel, to compliance strategies for organisations.

Regarding measures to shield hospitals, the president of the IFHE said that technology is an ally, since telemedicine has facilitated the care of patients through virtual appointments or the sending or prescriptions by email.

“These are emerging processes and many things will need to be transformed, but they serve as a basis for us to be prepared in the future, in case we need to face another pandemic,” the manager said.

In this regard, Jason Unger, director of the Surgical Services and Anaesthesia Institute of the Cleveland Clinic, asserted that medical personnel have to be more proactive than reactive when providing effective care to patients remotely, in addition to reviewing patient flows in clinics and hospitals to avoid the interaction of healthy and sick people, where the use of masks, face masks and gloves will also be essential.

“We have to pay attention to details that seem simple but that have become necessary to guarantee that we and patients will be protected. We must change the view that it will take us longer to do so because understanding preventative measures correctly means that this extra time is a key factor in not contaminating us. We all need to change our perspective,” concluded Unger.