Medical Chronicle April 2021

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The doctor's newspaper

APRIL 2021

Ethics and legalities of mandatory vaccination

With the rollout of Covid-19 vaccines in SA, employers are facing the question of whether or not they can compel employees to undergo mandatory vaccination, and equally controversial, whether they ought to for the sake of fulfilling their health and safety obligations?

By Nicky Belseck, medical journalist

"T

HERE ARE A significant number of people around the world and indeed in SA that have indicated that they do not intend to be vaccinated against Covid-19, and the reasons for the objections are varied, some you may consider more rational than others, but be that as it may, they do exist,” said Verushka Reddy (director, Norton Rose Fulbright) during a webinar looking at the ethics and legalities of vaccines and vaccination.

“The SA government has made it clear that vaccination is voluntary, and it will be free.

Employers on the other hand are not necessarily

required to follow suit. So the question is, can employers compel their employees to undergo vaccination for Covid-19?

WHAT THE LAW SAYS “The two key pieces of legislation in the employment space are the Employment Equity Act and the Labour Relations Act,” said Reddy. “The Employment Equity Act prohibits direct and indirect discrimination against an employee as well as job applicants on grounds such as religion, conscience, belief, political opinion, or culture. The Labour Relations Act similarly prohibits dismissals on those grounds as well as prejudice to an employee on those grounds. So an employee’s decision not to vaccinate would likely fall into one of those listed grounds, most likely

conscience, and belief. Therefore, if an employee were to face adverse consequences based on their decision not to vaccinate in the workplace, an employer in general would find themselves falling foul of both the Labour Relations Act and the Employment Equity Act. If this is the case, a court may reverse the employers decision and an employee may be reinstated if they were dismissed or they may be compensated up to 24 months remuneration, and possibly also an employer may be required to pay damages that the employee is able to prove.

WHAT THE CONSTITUTION SAYS “Our Constitution guarantees everyone the right to human dignity,” said Laura Macfarlane (director, Norton Rose Fulbright).

“We also have the right to bodily and psychological integrity, which includes security and control over our own bodies and the right not to be subject to medical or scientific experiments without our informed consent. The Constitution further guarantees the right to privacy, and lastly, it enshrines the right to freedom of conscious religion, thought, belief and opinion. “When assessing whether a mandatory vaccination policy, or the consequences that may result from an employee refusing to comply, offends these rights we need to look at the context of each right, whether infringement would in fact occur, and if it doesn’t occur, whether it would be reasonable and justifiable, considering a number of factors including competing rights and interests in our country. continued on page 2

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NEWS

APRIL 2021

CONTENTS

All content in Medical Chronicle is sourced independently and under no circumstances should articles be considered promotional unless specified.

NEWS Ethics and legalities of mandatory

continued from page 1

“In our view, assessing all these rights, almost all of the rights would be implicated and infringed, and it would not be reasonable and justifiable in most instances to adopt a mandatory vaccination policy,” said Macfarlane.

constitutionally be seen as an operational requirement and whether such employee could not be accommodated. In general, the courts would require an employer not to take such a drastic step as dismissal, but to try to accommodate an employee.

IS THE HEALTHCARE INDUSTRY AN EXCEPTION TO THE RULE? “There are limited industries where an employer may be able to justify an employee’s dismissal based on their refusal to be vaccinate,” said Reddy.

“That would be on the basis of incapacity to perform their job. So employees working with vulnerable members of the public that may not have been vaccinated themselves, could potentially be required to be vaccinated by their employers.

Industries where this could apply may include old age homes and the healthcare industry. However, whether this would be permissible would largely depend on whether vaccination could reasonably and

THE ETHICAL QUESTION “Covid-19 will only stop being a threat if enough people are willing and are given the opportunity to vaccinate,” said Wits Bioethics & Health Law senior lecturer Dr Jillian Gardner. “Whether some of these mandatory, more coercive policies can be used within certain sectors, I think there certainly are arguments to be made for that, particularly in regard to the healthcare profession and the healthcare industry more broadly – nursing homes, people working in frail care homes, psychiatric facilities, and other spaces where people are institutionalised and there’s the likelihood of crowds, so prisons for example. One could see how those

could become possibilities, where some element of coercion may be justified where it’s not perhaps in other kinds of industries.

“The real ethical question is not if we should aim for herd immunity by implementing vaccine policies of some sort, but rather how and within what limits,” said Dr Gardner.

“These vaccination decisions and policies obviously present tension between individual rights and the moral duty to contribute to harm prevention. It comes down to whether you attach more weight to individual rights or to group benefits, or harm prevention to the community.

“Ultimately it comes down to recognising that herd immunity is an important tool to end this pandemic and it raises a whole set of questions in terms of people’s rights, questions around fairness, and how to balance these competing interests and values at stake.”

Covid: Vaccination – different strategies towards the ageing and we were warned!

Welcome to Medical Chronicle’s April issue. I hope the first quarter of the year has been kind to you and your loved ones.

W

E START OFF by looking at the hot topic of the ethics and legalities of mandatory vaccination. Legal firm Norton Rose Fulbrigh weighs in on the issues surrounding the laws on this, how it affects employers in general and healthcare workers specifically.

In a recent webinar hosted by the Oxford Institute of Population Ageing, Prof Refilwe Nancy Phaswana-Mafuya (UJ Epidemiology and Public Health, Faculty of Health Sciences) looked at SA and the importance of understanding epidemiologic heterogeneity of Covid-19 in the ageing population in order to guide a response. She highlights the importance of having different strategies towards the ageing population when it comes to Covid-19.

Fourteen years ago the World Health Organization cautioned governments of an imminent pandemic.

Following several influenza epidemics between 1995 and 2007 there were so many signals and warnings that the next

2 April 2021 | MEDICAL CHRONICLE

pandemic was around the corner. Should we have been more prepared? Prof Jeffrey Mphahlele, vice-president of the South African Medical Research Council shares his views on this topic.

Our CPD article (valid for 3 CEUS) explores non-surgical management of actinic keratoses and non-melanoma skin cancers. Actinic keratoses, basal cell carcinoma (BCC), squamous cell carcinoma and malignant melanoma are all pre-malignant and malignant skin cancers caused by photodamage. There are other rare tumours included in this group, such as Merkel cell carcinoma. Basal cell carcinomas are worldwide the most common skin cancer and can in certain circumstances be difficult to treat. The guiding hand of Dr Sian Hartshorne takes us through this important condition.

Covid-19 takes its toll physically and emotionally on those that it infects, but can it cause depression? Dr Marshinee Naidoo examines new research that suggests the virus may significantly increase chances of developing a psychiatric disorder.

We bring you two topical ethics articles. Don’t miss: Court upholds the importance of disclosure of medical records and The implications of prescribing and administering ivermectin.

Our opinion writer, Prof Morgan Chetty, asks when does long Covid end?

Keep an eye out for the announcements in the magazine of the many upcoming webinars.

vaccination..........................................................1 Epidemiologic heterogeneity of Covid-19 in SA’s ageing population .....3 We should have been ready for the Covid-19 pandemic........................................6 Will lessons learnt from Covid’s first & second waves make a difference?......8

CLINICAL

WEBINAR ANNOUNCEMENTS

Atopic dermatitis and food allergy What does the research say? ................5 Effects of Covid on stress and IBS and the management thereof ..........................7 The discovery of a new comedolytic addressing the microcomedone............9 Medical Recordkeeping: A healthcare practitioner’s window of opportunity................................................13 Fundamentals of allergy diagnosis...23 Rupatadine efficacy trials: Fill the gap ......................................................25 The burden of colorectal cancer in the South African landscape...........29

ONLINE CPDs

Investigating first-line phenylephrine infusion in patients with septic shock.........................................10 How treating sinus symptoms early can prevent a cough.......................19

WINTER AILMENTS

Returning to sports or exercise after recovering from Covid................................11 A recap of LRTIs .........................................22 Multi-Matrix 5-ASA to induce remission in ulcerative colitis? ................................24

CPD

Non-surgical management of actinic keratoses and non-melanoma skin cancers....................................................14

GASTROENTEROLOGY

Managing pancreatic exocrine insufficiency ................................................20

WOMEN’S HEALTH

SA's latest innovation in emergency contraception.................................................21 Postpartum complications increased in women with PCOS.......................................28

PSYCHIATRY

Can Covid-19 cause depression? ......26

ETHICS

Court upholds the importance of disclosure of medical records ...........30 The implications of prescribing and administering ivermectin .......................31

WEBINAR REPORT

Raising the bar in rheumatoid arthritis care .................................................32 Covid-19 in rhinology and allergy ......33

OPINION

When does long Covid end? .................34

Happy reading and stay safe!

PLACEBO

SABS issues new standard for hand sanitisers ...........................................35

PDS 3 COINT P

NEWS

Epidemiologic heterogeneity of Covid-19 in SA’s ageing population

It’s important to have different strategies towards the ageing population when it comes to Covid-19, because a homogenous approach in the context of a country with a high disease burden like SA can result in unsuitable interventions.

By Nicky Belseck, medical journalist

S

TILL A GROWING pandemic, SARS-Cov-2 remains high on the world public health agenda. In a recent webinar hosted by the Oxford Institute of Population Ageing, Professor Refilwe Nancy Phaswana-Mafuya (UJ Epidemiology and Public Health, Faculty of Health Sciences) looked at SA and the importance of understanding epidemiologic heterogeneity of Covid-19 in the ageing population in order to guide an equitable response.

“I believe very strongly that one cannot use a blanket approach, or you’ll end up with ineffective interventions, and we cannot assume heterogeneity,” said Prof Phaswana-Mafuya. “It will make our prediction models inaccurate. This makes it important to explore epidemiologic heterogeneities in terms of infection, severity, and mortality so as to understand the differential impacts and ultimately to guide governments and various stakeholders ensuring that control measures and resource allocation is accordingly structured.”

It’s important to have different strategies towards the ageing population when it comes to Covid-19, because a homogenous approach in the context of a country with a high disease burden like SA can result in unsuitable interventions CONSTRAINTS “It’s very difficult to monitor trends and patterns, even of mortality, without a captive audience. We know the embedded weaknesses of doing so because obviously generalisability is a problem with respect to hospital-based surveillance systems,” Prof Phaswana-Mafuya said, pointing out that SA’s national surveillance system monitoring cases and deaths is very generalised.

WHAT WE KNOW “The epidemic is growing and there’s marked heterogeneities in a number of cases and a number of deaths. We know that the Northern Hemisphere compared to the Southern Hemisphere has much more cases and deaths.”

Looking at cumulative graphs from the National Institute for Communicable Diseases (NICD) update reports, Prof

Phaswana-Mafuya pointed out that women clearly and consistently have higher Covid-19 infection rates than men. “There are various factors that have contributed to this including the fact that most frontline workers are women. Also, the health seeking

behaviours of men and women differ,” she said referring to men’s reluctance to seek health services, and the likelihood that more women have come forward to be tested.

“Across age groups you’ll see that Covid-19 infections and mortalities increase

by age,” she said. Prof Phaswana-Mafuya further highlighted that when looking at the percentage of deceased Covid-19 patients with comorbidities, hypertension and diabetes were the highest. This is important in the context of the ageing

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NEWS continued from page 3

population because the elderly have far more noncommunicable diseases (NCDs) than any other age group. “This is because their immunity levels become weakened in the physiological processes and become compromised and thus, they become vulnerable to acquiring viral or bacterial infections more than any other age group.”

Reviewing May 2020 data from NICD’s DATCOV surveillance system, Prof Phaswana-Mafuya showed the population aged 70+ had a 13.7% higher mortality compared to those who were under the age of 70. “This has serious implications,” she

said. “I also looked at the percentage of diseased Covid-19 patients having different comorbidities by age group at death and here you’ll see that firstly NCDs increase with increasing age, and the percentage of diseased patients was highest among those with hypertension. Hypertension was highest in the 60-69, 50-59, and 70+ age categories respectively, and diabetes and obesity were also highest in higher age groups. We can clearly see that these comorbidities are a critical factor in terms of Covid-19 impacts, and the issue of differential impacts becomes quite critical

given the fact that these comorbidities are quite prevalent in older age groups.

“In multivariate analysis, older age, being male, being non-white, and admission in public sector were strongly associated with Covid-19 mortality. Income inequalities, poverty levels, and unemployment rates make black Africans more disproportionately affected by Covid-19.”

The fact that being male was associated with Covid-19 mortality, Prof PhaswanaMafuya again attributed to the normal health seeking behaviours of men, which might lead to them only seeking help at a

much later stage when already severely sick. “They may also have had an underlying health condition that may not have been detected because they would not have gone to a health facility in the past. But a lot more needs to be done to establish the reasons for this.”

THE ISSUE OF MULTIMORBIDITY “The whole notion of multimorbidity is a very common phenomenon and there are shared determinants of NCDs – so when you have one, you’re likely to have the other,” explained Prof Phaswana-Mafuya. “These patients have been more vulnerable to Covid-19 mortality.

“The whole issue of multimorbidity adds to the complexity because there’s variable severity, variable physiological processes, and there are complexities in terms of pinning each one down to establish what actually transpires because there are multiple interaction effects, multiple confounding effects. This makes it important to have differentiative strategies towards the ageing population when it comes to Covid-19 because a homogenise approach in the context of a country like SA with a high disease burden can result in interventions that are amiss.”

In multivariate analysis, older age, being male, being non-white, and admission in public sector were strongly associated with Covid-19 mortality.

Income inequalities, poverty levels, and unemployment rates make black Africans more disproportionately affected by Covid-19 BOTTOM LINE “I believe that SA is one of the countries that has got the highest proportion of the elderly population, and it puts more weight on us as a country, but the ageing population deserves to be prioritised,” said Prof Phaswana-Mafuya.

“There’s still a lot to look into, the biological, behavioural, and environmental determinants. We’re learning as we go when it comes to Covid-19. I think utilisation of historical data, like triangulation of various data sources, will take us a long way in terms of determining where to go from here. Heterogeneity of Covid-19 and trying to find evidence that can inform policy makers in a very focused manner is vital,” she said in closing.

4 April 2021 | MEDICAL CHRONICLE

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Dr Cornelia M (Corli) Lodder practices as a General Practitioner in George, Western Cape. She has a special interest in allergic diseases and is a member of the Allergy Society of SA. In 2003 she received a Diploma in Allergology at the SA College of Medicine and in 2005 opened one of the first dedicated allergy clinics in private practice in Alberton. She was involved in the writing of new guidelines for the treatment of Allergic Rhinitis as a member of the Allergic Rhinitis Working Group of SA which was published the SAMJ in 2006, 2015 and the latest in July 2020. In 2007 she was appointed as a part time researcher in the Department of Immunology at the University of Pretoria. The results of her research were presented at congresses both locally and internationally and resulted in four publications in International Journals. She was awarded a PhD in Nov 2011. The title of her PhD is: “Investigation of the neutrophil-directed anti-inflammatory properties of the cysteinyl leukotriene receptor antagonist, montelukast.” Currently practicing as a GP and running an Allergy clinic in the practice in George, Western Cape. She is actively involved in lecturing at CME events mainly for general practitioners and pharmacists.

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References: 1. Luger T, De Raeve L, Gelmetti C, Kakourou T, Katsarou A, Lambert J, et al. Recommendations for pimecrolimus 1 % cream in the treatment of mild-to-moderate atopic dermatitis: from medical needs to a new treatment algorithm. Eur J Dermatol 2013;23(6):758–766. 2. Jensen J-M, Pfeiffer S, Witt M, Bräutigam M, Neumann C, Weichenthal M, et al. Different effects of pimecrolimus and betamethasone on the skin barrier in patients with atopic dermatitis. J Allergy Clin Immunol 2009;123:1124–1133.

3. Wahn U, Bos J, Goodfield M, Caputo R, Papp K, Manjira A, et al. Efficacy and Safety of Pimecrolimus Cream in the Long Term Management of Atopic Dermatitis in Children. Pediatrics. 2002;110(1).

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Covid-19 pandemic

Fourteen years ago the World Health Organization (WHO) cautioned governments of an imminent pandemic. Following several influenza epidemics between 1995 and 2007 there were so many signals and warnings that the next pandemic was around the corner.

B

ELIEVING THE WORLD was on the brink of an influenza pandemic, in 2007 the WHO projected that all countries would be affected, that widespread illness would occur, medical supplies would be inadequate, large numbers of deaths would occur (WHO’s conservative estimate was 2-7.4 million deaths), economic and social disruption would be immense, and that every country needed to be prepared.

While it may not have been an influenza virus, now facing almost 2.9 million deaths worldwide and Covid-19’s unprecedented impact on the global economy, perhaps we should have taken the WHO’s warning of an imminent pandemic more seriously.

LESSONS FROM PAST INFLUENZA PANDEMICS Perhaps the most important lesson we should have taken away from past influenza pandemics was the unpredictability of the epidemics.

“There was no seasonality in the previous pandemics, even though influenza occurs quite frequently during the cooler months of the year,” said Professor Jeffrey Mphahlele, vice-president of the South African Medical Research Council (SAMRC).

“There were great variations in mortality, severity of illness, pattern of illness, and age distribution, which is exactly what we’ve seen with Covid-19.

There is always a rapid surge in the number of cases over a brief period of time, often measured in weeks. Again, the two waves of SARS-CoV-2 speak to this rapid surge in the number of patients.

Pandemics tend to occur in waves with a duration of six-eight weeks and it’s difficult to predict whether subsequent waves will be more or less severe.”

KEY MEDICAL ASPECTS OF INFLUENZA THAT SHOULD HAVE PREPARED US “Influenza is highly contagious and can cause acute infection of the upper

and lower respiratory tract,” said Prof Mphahlele. “It can cause repeated infections due to viral mutations, is easily transmitted, and the incubation period is relatively short, usually two-three days.

The short incubation period is what enables the virus to spread globally within a short space of time. Unlike SARS-CoV-2, influenza is a segmented virus with eight RNA segments. These segments allow the virus to undergo mutations very easily.”

Influenza occurs quite frequently during the cooler months of the year

SARS & MERS The WHO may have been wrong about which virus would cause the next pandemic back in 2007, but it wasn’t like SARS-CoV-2 was the first coronavirus outbreak the world faced. Severe acute respiratory syndrome (SARS), a viral respiratory disease caused by a SARSassociated coronavirus, was first identified at the end of February 2003 during an outbreak that emerged in China and spread to four other countries. And in 2021 Middle East Respiratory Syndrome (MERS) also caused by a coronavirus was reported in Saudi Arabia. Just three years later, in 2015, the largest known outbreak of MERS outside the Arabian Peninsula occurred in the Republic of Korea. These should have prepared us better for the Covid-19 pandemic.

We can only hope that the world’s leaders will now take the threat of global pandemics seriously, optimising development of new health interventions such as vaccines, therapeutics, and rapid diagnostic tools to ensure we’re better equipped to face the next pandemic. Because it’s not a matter of if, but when.

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IBS = Irritable Bowel Syndrome; GI = gastrointestinal References: 1. Kinsinger SW. Cognitive-behavioral therapy for patients with irritable bowel syndrome: current insights. Psychol Res Behav Manag. 2017;10:231-237. 2. Moloney RD, Johnson AC, O’Mahony SM, Dinan TG, Greenwood-Van Meerveld B, Cryan JF. Stress and the Microbiota–Gut–Brain Axis in Visceral Pain: Relevance to Irritable Bowel Syndrome. CNS Neurosci Ther. 2016;22(2):102-117.

3. IMS Data October 2020. 4. Thakur AK, Shakya A, Husain GM, Emerald M, Kumar V. Gut-Microbiota and Mental Health: Current and Future Perspectives. J Pharmacol Clin Toxicol. 2014;2(1):1016. 5. Data on file.

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MEDICAL CHRONICLE | April 2021 7

NEWS

Did we learn anything from

Covid’s first and second waves?

As SA braces for the third wave of Covid-19 infections, will lessons learnt from the first and second wave make any difference?

By Nicky Belseck, medical journalist

W

HILE PREDICTIONS IN February had the third wave of Covid-19 infections hitting SA in May/June,

by March researchers were warning the third wave could hit parts of SA as early as April.

Following the second wave, the National Science and Technology Forum (NSTF) held a discussion Forum on issues of preparedness for human and animal disease outbreaks. The keynote speaker was former National Department of Health acting deputy director-general, Dr Yogan Pillay.

Discussing the lessons learnt from SA’s response to the Covid-19 pandemic so far, Dr Pillay identified six key intervention areas: community screening, contact tracing, active and informed use of epidemiological data, community engagement and risk communication, SA’s risk adjusted strategy, and health system strengthening.

COMMUNITY SCREENING & CONTACT TRACING “It was fairly clear from the first wave that the Health Department working alone was not going to be able to mitigate transmission or to prevent avoidable mortality. So, it was a major lesson that unless you work intersectorially and across all the spheres of government (local and national) a health sector response alone was not going to be sufficient.” Dr Pillay also stressed the need for community mobilisation at the lowest level. “Adherence to non-pharmaceutical interventions was significantly higher in communities where there was significant community mobilisation and significant involvement by local government councils.”

8 April 2021 | MEDICAL CHRONICLE

ACTIVE AND INFORMED USE OF EPIDEMIOLOGICAL DATA “It’s well known that in some areas we have really good surveillance data, in other areas not. We have to extend the digital platform we have to strengthen the surveillance system. There is some duplication and lack of standardisation across provinces, and there’s inadequate communication in many areas, but I think the Covid response has shown that the public and the private sector have to work more closely together, as should the national and provincial district levels. The only way to get ahead of a pandemic, which grows very fast, is to have electronic data systems.”

While it might not be ready in time for the third wave, Dr Pillay said, “I think what’s currently being built in terms of the labbased systems as well as the surveillance systems, including the modelling system through the Covid-19 modelling consortium will stand us in good stead so that if and when we get the next pandemic, we will be better prepared from an EPI (Epidemic Preparedness Index) and surveillance point of view.”

COMMUNITY ENGAGEMENT AND RISK COMMUNICATION Dr Pillay believed that from the beginning of the pandemic all mechanisms of communication had been used. “Everything from social media to radio and TV, and in all South African languages.” However, while the president and minister of health were at the forefront, of communication, he admitted that: “We could have had significantly more support in communication

from other government departments, and I think going forward that could increase.”

SA’S RISK ADJUSTED STRATEGY “The five-level alert system evolved out of significant consultation across all sectors, including private sector. Notwithstanding the fact that it did cause a significant amount of social and economic pain, because of the lockdowns. So going forward we need to learn lessons from what works and what doesn’t work at each of the levels, and what can be done differently. There’s been suggestions that you need a significant amount more community buy in before you institute an alert level, which means we need to not only balance between what’s done and how it’s done, but also between saving lives and saving livelihoods. While that’s become fairly clear, it’s a difficult balance to achieve.”

HEALTH SYSTEM STRENGTHENING “The lesson from the health system strengthening, and the lesson from the vaccines, is that SA has to become more self-sufficient in the production of commodities. Whether they are ventilators,

whether it’s production of oxygen, whether it’s PPEs, whether it’s the selection of drugs, steroids included, or whether it is coffins, regrettably, we’ve got to be able to become more self-sufficient in the production of these commodities because when you have a pandemic everybody in the world is looking for these commodities.”

Going forward Dr Pillay stressed the need to invest in public sector workers of all types, provide quality care at an affordable cost, and reduce the cost of inputs like diagnostics, vaccines, and medicines. “It means changing the way that the health and social sectors provide services. It also means greater reliance on digital technology for surveillance, self-monitoring of vital signs, and real time data for planning and intervention.”

THE THIRD WAVE With vaccines still in short supply, the vaccination rollout far from what’s needed to achieve herd immunity anytime this year, and SA bracing for the third wave of Covid-19 infections, it’s anyone’s guess whether the lessons learnt from the first and second waves will make any difference?

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Prof Jean-Hilaire Saurat

Dermatologist, Dermatology Department, Hospital Santa Caterina. Global Medical Director Eau Thermale Avène.

Professor emeritus at Geneva University

Date: 4 May 2021 Time: 19h00 Topic: T he discovery of a new comedolytic addressing the microcomedone Presenters: Prof Jean-Hilaire Saurat, Dr Ariadna Ortiz Brugués CLICK TO REGISTER: http://bit.ly/MicrocomedoneWebinar Dr Ariadna Ortiz Brugués obtained a Bachelor of Medicine from the University of Seville and the Albert-Ludwigs University of Freiburg, studying in the latter her doctoral thesis and obtaining the qualification "Cum Laude". She has carried out several stays and research projects abroad in prestigious centers such as the Massachusetts hospital in Boston, Harvard University; the Occupational and Environmental Dermatology service, Malmö University Hospital, in Sweden; the Oncodermatology service of the University Cancer Institute of Toulouse - Oncopole; and the Friedrichshafen Dermatopathology, in Germany. Scientific publications in journals of high impact factor such as JAMA Dermatology, The Oncologist, Clinical and Experimental Dermatology, Journal of Dermatology, Journal of the European Society of Dermatology and Venerology, Journal der Deutschen Dermatologischen Gesellschaft. Speaker in several national and international conferences. Professor at the Master in Quality of Life and Medical-Aesthetic Care of the Oncology Patient and at Master's Degree in Aesthetic Medicine (University of Alcalá) and at the Master of Aesthetic and Anti-Aging Medicine (Complutense University). Member of the European Group of Adverse Skin Events to Oncological Drugs, the Spanish Group of Cutaneous Lymphomas, the International Trichoscopy Society and the ISAD -OPENED Task Force.

Prof Jean-Hilaire Saurat, MD, is professor emeritus at Geneva University where he chaired the department of Dermatology for 28 years. He had studied Dermatology at the Hôpital Saint-Louis, and Experimental Pathology at the Faculté Necker Enfants Malades, both in Paris. Prof Saurat has been President of the International League of Dermatological Societies (ILDS), President of the European Society for Dermatological Research (ESDR), and the European Academy of Dermatology and Venereology (EADV). Prof Saurat has been chief editor of Dermatology 1986-2015 , and has been section editor of the Journal of Investigative Dermatology 1987-1997. He is the leading editor for editions 1st through 6th of the French Textbook of Dermatology ElsevierMasson pub. Prof Saurat’ current research includes: sebaceous glands pathophysiology, skin aging/dermatoporosis, 2 dermatotoxicology, and retinoids. His past research interests have included inflammatory skin diseases, graft-versushost reaction, severe drug reactions, and pediatric dermatology. Prof Saurat currently has a selected private practice in Geneva. Prof Saurat citations report indicates his 1 019 publications were cited 19 245 times, with an h-index of 66.

Prof. Saurat is “Chevalier de la Légion d’Honneur” France.

MEDChronicle

1. Tolerance and efficacy study under dermatological control on 51 subjects, use of Cleanance Comedomed twice a day for 56 days. 2. C

MEDICAL CHRONICLE | April 2021 9

ONLINE CPD

Investigating first-line phenylephrine infusion in patients with septic shock

Previous findings suggest that a delayed administration of phenylephrine replacing norepinephrine in septic shock patients causes a more pronounced hepatosplanchnic vasoconstriction as compared with norepinephrine.

This is a summary of a CPD article available on www.medicalacademic.co.za

N

EVERTHELESS, A DIRECT comparison between the two study drugs has not yet been performed.

Morelli et al (2008) performed a headto-head comparison study to compare the effects of a first-line therapy with either phenylephrine or norepinephrine on systemic

and regional haemodynamics in patients with septic shock.Previous findings suggest that delayed administration of phenylephrine in septic shock patients causes a more pronounced hepatosplanchnic vasoconstriction as compared with norepinephrine. Current evidence is that

the efficacy of haemodynamic optimisation by fluids and vasopressor agents critically depends on the urgency of therapy. It is therefore possible that the negative effects of hepatosplanchnic perfusion noticed previously in response to phenylephrine administration might have been related to a

PHENYLEPHRINE PRODUCES PERIPHERAL VASOCONSTRICTION AND INCREASES ARTERIAL PRESSURE IN SEPTIC SHOCK PATIENTS1 When your patient is admitted into ICU with septic shock they may present with: • Intravascular volume depletion2 • Decreased peripheral resistance2 • Hypotension2 • Non-uniform distribution of regional blood flow2

Vasoactive agents are needed to restore systemic vascular tone and to ensure adequate tissue perfusion2 DOSAGE1 In adult patients with septic or other vasodilatory shock: 0.5 mcg/kg/min to 6 mcg/kg/min by intravenous continuous infusion, titrated to blood pressure goal. Doses above 6 mcg/kg/ min do not show significant incremental increase in blood pressure.

Reference: 1. Phenylephrine Hydrochloride Injection, Approved package insert, December 2018. 2. Jain G, Singh DK. Comparison of phenylephrine and norepinephrine in the management of dopamine-resistant septic shock. Indian J Crit Care Med 2010;14(1):29-34.

S1 Phenylephrine Hydrochloride Injection (Solution for Injection). Each pack contains 5 x 1 ml ampoules. Each 1 ml ampoule contains 10 mg of Phenylephrine Hydrochloride. Reg. No. H630 (Act 101 of 1965). S2 Botswana: B9301910. NS1 Namibia: 14/5.1/0569.

For full prescribing information refer to the package insert approved by the Medicines Regulatory Authority.

Date of Publication of this promotional material: March 2021. Promotional Review Number: SAF2182563.

Abbott Laboratories S.A. (Pty) Ltd. Co. Reg. No. 1940/014043/07, Abbott Place, 219 Golf Club Terrace, Constantia Kloof, 1709. Tel: (011) 858 2000.

delayed treatment.

This was a prospective, randomised, double-blind, controlled clinical trial.

Patients were randomly allocated to treatment with either norepinephrine or phenylephrine infusion (n = 16 each) for 12 hours, titrated to achieve a mean arterial pressure (MAP) between 65 and 75 mmHg. RESULTS Main endpoint: Hepatosplanchnic perfusion assessed by the modification of the plasma disappearance rate of indocyanine green (PDR) and blood clearance of indocyanine green related to body surface area (CBI) after phenylephrine administration as compared with the norepinephrine group.

No differences were found between groups in the mean time elapsed from ICU admission to the need for vasopressor support (39 ± 35 hours vs 37 ± 38 hours, P = 0.282). In this regard, vasopressor administration was initiated as soon as the inclusion criteria were met (with no time delay).

Study drug requirements and systemic haemodynamics: Significantly higher doses needed for phenylephrine (P < 0.001).

• MAP significantly higher in the norepinephrine group (P = 0.011).

• No significant differences between groups in any other variable of systemic haemodynamics.

The length of ICU stay and the ICU mortality rates were similar between groups.

In terms of primary endpoints, there were no significant overall differences between groups. What we know: phenylephrine increases systemic vascular resistance by selectively stimulating 1 adrenoceptors without a compensatory increase in myocardial contractility, and thus in cardiac output.

CONCLUSION This is the first prospective, randomised, controlled study comparing systemic and regional hemodynamic effects of phenylephrine and norepinephrine infusion in the early phase of septic shock. These results suggest that phenylephrine – when administered as a first-line vasopressor agent in septic shock – is effective in increasing the MAP without compromising gastrointestinal and hepatosplanchnic perfusion as compared with norepinephrine.

The present study suggests there are no differences in terms of cardiopulmonary performance, global oxygen transport, and regional haemodynamics when phenylephrine was administered instead of norepinephrine in the initial hemodynamic support of septic shock.

References available on request.

10 April 2021 | MEDICAL CHRONICLE

CLINICAL | WINTER AILMENTS

Returning to sports or exercise after recovering from Covid

Sports medicine physician from a top American hospital, Cleveland Clinic, shares recommended guidelines, discusses health threats and identifies red flags to look for when exercising.

evaluated by a physician prior to restarting any type of exercise. Dr Schaefer says these people may need to have additional tests, including ECGs, heart imaging or blood work before they are cleared to start a progression back into activity.

MYOCARDITIS IN ATHLETES AND ACTIVE PEOPLE Dr Schaefer points to the possibility of myocarditis, which is an inflammatory response of the heart due to a viral infection, such as Covid-19. It can cause swelling in

the heart muscle making rigorous activity more difficult and sometimes, even deadly.

“Myocarditis is more likely to be found in people who had a moderate or severe case of the virus, but it can happen to anyone who was infected,” says Dr Schaefer.

continued on page 12

PRAVAFEN®

OPTIMISES DIABETIC LIPID TARGETS¹

TIMELINES DETERMINED BY SEVERITY OF COVID When an athlete or active individual is sick with Covid-19, they should not engage in any physical activity. During this time, they should focus on rest, good hydration, proper nutrition and following the advice of their physician or healthcare provider.

After this, the timeline of return to exercise or sport will be determined by how mild, moderate or severe the case was.

If an active individual or athlete only has a mild illness or tests positive without experiencing any symptoms, he or she can consider returning to activity after a 10day isolation period. Once that window has passed, the athlete may consider a gradual return to physical activity, but must not have symptoms. If an active individual or athlete had a moderate or a severe illness, or had to be hospitalised, he or she should be

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S COVID-19 AFFECTS everyone differently and the long-term effects are hard to predict, returning to exercise once recovered should be undertaken with great care, especially in the case of moderate to severe cases of Covid-19, says an expert from a top American hospital, Cleveland Clinic. Sports medicine physician Dr Marie Schaefer says: “The truth is, the disease can affect everyone differently.

Anyone, including young athletes, could experience a severe case or have long-term damage, which is why it is so important to take this seriously.” While experts know that in some people the virus can lead to damage of the heart, brain, lungs and kidneys, she says there is no way to pinpoint or predict who exactly these individuals will be. Some might also experience lingering symptoms, including shortness of breath, muscle aches, loss of stamina and exhaustion.

For many athletes and active people, Dr Schaefer says, returning to activity will likely be a slow process and will require patience.

Individuals should work with a physician to make sure they are progressing appropriately and to monitor their symptoms.

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Why Pravafen

• SA’s first combination therapy to reduce the residual risk factors remaining in diabetic patients on statin therapy2,3 • Pravafen® is the only single treatment to address all risk-contributing aspects of the atherogenic triad2,4 • Pravafen® alters the atherogenic properties of LDL particles, thereby reducing residual risk2,3 • In diabetic patients the correct statin matters. Pravafen® contains a safe statin and fibrate combination with the only statin that has beneficial effects on the glucose metabolism5 • Reduces the risk of CVD events by 36 % in patients with Atherogenic Dyslipidaemia*6 *Statin/Fibrate combinations 1. American Diabetes Association Diabetes Care [Internet]. 2002; suppl 1:s74-s77. Available from: https://doi.org/10.2337/diacare.25.2007.S74. 2. Mach F, et al. ESC Scientific Document Group. 2019 ESC/EAS Guidelines for the management of dyslipidaemias:lipid modification to reduce cardiovascular risk: The Task Force for the management of dyslipidaemias of the European Society of Cardiology and European Atherosclerosis Society. European Heart Journal [Internet]. 2020; 41 (1): 111–188. Available from: https://doi.org/10.1093/eurheartj/ehz455. 3. Laufs U, et al. Clinical review on triglycerides. European Heart Journal [Internet]. 2020; 41(1):99-109c. Available from: https://pubmed.ncbi.nlm.nih.gov/31764986/ doi: 10.1093/eurheartj/ehz785.

4. Farnier M, et al. Fixed-Dose Combination Fenofibrate/ Pravastatin 160/40 mg Versus Simvastatin 20 mg Monotherapy in Adults With Type 2 Diabetes and Mixed Hyperlipidemia Uncontrolled With Simvastatin 20 mg: A Double-Blind, Randomized Comparative Study. Clinical Therapeutics. 2011;33(1):1-12. 5. Kostapanos MS, et al. Do Statins Beneficially or Adversely Affect Glucose Homeostasis? Current Vascular Pharmacology. 2010; 8(5):612-31. Available from https://doi. org/10.2174/157016110792006879. 6. Kim N, Kim S. Fibrates Revisited: Potential Role in Cardiovascular Risk Reduction. Diabetes & Metabolism Journal [Internet]. 2020; 44(2):213. 7. Farnier M,et al. Efficacy and Safety of Adding Fenofibrate 160 mg in High-Risk Patients With Mixed Hyperlipidemia Not Controlled by Pravastatin 40 mg monotherapy. The American Journal of Cardiology. 2010;106(6):787-792.

S4 Pravafen 40/160 mg hard capsules. Each hard capsule contains 40 mg pravastatin sodium (equivalent to 38,03 mg pravastatin) and 160 mg fenofibrate. Reg No: A 52/7.5/0769. Marketed by: Austell Pharmaceuticals (Pty) Ltd. 1 Sherborne Road, Parktown, Johannesburg, 2193.0860 AUSTEL / 0860 287835 www.austell.co.za PMX 1068_10/2020

MEDICAL CHRONICLE | April 2021 11

CLINICAL | WINTER AILMENTS

continued from page 11

Given this increased potential risk for myocarditis, athletes or active people returning after Covid-19 infections need

to be cleared by a healthcare provider who will determine if any additional testing is needed. Because of the risk of myocarditis,

athletes and anyone who exercises should follow a graduated return to physical activity over the course of a week

to monitor for signs and symptoms of this serious complication.

EASING BACK INTO FITNESS While serious athletes should follow a Return to Play (RTP) schedule supervised by a professional trainer or physician, Dr Schaefer has three pieces of advice for anyone planning to reintroduce exercise into their routine.

1. Listen to your body. If someone is experiencing symptoms like chest pain or heart palpitations, they should stop exercising immediately and consult with a doctor. Exercise and movement are important for overall health, but for Covid-19, things can change overnight as we learn more about the virus, she says. People should keep monitoring themselves and if something feels more serious than just a consequence of being out of shape, they need to stop exercising and talk to a physician.

If individuals experience any of the follow red flag symptoms, they stop exercising immediately: • Chest pain or heart palpitations • Nausea • Headache • High heart rate not proportional to exertion level or prolonged heart rate recovery.

• Feeling lightheaded or dizzy • Shortness of breath, difficulty catching breath or abnormal, rapid breathing • Excessive level of fatigue • Swelling in the extremities • Syncope (passing out) • Experiencing tunnel vision or loss of vision.

2. Take it easy. Recovered patients should not try to 'power through' as they did in the past. Athletes of all ages should follow a gradual progression to get back into exercise. They will need to build up the time and intensity of their workouts.

Dr Schaefer advises starting with a slow walk and if that feels alright, trying a brisk walk the next day. They will need to gradually increase the time they spend walking, building this up for about one to two weeks before returning to HIIT training or CrossFit, for example.

3. Be patient. Dr Schaefer points out that even if someone the recovered patients were training for a marathon prior to becoming infected, they will likely discover that their body has changed a bit, which warrants extra caution. “Do not push too hard on a body that is still trying to recover,” she concludes.

12 April 2021 | MEDICAL CHRONICLE

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operations, and to a top treatment and research centre overseas regarding the terms of use of artificial intelligence medical treatment plans in South Africa. More recently, Natasha advised on vaccine laws in Africa in relation to indemnification and vaccine injury compensation systems, class actions and product liability litigation in Africa. Natasha has performed risk assessments and advised on supplier agreements in relation to the procurement of the Covid-19 vaccine. She has written and published articles and presented at medical and insurance seminars and conferences.

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MEDICAL CHRONICLE | April 2021 13

CPD | DERMATOLOGY

Non-surgical management of

actinic keratoses and non-melanoma skin cancers Actinic keratoses, basal cell carcinoma (BCC), squamous cell carcinoma and malignant melanoma are all pre-malignant and malignant skin cancers caused by photodamage. There are other rare tumours included in this group, such as Merkel cell carcinoma. Basal cell carcinomas are worldwide the most common skin cancer and can in certain circumstances be difficult to treat.

To earn your CPD points answer the quiz on www.medicalacademic.co.za

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ON-SURGICAL TREATMENT of these premalignant and malignant skin cancers, especially for those in difficult areas and those with large tumour size, includes cryotherapy, topical imiquimod, topical 5 -fluorouracil and photodynamic therapy. This article will focus on AK and BCC. Actinic keratoses are small, scaly, sandpaper-like papules found on sunexposed areas of skin including the face, balding scalp, and arms. Histologically actinic keratoses are a proliferation of cytologic atypical keratinocytes in the epidermodermal junction zone. With a risk of evolving into squamous cell carcinoma these lesions are considered to be premalignant.

Ultraviolet light, specifically UVA and UVB directly and indirectly cause of specific mutational damage changes to the DNA

in keratinocytes. Long-term UV radiation is known to produce local and systemic immunosuppression, mutations in the p53 tumour suppressor gene, and DNA pyrimidine covalent dimers, all of which are believed to contribute to the development of AK. General risk factors for the development of AK are numerous and well-established.

RISK FACTORS One of the most prominent is the age of the patient, with patients older than 40 at increased risk and patients of an advanced age at a far greater risk than average. Having lighter skin and hair, especially red or blonde, indicates an increased risk, as does chronic sun-exposure.

The progression from AK to squamous cell carcinoma has an incidence of anywhere

’s No. SA A’s No

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SHEDDING SOME LIGHT ON TREATING AK*

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BY BY DERMATOLOGISTS§1§1 DERMATOLOGISTS

between 0.025%-16%, differing according to various research. In widespread AK this carcinogenic risk therefore increases exponentially. It is therefore good preventative clinical practice to treat actinic keratoses. However extensive widespread AK presents a challenge to treat.

Data has shown that the non-surgical treatment modalities most commonly used to treat AK are cryotherapy, topical imiquimod, topical 5-flourouracil and photodynamic therapy.

Dr Sian Hartshorne is a practicing dermatologist and current president of the South African Society for Dermatologic Surgery and the scientific programme co-ordinator of the African Women’s Dermatologic Society, who has the following findings on the topics of AK and BCCs.

Dr Sian Hartshorne

CLINICAL PRESENTATION OF ACTINIC KERATOSES: • Papules and plaques (1mm – 2.5cm) • Flesh-coloured, slightly red-brown pigmented • Erythematous • Rough, hyperkeratotic surface • Light-exposed areas (mainly face, lower lips, bald areas on the head, neck, arms, hands)

Worldwide, more dermatological experts prefer imiquimod2**

Category D6B topical chemotherapeutic agents * Actinic Keratosis; ** Evidence- and consensus-based (S3) Guidelines for the Treatment of Actinic Keratosis;

References: 1. Impact Rx - September 2020. 2. Werner RM. et al. Evidence- and consensus-based (S3) Guidelines for the Treatment of Actinic Keratosis - International League of Dermatological Societies in cooperation with the European Dermatology Forum - Short version. JEADV 2015;29:2069-2079.

Scheduling status: S4 Proprietary name and dosage form: ALDARA Cream. Composition: Each 2,0 g cream pump contains 5 % Imiquimod (100 mg). ALDARA Cream Sachet. Composition: Each 250 mg cream sachet contains 5 % Imiquimod (12,5 mg). Preservatives: Methyl hydroxybenzoate 0.2 % m/m, Propyl hydroxybenzoate 0.02 % m/m, Benzyl alcohol 2 % m/m. Pharmacological classification: A 34 Other. Indications: ALDARA Cream is indicated for the topical treatment of superficial basal cell carcinoma (sBCC), and of external genital/perianal warts (condyloma acuminata) and clinically typical, non hyperkeratotic, nonhypertrophic actinic keratosis (AKs) on the face or scalp in adult patients. Registration number: 32/34/0541. Name and business address of the holder of the certificate of registration: iNova Pharmaceuticals (Pty) Ltd. Co. Reg. No. 1952/001640/07, 15e Riley Road, Bedfordview. Tel. No. 011 087 0000. www.inovapharma.co.za. For full prescribing information, refer to the package insert as approved by the SAHPRA (South African Health Products Regulatory Authority). Further information is available on request from iNova Pharmaceuticals. 15200L. IN4059/21.

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May 2021 | MEDICAL CHRONICLE | EXPIRY DATE 30th MAY 2022

2021/02/23 09:28

CPD | DERMATOLOGY

Superficial basal cell carcinoma

• Often itchy • May cause thickening of skin in response to scratching therefore resulting in large hyperkeratotic nodules.

NATURAL COURSE OF AK There are three possibilities in the clinical course of AK – persistence, spontaneous regression and progression to invasive SCC (0.025% to 16%). However, we have no ability to predict what will be the outcome of any AK. Risk of progression to SCC increases with the increase in number of actinic keratoses.

The mortality rate of invasive SCC is approximately 1%. The risk of progression is minimised by effective treatment and all AKs should be treated. Prevention of widespread AK is through daily sunscreen use. This prevents development of new AK, SCC and has an additional moisturising benefit. With daily sunscreen use, there can be a decrease in the average number of existing AK of approximately 30% (if daily sunscreen is used over two year period).

MANAGEMENT OF WIDESPREAD AK Moisturisers decrease the dryness and scaling and therefore help to ‘flatten’ keratoses and decrease itch. The combination of moisturising sun protection plus other preparations may help to decrease actinic keratoses. The following preparations can be used to decrease the scaling of actinic keratoses: • 10-20% Salicylic acid in UEA • 10% Lactic acid in UEA • Use at daily on arms and legs • Stop if skin becomes too irritated • Chemical peels – up to 70% glycolic acid peels NONSURGICAL MANAGEMENT OF AK Physical therapies include cryotherapy, surgical excision, radiation and laser.

Topical therapies include imiquimod, 5-Fluorouracil, diclofenac, and ingenol mebutate. Photodynamic therapy is also an option.

CRYOTHERAPY Cryotherapy involves the application of liquid nitrogen for 20-40s, in a spray technique. Cotton wool wrapped onto a wooden orange stick or pus swab can be used for more focused areas, especially for facial areas.

The roll technique of cryotherapy is a lighter technique over large areas decreasing pain and blistering, and leading to quicker healing, less scarring and hypopigmentation.

IMIQUIMOD Imiquimod is a novel topically active positive immune response modifier that enhances the body’s immune response against dysplastic cells. It is a member of imidazoquinolines family. It has proven strong antiviral (HPV) and anti-tumour properties.

Imiquimod mode of action Imiquimod enhances non-specific and specific immune response, especially cellmediated pathways. It activates dendritic cells through Toll-like receptor 7. Activated dendritic cells migrate to local lymph nodes and initiate T-cell activity. It induces IFNa, IL6, IL12, TNFa. T-cells then travel via the bloodstream and selectively destroy dysplastic cells of the actinic keratoses.

It also induces immunologic memory.

Imiquimod induces cellular memory via the activation of effector T-cells, Langerhans cells, lymphocytes, and macrophages. These cells circulate lymphatically and activate the adaptive immune response. Imiquimod’s ability to induce immunologic memory results in a low incidence of recurrence.

Imiquimod should be applied three times per week at night. For example, Monday, Wednesday and Friday for four weeks.

Advantages of imiquimod It is highly selective and has a specific effect on dysplastic cells, with no effect on normal cells, and a treatment effect on subclinical actinic keratoses. Surface field treatment can be achieved (field cancerisation), for example on the scalp.

There is an excellent cosmetic outcome.

It is cost effective and easy to use in elderly or those on many medications.

In a comparative study (Krawtchenko, 2007) comparing imiquimod vs 5-FU and cryotherapy, imiquimod showed the highest sustained clearance rates at one year follow-up of both the lesions that were initially treated and of the treatment field.

Disadvantages of imiquimod Disadvantages include flu like symptoms if there is a very severe reaction: Myalgia, headache, fatigue. Local skin reactions such as redness, itching and burning can occur as with many of the topical treatments. There may be photosensitivity, so patients are advised to avoid sunlight as much as possible, wear sunblock and protective clothing. Use with caution in patients with autoimmune disorders or organ transplant/ immunosuppression.

5-FLOUROURACIL Similarly to Imiquimod 5-Fluorouracil can be used to treat extensive actinic keratoses.

However the mode of action is a more direct chemotherapeutic effect via interference of DNA synthesis and RNA transcription.

The cream is applied twice daily for 14-21 days and should elicit a very red reaction. Although very effective there are the disadvantages of burning and discomfort locally on the areas treated.

Once treatment is completed these symptoms clear rapidly and there should be an excellent cosmetic outcome.

PHOTODYNAMIC THERAPY Photodynamic therapy (PDT) is a treatment for AK, basal cell carcinoma and Bowen’s disease involving the topical application of a light-sensitive substance followed by its activation through illumination with a specific light source.

An incidental benefit is photorejuvenation. For photodynamic therapy of widespread AK, one must prepare the skin

well by removing as much hyperkeratosis as possible and cover all treatment areas for three hours.

For arms and legs with very thick hyperkeratotic plaques, prepare skin for two weeks prior to treatment with: 5-fluorouracil twice daily or 20% salicylic acid in UEA or cryotherapy or 70% glycolic acid peel. This produces an excellent recovery and cosmetic end result but it can be expensive.

COMBINATION THERAPIES OF TREATMENT OF WIDESPREAD ACTINIC KERATOSES These include: • Glycolic acid peels, cryotherapy and micropore wraps • Glycolic acid peels, cryotherapy and PDT • 5-Fluorouracil and PDT • Microneedling and PDT • Fractionated CO2 laser and PDT. BASAL CELL CARCINOMA Basal cell carcinoma (BCC) are slowly growing, locally invasive tumours of the skin that arise from basal layer of epidermis and from hair follicles. They form 80% of non-melanoma skin cancers and are the most common form of skin cancer in fair skin colour patients (Fitzpatrick I/II).

The incidence of BCC continues to rise by approximately 10% per year.

BCC is the most common skin cancer, especially in fair-skinned populations.

The incidence of BCC continues to rise by approximately 10% per year.

Although nodular BCC is the most common subtype of BCC, superficial BCC (sBCC) accounts for 10%-17% of all BCCs and up to 38% of BCCs in certain locations, such as the neck. Squamous cell carcinoma (SCC) is the second most common cutaneous neoplasm, with in situ carcinoma accounting for approximately 12%.

Collectively, sBCC and SCC in situ represent a substantial percentage of malignant cutaneous neoplasms.

BCC, the most frequently occurring cutaneous malignancies, generally do not MEDICAL CHRONICLE | April 2021 15

CPD | DERMATOLOGY

metastasize but can be locally invasive. The treatment aim is to completely cure the tumour, but the cosmetic outcome is also a reasonable concern for patients.

BCC occur in mostly sun-exposed areas as a result of UV light damage. It is known that in rare genetic disorder Gorlin-Goltz syndrome patients have multitudes of BCC and that there is an aberrant activation of hedgehog (HH)/glioma-associated oncogene signalling pathway.

BCC can be classified into different histological sub-types according to their growth pattern. The different histological

sub-types broadly distinguish between nodular, superficial and infiltrative, and other less frequently occurring types according to their growth patterns.

Micro-nodular and infiltrative sub-types are recognised as high risk and should rarely be treated other than surgically. Apart from the histological appearance, other well-recognised factors that can influence the prognosis and outcomes for treated BCC are the size and site of the tumour, how clearly the margins are defined and failure of previous treatment.

CAUSES AND RISK FACTORS Basal cell carcinomas occur in mostly sun-exposed areas as a result of UV light damage. Exposure to ultraviolet radiation is therefore generally accepted as the major cause of basal-cell carcinoma. Whereas SCC appears to be strongly related to cumulative sun exposure, the relationship between exposure to ultraviolet radiation and the risk of BCC is more complex.

The timing, pattern, and amount of exposure to ultraviolet radiation all appear to be important. The risk of this disease is significantly increased by recreational

CHANGING THE NATURE OF TREATMENT

Consider Aldara as a first choice for Actinic Keratosis (AK) and superficial Basal Cell Carcinoma (sBCC)

• • •

•

• •

Worldwide, more dermatologists prefer 5 % imiquimod to 5 % 5-FU for treatment of AK*1 Superior sustained clearance and cosmetic outcomes vs. 5-FU and cryotherapy2 Effective for multiple, multiform AKs3

5 % Imiquimod cream is superior to both MAL-PDT and 5 % 5-FU cream and considered a first choice by dermatologists for sBCC**4 Preferred by patients to surgery for treatment of low risk sBCC^5 Effective for multiple or large sBCCs6,7

5-FU: 5-fluorouracil; MAL-PDT: methyl aminolevulinate photodynamic therapy. *Evidence- and consensus-based (S3) Guidelines for the Treatment of Actinic Keratosis – International League of Dermatological Societies in cooperation with the European Dermatology Forum: imiquimod had a higher agreement (≥ 75 %) than 5-FU (≥ 50 %) as suggested treatment for single or multiple AK lesions.1 **A 5-year follow-up study of 601 patients with sBCC concluded that imiquimod is considered first choice for non-invasive treatment of most primary sBCCs because it was superior to both Photodynamic therapy and 5-FU in terms of efficacy of sBCC.1 ^Analysis of the SINS trial evaluating long term success of excisional surgery vs. imiquimod for low risk sBCC, showed that patients preferred ALDARA to surgery, regardless of previous experience of BCC symptoms and treatment2 References: 1. Werner RM. et al. Evidence- and consensus-based (S3) Guidelines for the Treatment of Actinic Keratosis – International League of Dermatological Societies in cooperation with the European Dermatology Forum – Short version. JEADV 2015;29:2069-2079. 2. Krawtchenko N. et al. A randomised study of topical 5% imiquimod vs. topical 5-fluorouracil vs. cryosurgery in immunocompetent patients with actinic keratoses: a comparison of clinical and histological outcomes including 1-year follow-up. Br J Dermatol 2007;157 (Suppl.2):34-40. 3. Stockfleth E. et al. Treatment of multiple, multiform actinic keratoses on the head with imiquimod 5% cream. Eur J Dermatol 2009;19(4):1-5. 4. Jansen M. et al: Five Year Results of a Randomized Controlled Trial Comparing Effectiveness of Photodynamic Therapy, Topical Imiquimod, and Topical 5-Fluorouracil in Patients with Superficial Basal Cell Carcinoma. J Invest Dermatol 2018;138:527-533. 5. Tinelli M. et al. What determines patient preferences for treating low risk basal cell carcinoma when comparing surgery vs imiquimod?

A discrete choice experiment survey from the SINS trial. BMC Dermatol 2012;12:19. 6. Shumack S. et al. 5% Imiquimod Cream for the Treatment of Large Superficial Basal Cell Carcinoma. Arch Dermatol 2004;140:1286-1287.

7. Marks R. et al. Efficacy and Safety of 5% Imiquimod Cream in Treating Patients With Multiple Superficial Basal Cell Carcinomas. Arch Dermatol 2004;140:1284-1285.

Scheduling status: S4 Proprietary name and dosage form: ALDARA Cream. Composition: Each 2,0 g cream pump contains 5 % Imiquimod (100 mg). ALDARA Cream Sachet. Composition: Each 250 mg cream sachet contains 5 % Imiquimod (12,5 mg). Preservatives: Methyl hydroxybenzoate 0.2 % m/m, Propyl hydroxybenzoate 0.02 % m/m, Benzyl alcohol 2 % m/m. Pharmacological classification: A 34 Other. Indications: ALDARA Cream is indicated for the topical treatment of superficial basal cell carcinoma (sBCC), and of external genital/perianal warts (condyloma acuminata) and clinically typical, non hyperkeratotic, nonhypertrophic actinic keratosis (AKs) on the face or scalp in adult patients. Registration number: 32/34/0541. Name and business address of the holder of the certificate of registration: iNova Pharmaceuticals (Pty) Ltd. Co. Reg. No. 1952/001640/07, 15e Riley Road, Bedfordview. Tel. No. 011 087 0000. www.inovapharma.co.za. For full prescribing information, refer to the package insert as approved by the SAHPRA (South African Health Products Regulatory Authority). Further information is available on request from iNova Pharmaceuticals. 16596L. IN3641/20.

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16 April 2021 | MEDICAL CHRONICLE

exposure to the sun during childhood and adolescence. Intense intermittent exposure to the sun is associated with a higher risk of BCC than is a similar degree of continuous exposure.

Physical factors, including fair complexion, red or blonde hair, and light eye colour, influence responsiveness to ultraviolet radiation but are also independent risk factors. Exposures to ionising radiation, arsenic and oral methoxsalen have also been linked to the development of BCC. It is also known that in rare genetic disorder Gorlin-Goltz syndrome (basal cell naevus syndrome) patients develop multitudes of BCC due to a mutation on the PTCH1 gene which results in an aberrant activation of the hedgehog (HH)/gliomaassociated oncogene signalling pathway.

Immunosuppression predisposes patients to BCC. The 4:1 ratio of BCC to SCC seen in immunocompetent patients is reversed in organ-transplant recipients. Among Australian heart-transplant recipients, there were 21 times as many cases of BCC as among Australians who had not received a heart transplant, and 123 times as many cases as among Americans who had not received a heart transplant. Renaltransplant recipients have a risk of BCC that is 10 times that among a population of those who have not received renal transplants.

In a meta-analysis of seven studies, Marcil and Stern showed that after an index case of BCC, the incidence of subsequent cases among such patients was increased by a factor of 10, as compared with that in the general population. Significant predictors of a greater number of BCC include an initial truncal occurrence, an age of more than 60 years at the first presentation, the presence of the superficial histologic subtype, and male sex.

Susceptibility to a truncal location has been linked with genetic polymorphisms in glutathione S-transferase and cytochrome P-450.

Risk factors for extensive subclinical spread include a tumour diameter greater than 2cm, location on the central part of the face or ears, long-standing duration, incomplete excision, an aggressive histologic pattern of growth, and perineural or perivascular involvement. Tumours with subclinical extension or indistinct borders are more frequently associated with residual positive margins after excision and have a higher recurrence rate than more limited or well-defined tumours.

Metastasis of BCC is extremely rare occurring in rare genetic disorders such as Gorlin -Goltz syndrome. Metastases arise most commonly from primary tumours on the face and ear, with the median interval between the appearance of the tumour and metastasis estimated to be nine years. The prognosis for metastatic disease is poor, with mean survival ranging from 8 months to 3.6 years.

CLINICAL PRESENTATION AND HISTOLOGIC APPEARANCE BCC characteristically arises in body areas

2021/02/23 09:23

CPD | DERMATOLOGY

Pigmented nodular basal call carcinoma

exposed to the sun and is most common on the head and neck (80%), followed by the trunk (15%) and arms and legs. BCCs have also been reported in unusual sites, including the axillae, breasts, perianal area, genitalia, palms, and soles.

Nodular BCC is the classic form, which most often presents as a pearly papule or nodule with overlying telangiectases and a rolled border, at times exhibiting central crusting or ulceration. Occasionally, nodular BCC may resemble enlarged pores or pits on the sebaceous skin of the central portion of the face. Superficial BCC presents as a slowly growing scaly erythematous pink patch or plaque, which resembles eczema, psoriasis, or Bowen’s disease (intraepidermal carcinoma).

Both nodular and superficial forms may contain melanin, imparting a brown, blue, or black colour to these lesions.

The morpheaform type, also known as sclerosing, fibrosing, or infiltrative BCC, typically appears as an indurated, whitish, scar-like plaque with indistinct margins.

Suspicious lesions occurring in highrisk areas, such as the central portion of the face, should undergo prompt biopsy to obtain a timely diagnosis and to expedite definitive treatment. Skin biopsy will also identify amelanotic (nonpigmented) or

minimally pigmented melanomas, which can sometimes mimic BCC. In a review of 1039 consecutive cases of BCC, Sexton et al found that the most common histologic subtypes are mixed (38%), nodular (21%), superficial (17%), and micronodular (14%). Uncommon variants, including basosquamous, keratotic, granular-cell, adamantinoid, clear-cell, and BCC with matrical differentiation, have also been described.

TREATMENT Superficial BCC is confined to or contiguous with the epidermis, and SCC in situ by definition does not invade the underlying dermis. Because of the lack of deeper invasion, these skin cancers are usually treated with a variety of destructive modalities, such as cryotherapy or electrodesiccation and curettage, that may yield cure rates for BCC of greater than 90%.

Hypopigmentation or atrophic scarring are common sequelae of these modes of treatment because of nonselective injury to surrounding healthy tissue.

Other methods of treatment, such as surgery or radiotherapy, may also produce visible scarring. Chemical destruction with 5-fluorouracil may result in good

cosmetic outcomes but initially may produce significant inflammation, resulting in decreased patient compliance with treatment.

IMIQUIMOD Imiquimod uses the body’s own immune system to fight certain skin diseases. It activates the immune cells in the body, leading to a localised increased immunity of the skin. This allows the skin to recognise and remove the diseased skin cells.

The immune response modifier, imiquimod, acts through Toll-like receptor (TLR)-7 (and to a lesser extent, TLR-8) signalling and has been shown to induce interferon (IFN-a) production in human blood cell cultures and when administered orally in humans. IFN-a appears to act upon natural killer (NK) cells and conventional dendritic cells (DCs) to stimulate IFN-c, tumour necrosis factor (TNF)-a, monocyte chemoattractant proteins (MCPs) and other cytokines. Locally, imiquimod stimulates the production of various cytokines at the cellular level that increase immunity and afford anticancer activity.

Overall, the cosmetic as well as clinical outcome of use of imiquimod is excellent.

Treatment of sBCC lesions involves application at night onto the affected area.

Apply for five nights per week (therefore having no treatment for the following two nights) and continue to complete a treatment programme for six weeks.

BCC is a hedgehog (HH)-driven malignancy with oncogenic gliomaassociated oncogene (GLI) signalling activated in a ligand-independent manner.

Imiquimod can also directly repress HH signalling by negatively modulating GLI activity in BCC and medulloblastoma cells.

Evidence suggests that the repressive effect of imiquimod on HH signalling is not dependent on TLR/MYD88 signalling.

These results suggest a mechanism for imiquimod engaging adenosine receptors (ADORAs) to control GLI signalling.

As explained by Gruber et al (2013), deregulated hedgehog (HH)/GLI signaling plays an aetiologic role in the initiation, progression and maintenance of many cancers. Small molecule targeting of HH signaling by inhibiting the essential pathway effector smoothened (SMO) has proven exceptionally efficient for the treatment of advanced and metastatic basal cell carcinoma. That said, severe side effects, limited response rates, SMO-independent GLI signaling and rapid development of drug resistance limit the therapeutic success of SMO antagonists, urgently calling for the identification of alternative and additional strategies repressing oncogenic HH signaling.

The authors highlighted findings showing that the Toll-like receptor-7/8 (TLR7/8) agonist imiquimod (imiquimod), an immune modulator approved for the treatment of BCC, can also act as a potent cell autonomous inhibitor of oncogenic HH signaling. Surprisingly, imiquimod reduces HH signal strength independent of TLR signaling, via adenosine receptor (ADORA)/Adenylate cyclase (AC)/Protein kinase A (PKA) activation. They highlight the molecular mechanisms of imiquimodmediated repression of HH/GLI and discussed the possible benefits as well as challenges of using ADORA agonists for the treatment of HH-associated cancer.

Pharmacological activation of ADORA with either an ADORA agonist or imiquimod resulted in a protein kinase A (PKA)mediated GLI phosphorylation and reduction in GLI activator levels. The activation of PKA and HH pathway target gene downregulation in response to imiquimod were abrogated by ADORA inhibition. Furthermore, activated Smoothened signalling, which positively signals to GLI transcription factors, could be effectively counteracted by imiquimod.

These results reveal a previously unknown mode of action of imiquimod in the treatment of BCC and also suggest a role for ADORAs in the regulation of oncogenic HH signalling.

Histological clearance rate Geisse et al (2004) showed a histological clearance rate of 82% (95% CI: 76%-87%) and 79% (95% CI: 73%-85%) for the five times per week and seven times per week in

MEDICAL CHRONICLE | April 2021 17

CPD | DERMATOLOGY

a) Superficial basal cell carcinoma on upper back

week in the imiquimod groups, respectively.

Two identical, multicentre, randomised, double-blind, vehicle-controlled, doseresponse studies were initiated at 55 centres in the US. All protocols and informed consent documents were submitted to and approved by each study centre’s institutional review board. Before study procedures were initiated, each subject voluntarily signed an informed consent form.

Subjects applied study cream to a single target sBCC once daily according to their assigned treatment regimen for six weeks and applied a small drop of study cream (approximately 4-7mm in diameter) based on the size of their sBCC. Each dose of cream was to be applied at approximately the same time of day, just prior to bedtime, and was to be rubbed into the lesion and the area approximately 1cm surrounding the lesion until the cream vanished. The cream was to remain on the skin for at least eight hours without occlusion, and was then removed with mild soap and water. The study indicates that imiquimod achieved an 82% histological clearance of sBCCs 12 weeks post treatment, and 94 % of patients showed initial histological clearance. Imiquimod showed a 93% NPV, which indicates that sBCCs responded well to treatment.

Sustained clearance The immune response modifier directly represses HH signalling by negatively modulating GLI activity. Apply five times a week for six weeks. This produces a good cosmetic result. Do not use for morphoeic BCC or pigmented BCC. It also shouldn’t be used in cases with immunosuppression.

A study by Jansen et al (2018), five-year results of a randomised controlled trial with 601 patients comparing effectiveness of 18 April 2021 | MEDICAL CHRONICLE

photodynamic therapy, topical imiquimod, and topical 5-fluorouracil in patients with sBCC, showed that 5% imiquimod cream is superior to both methyl aminolevulinate PDT and 5-fluorouracil cream in terms of efficacy. “We therefore consider 5% imiquimod cream as the first choice for noninvasive treatment in most primary superficial basal cell carcinomas,” the authors stated.

Multiple or large sBCCs There has been increasing interest in the use of 5% imiquimod cream in the treatment of patients with superficial basal cell carcinomas (sBCCs). To date, the reports of its efficacy apply to single tumours in individuals. However, in clinical practice it is common for patients to have more than one sBCC when they present for treatment.

The aim of this study was to assess the safety and efficacy of two dosing regimens of 5% imiquimod cream for the treatment of patients with multiple sBCCs. In a study by Shumack et al (2004) 67 adults with a total of 208 histologically confirmed sBCCs on their trunk, limbs, or neck (2-6 tumours per person) applied 5% imiquimod cream seven times per week or five times per week for six weeks. Twelve weeks after treatment, the tumour sites were examined clinically and histologically for evidence of residual tumour. In this study, patients had 2-6 tumours, 90% had 2-4 target tumours. In 77% of patients with multiple sBCCs, these were histologically cleared 12 weeks after treatment.

Cosmetic outcomes In Gollnick et al’s (2005) study, during the six-week treatment period, subjects or a caregiver applied imiquimod 5% cream five times per week (consecutive days),

b) Superficial basal cell carcinoma after 4 weeks of treatment with topical imiquimod

at approximately the same time of day by gently rubbing the cream on the tumour area and about 1cm around it until the cream disappeared. Safety evaluations consisted of physical examinations, vital sign measurements, clinical laboratory tests (haematology, blood chemistry, and urinalysis), pregnancy tests (where indicated for women of reproductive potential), and use of concomitant medications.

Local skin reactions (LSRs) of erythema, oedema, induration, vesicles, erosion, ulceration, scaling/flaking, and scabbing/crusting were assessed by the investigator at the target tumour site and in the surrounding area at each clinic visit, beginning with the initiation visit, and using a rating scale where 0 = none, 1 = mild, 2 = moderate, and 3 = severe. In addition, skin quality assessments were made at the target treatment site and surrounding area in order to assess cosmetic outcome.

Based on clinical evaluation, initial clearance rate for the ITT population was 89% at the 12-week posttreatment visit.

The clinical clearance rates did not appear to be influenced by such factors as age, skin type, target tumour size, number of baseline non-target tumours, or geographical location. In general, clinical response rates increased as LSR severity increased – 73%86% response with no LSRs. Approximately 80%-100% responded with mild LSRs; and 90% to 100% response with moderate or severe LSRs. Assessments demonstrated that all LSRs returned to baseline and remained stable. It will be important for physicians to communicate to patients that these LSRs are a normal and expected part of the treatment process but that the treatment is well tolerated by most patients.

These LSRs are commonly seen during treatment and may also prove to be useful in

predicting which patients will respond to imiquimod and achieve complete clearance of their sBCC. Only 1% of patients reported pain as a side effect, and as clearance rates increased so the LSRs decreased. It’s it essential for a good patient compliance and success of the treatment that patients are informed that erythema, erosion, scabbing/crusting will happen and that this is a sign that treatment is working.

Patients should take a rest period if they experience discomfit or if the erythema becomes excessive.

References Caperton, C et al. Safety, efficacy, and patient acceptability of imiquimod for topical treatment of actinic keratoses Clinical, Cosmetic and Investigational Dermatology 2011:4 35–40.

Wolff F et al. Imiquimod directly inhibits Hedgehog signalling by stimulating adenosine receptor/protein kinase A-mediated GLI phosphorylation Oncogene 2013:32, 5574–5581.

Gruber, W et al. An old friend with new skills: Imiquimod as novel inhibitor of Hedgehog signalling in basal cell carcinoma. Oncoscience 2014;9:567-573.

Jansen, M et al. Five-Year Results of a Randomized Controlled Trial Comparing Effectiveness of Photodynamic Therapy, Topical Imiquimod, and Topical 5-Fluorouracil in Patients with Superficial Basal Cell Carcinoma. Journal of Investigative Dermatology 2018: 138, 527e533; doi:10.1016/j.jid.2017.09.033.

Ooi, T, et al. Imiquimod-induced regression of actinic keratosis is associated with infiltration by T lymphocytes and dendritic cells: a randomized controlled trial. Br J Dermatol 2006 Jan;154(1):72-8.

Gollnick, H, et al. Recurrence rate of superficial basal cell carcinoma following treatment with imiquimod 5% cream: conclusion of a 5-year long-term followup study in Europe. Eur J Dermatol. 2008 NovDec;18(6):677-82.

Krawtchenko, N, et al. A randomised study of topical 5% imiquimod vs. topical 5-fluorouracil vs. cryosurgery in immunocompetent patients with actinic keratoses: a comparison of clinical and histological outcomes including 1-year follow-up. Br J Dermatol. 2007 Dec;157 Suppl 2:34-40.

Shumack S, et al. Efficacy of Topical 5% Imiquimod Cream for the Treatment of Nodular Basal Cell Carcinoma. Arch Dermatol 2002 trial.

ONLINE CPD

How treating sinus symptoms early can prevent a cough

In a Mayo Clinic study, researchers found that more than one-third of chronic cough patients given a CT scan had sinusitis.

"T

HIS STUDY SUGGESTS that sinusitis is more common than we had previously thought in people with chronic cough,” said Dr Lim Kaiser, lead researcher and Mayo Clinic pulmonologist and allergist. “It also confirms our impression in the chronic cough clinic that many of our patients have underlying sinus inflammation as a cause of their coughs. Our findings in this series of patients place sinusitis among the top three reasons for chronic cough, along with acid reflux and rhinitis, inflammation of the nasal passages.” Likewise, several factors lead to a persistent cough after a cold. A postnasal drip may irritate the upper airways, which are often more sensitive following an infection. Chronic cough is defined as a cough lasting over three weeks.

According to Dr Lim, sinusitis is often overlooked by physicians as a culprit in chronic cough. In addition, many patients had been told by their doctors to learn to live with their coughs.

SINUSITIS SYMPTOMS Acute and chronic sinusitis cause similar symptoms and signs, including purulent rhinorrhoea, pressure and pain in the face, nasal congestion and obstruction, hyposmia, halitosis, and productive cough (especially at night). Often the pain is more severe in acute sinusitis. The area over the affected sinus may be tender, swollen, and erythematous. Sinusitis can manifest as weeping mucus that drips down the throat, which can cause irritation and prompt coughing. Previously, doctors have often lumped sinusitis and its symptoms together with postnasal drip syndrome from rhinitis as a potential cause of chronic cough, said Dr Lim. “But this is a problem, as the treatment for rhinitis is not the same as for sinusitis,” he says. “Medications designed for rhinitis do not penetrate into the sinuses very well.”

TREATMENT Dr Lim advocates intensive treatment for sinusitis in chronic coughers. “If the cough doesn't go away, it's probably the wrong diagnosis or it has not been treated adequately,” he says.

• Postnasal drip • Pneumonia.

In chronic cough, the most common causes are • Chronic bronchitis • Postnasal drip, which is often the result of sinusitis

This is a summary of a CPD-accredited article available on www.medicalacademic.co.za

• Airway hyperresponsiveness after resolution of a viral or bacterial respiratory infection (ie, postinfection cough) • Gastroesophageal reflux • Chronic obstructive pulmonary disease.

component to their cough. Also, protracted coughing may injure the bronchial mucosa, which may trigger more coughing.

Treatment is management of the cause.

Patients with chronic cough may develop a secondary reflex or psychogenic

References available on request.

Tried and trusted cold and flu treatment for the whole family:

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Indicated for the alleviation of cough Cough suppressant, expectorant and antihistamine properties Raspberry flavoured

Indicated for the relief of symptoms associated with colds and influenza such as nasal congestion, headache, minor aches and pains A 6-in-1 combination with analgesic, decongestant and antihistamine properties 2 pain relievers: Paracetamol and Salicylamide Contains 50 mg of Ascorbic acid (Vitamin C)

MANAGING A COUGH After a cold or due to sinusitis, some coughs last weeks or months. That could be because coughing irritates the lungs, which leads to more coughing.

Cough is an explosive expiratory manoeuvre that is reflexively or deliberately intended to clear the airways. It is one of the most common reasons that people see their GP. In acute cough, the most common causes are: • Upper respiratory infection, including acute bronchitis

S2 FLUTEX Cold and Flu capsules with Vitamin C. Ref. No.: G1221 (Act 101/1965).

Each capsule contains chlorphenamine maleate 2 mg, phenylephrine hydrochloride 2 mg, paracetamol 100 mg, salicylamide 75 mg, ascorbic acid 50 mg and caffeine anhydrous 30 mg. S2 FLUTEX Co Linctus. Reg. No.: F/10.1/162. Each 5 ml syrup contains codeine phosphate 7,5 mg, diphenhydramine hydrochloride 12,0 mg and ammonium chloride 100,0 mg. S1 FLUTEX Junior Cold and Flu Syrup. Ref. No.: B851 (Act 101/1965). Each 5 ml of syrup contains phenylephrine HCl 3,5 mg and paracetamol 125,0 mg. For full prescribing information refer to the professional information approved by the medicines regulatory authority (FLUTEX Cold and Flu 09/2010; FLUTEX Co Linctus 09/2010; FLUTEX Junior Cold and Flu Syrup 08/1976). Trademarks are owned by or licenced to the Aspen Group of companies. © 2020 Aspen Group of companies or its licensor. All rights reserved. Marketed

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MEDICAL CHRONICLE | April 2021 19

CLINICAL | GASTROENTEROLOGY

Managing pancreatic

exocrine insufficiency Pancreatic exocrine insufficiency or exocrine Pancreatic insufficiency (EPI) is a condition characterised by deficiency of the exocrine pancreatic enzymes, resulting in the inability to digest food properly, or maldigestion.

E

PI IS ASSOCIATED with certain diseases and conditions that affect the pancreas, such as cystic fibrosis, partial pancreatectomy and chronic pancreatitis.

W

HA T’S

ON

Patients with EPI can’t properly digest fats, proteins and carbohydrates. In addition to preventing adequate digestion, EPI produces uncomfortable gastrointestinal (GI) symptoms.

YOU R

SYMPTOMS The most common symptom of PEI is fatty stools (steatorrhoea). This occurs when the digestive system is unable to absorb dietary fats. Instead, these fats pass through the

ro t e i n PL ATE... fats | carbohydrates | p

s

intestinal tract with waste products.

The stools tend to be oily, large, pale, very foul-smelling, and often float in toilet water and stay in the toilet bowl, even after flushing. Individuals with steatorrhoea sometimes experience faecal incontinence or oily leakage. Intestinal gas and bloating can also occur from the fermentation of undigested food in the colon.

Many individuals with PEI will experience nutritional deficiencies, since they are not taking in enough fats to help absorb vitamins. PEI can also cause weight loss, because patients do not get enough calories from the food they eat. Weight loss is more common in those who have PEI in addition to a digestive disease, such as Crohn’s disease. Some symptoms of nutrient malabsorption, and their typical causes, include fatigue, anaemia, bone disease (vitamin D deficiency), bleeding disorders, problems forming clots, bleeding under the skin, and blood in the faeces or urine (vitamin K deficiency).

PEI MANAGEMENT It is important to treat the underlying cause of PEI, and these treatments will vary depending on the cause. However, lifestyle changes make it easier for the body to break down and absorb nutrients, which can help reduce the steatorrhoea and nutritional deficiencies that PEI causes.

PANCREATIC EXOCRINE INSUFFICIENCY (PEI) Improve the interdigestive “house keeper” function of gastrointestinal motility and biliopancreatic secretion1

Pancreatic exocrine insufficient patients who experience weight loss, those with daily fecal fat excretion of more than 15 g under a diet containing

CREON®, THE PANCREATIC ENZYME SUBSTITUTE2,3

100 g fat daily, and those with relevant steatorrhea related symptoms are classically and generally considered as suitable candidates for enzyme substitution therapy1

References: 1. Domínguez-Muñoz JE. Pancreatic exocrine insufficiency: diagnosis and treatment. J Gastroenterol Hepatol 2011;26 Suppl 2:12–16.2. 2. Creon® 25000. Approved package insert February 2016. 3. Creon® 10000.

Approved package insert September 2005.

S1 Creon® 10000. Each capsule contains enteric coated granules of Pancreatin 150 mg. Registration Numbers: Namibia: 04/11.1/1015, South Africa: 33/11.1/0340.

S1 Creon® 25000. Each capsule contains enteric coated granules of Pancreatin 300 mg. Registration Numbers: Namibia: 04/11.1/1016, South Africa: 28/11.1/0645.

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ENZYME THERAPY The most effective treatment for PEI is pancreatic enzyme replacement therapy (PERT), which involves taking pancrelipase to provide the body with enzymes that break down fats and proteins. Those with PEI must take PERT with each meal or snack that contains fat and/or protein. When taken with food, PERT duplicates the normal digestive process because the enzymes mix with the food and help absorption.

PEI OUTLOOK With pancreatic enzyme replacement therapy and some changes to dietary adjustments, patients can manage symptoms of pancreatic exocrine insufficiency.

References The National Pancreas Foundation. https:// pancreasfoundation.org/, assessed 26 March 2021.

GI Society. https://badgut.org/, accessed 26 March 2021.

CLINICAL | WOMEN'S HEALTH

SA's latest innovation in emergency contraception

Emergency contraception offers patients a second chance to prevent pregnancy when primary prophylaxis fails, or in emergency cases.

D

R LARISSE BADENHORST recently presented a webinar on the topic, hosted by Pharmacy Magazine and sponsored by Actor Pharma, which as the launch of their new molecule, ulipristal acetate 30mg. Dr Badenhorst is the co-owner of My Sexual Health (MSH) and Well Family Practice in Bryanston, Johannesburg. Although ovulation occurs during the 24-36 hours after luteinising hormone (LH) peak, the timing of ovulation may vary considerably from cycle to cycle, even in women with regular cycles.

“Unprotected sexual intercourse always carries a risk of pregnancy regardless of the day of the cycle because the timing of ovulation cannot reliably be predicted,” Dr Badenhorst cautioned.

“Normal spermatozoa can survive in the female reproductive tract and retain the ability to fertilise an egg for up to five days,” she said. “This is particularly important to understand in the context of when ovulation occurs and how long the risk of pregnancy is there.

ovulation, but, the big difference is that the efficacy of LNG is only within 72 hours, whereas UPA is effective for 120 hours after unprotected sex. This difference is due to UPA having a more potent effect on inhibiting follicular rupture. UPA inhibits

ovulation in the pre-ovulatory phase, which is when the risk of pregnancy is highest. Another difference is that LNG is a progesterone receptor agonist (progestin), where UPA is a PR modulator.

“It’s important to remember that

regardless of which EC is used, if it is taken after the pre-ovulatory peak of LH it’s not going to work,” said Dr Badenhorst.

For more information or to watch the replay of the webinar visit: https://tinyurl.com/3c5wcn4h

The timing of ovulation may vary considerably from cycle to cycle ULIPRISTAL ACETATE “A synthetic selective progesterone receptor modulator (SPRM), ulipristal acetate (UPA) acts via high-affinity binding to the human progesterone receptor, which then modifies the activity of the natural progesterone. So, it prevents that natural progesterone from occupying that receptor. As an emergency contraceptive, it inhibits or delays ovulation by suppressing the surge that we see in the menstrual cycle.

“When taken immediately before ovulation is scheduled to occur, it actually postpones follicular rupture, which can take up to five days. This is where UPA is very good at acting as it delays the rupture for at least five days in 78% of cases, according to the studies done. So, it acts for five days, therefore covering the 24-36 days of ovulation,” explained Dr Badenhorst. “It is not an abortifacient like mifepristone. Although it acts in the same way, mifepristone actually binds to prostaglandins to have this effect whereas UPA doesn’t bind to prostaglandins and therefore does not cause abortions.”

ADVANTAGES OF UPA “So, why use UPA instead of levonorgestrel (LNG), which is currently available on the market?” Dr Badenhorst asked. “LNG is also a morning-after pill and it also inhibits MEDICAL CHRONICLE | April 2021 21

CLINICAL | WINTER AILMENTS

A recap of LRTIs Lower respiratory tract infections (LRTIs) are any infections in the lungs or below the voice box. These include pneumonia, bronchitis and tuberculosis.

L

RTIs CAN AFFECT the airways, such as with bronchitis, or the air sacs at the end of the airways, as in the case of pneumonia.

LRTI is a broad terminology which includes acute bronchitis, pneumonia, acute exacerbations of chronic obstructive

pulmonary disease/chronic bronchitis (AECB), and acute exacerbation of bronchiectasis. Acute LRTIs (ALRTIs) are one of the common clinical problems in community and hospital settings.

Management of community-acquired pneumonia (CAP) and AECB may pose

challenges because of the difficulty in differentiating infections caused by typical and atypical microorganisms and rising rates of antimicrobial resistance. Beta-lactam antibiotics, macrolides, and fluoroquinolones are routinely prescribed medicines for the management of ALRTIs.

KEEPING SUPERHEROES STRONG

Providing clinical and bacteriological efficacy1 KLACID® IN ADULTS2-4

KLACID® IN CHILDREN2-4

Sinusitus

Acute otitis media

Pharyngitis

Pharyngitis and tonsillitis

Lower respiratory tract infections

Lower respiratory tract infections

Acute exacerbatations of chronic bronchitis caused by infectious bacteria

Skin and soft tissue infections due to S. Aureus

References: 1. Langtry HD, Brogden RN. Clarithromycin. A Review of its Efficacy in the Treatment of Respiratory Tract Infections in Immunocompetent Patients. Drugs 1997;53(6):973-1004. 2. KLACID® P125/P250 Granules for Oral Suspension package insert. 7 July 2006. 3. KLACID® XL Modified release tablets package insert. 1 December 2006. 4. KLACID® I.V. Lyophilised Powder for Injection package insert. 1 December 2006.

S4 KLACID® P125 Granules for Suspension. Granules are supplied in 50 ml bottles. After suspension, each 5 ml of KLACID® P125 contains 125 mg clarithromycin. Reg. No.: 28/20.1.1/0035. Botswana: S2 Reg. No.: BOT9900333; Kenya: POM, Reg. No.: H98/208; Mauritius: Reg. No.: R4134/02/16; Namibia: NS2 Reg. No.: 04/20.1.1/1269; Uganda: POM, Reg. No: 2469/06/98; Zambia: Reg. No: 128/004; Zimbabwe: PP Reg. No.: 2000/7.2.5/3797. S4 KLACID® P250 Granules for Suspension. Granules are supplied in 50 or 100 ml bottles. After suspension, each 5 ml of KLACID® P250 contains 250 mg clarithromycin. Reg.No.: 29/20.1.1/0190. Botswana: S2 Reg.No.: BOT9900334; Kenya: POM, Reg.No.: H98/258; Mauritius: Reg.No.: R3362/02/16; Namibia: NS2 Reg.No.: 04/20.1.1/1270; Nigeria: POM, Reg.No.: 04-3449; Uganda: POM, Reg.No.: 2470/06/98; Zambia: Reg. No.: 128/005; Zimbabwe: PP, Reg. No.: 2000/7.2.5/3798. S4 KLACID® XL Modified release tablets. KLACID® XL is supplied in blister packs of 5 and 10 tablets. Each tablet contains 500 mg clarithromycin. RegNo.: 31/20.1.1/0379. Botswana: S2 Reg.No.: BOT0100451; Kenya: POM, Reg.No: H2001/0072; Malawi: Reg.No.: PMPB/PL147/13; Mauritius: Reg.No.: R3363/02/16; Namibia: NS2 Reg. No.: 04/20.1.1/1271; Nigeria: POM, Reg. No.: 04-4407; Sudan: Reg. No.: PL 00037/0275; Uganda. POM, Reg. No.: 5977/06/07; Zimbabwe: PP. Reg. No.: 98/7.2.5/3451. S4 KLACID® I.V. Lyophilised Powder for Injection. KLACID® I.V. Lyophilised Powder for Injection is supplied in clear glass vials with a capacity of 15 ml. Each vial contains 500 mg clarithromycin. Reg. No.: 28/20.1.1/0264. Kenya: POM, Reg. No.: H98/207; Mauritius: Reg. No.: R4133/02/14; Zimbabwe: PP, Reg. No.: 2001/7.2.5/3956.

For Full Prescribing Information Refer to the Package Insert Approved by the Medicines Regulatory Authority.

Date of Publication of this Promotional Material: March 2021. Promotional Material Reference Number: SAF2183028.

Abbott Laboratories S.A. (Pty) Ltd, Reg. No: 1940/014043/07. Abbott Place, 219 Golf Club Terrace, Constantia Kloof, 1709. Tel: +27 11 858 2000.

22 April 2021 | MEDICAL CHRONICLE

Macrolide antibiotics are tried and tested, and effective agents for the treatment of LRTIs. Clarithromycin, a macrolide, offers several benefits in the management of ALRTIs. Risk factors that make a person more likely to develop a lower respiratory tract infection include: • A recent cold or flu • A weakened immune system • Being more than 65 years old • Being under five years old • Recent surgery.

DIAGNOSIS A diagnosis is made during an exam and after discussing the symptoms the patient has and how long they have been present.

Tests to help diagnose the problem include: • Pulse oximetry • Chest X-rays to check for pneumonia • Blood tests to check for bacteria and viruses • Mucus samples to look for bacteria and viruses.

UPPER vs LOWER RESPIRATORY TRACT INFECTIONS LRTIs differ from upper respiratory tract infections by the area of the respiratory tract they affect.

While lower respiratory tract infections involve the airways below the larynx, upper respiratory tract infections occur in the structures in the larynx or above.

People who have LRTIs will experience coughing as the primary symptom.

Patients with upper respiratory tract infections will feel the symptoms mainly above the neck, such as sneezing, headaches, and sore throats. They may also experience body aches, especially if they have a fever.

Lower respiratory tract infections include: • Bronchitis • Pneumonia • Bronchiolitis • TB. Upper respiratory tract infections include: • Common colds • Sinus infections • Tonsillitis • Laryngitis.

Flu infections can affect both the upper and lower respiratory tracts.

References Mahashur A. Management of lower respiratory tract infection in outpatient settings: Focus on clarithromycin. Lung India 2018;35:143-9 Medical News Today. Medically reviewed by Alana Biggers, M.D., MPH — Written by Jenna Fletcher on February 11, 2019. Accessed 26 March 2021.

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Dr Di Hawarden is the immediate past chairperson of ALLSA. (Allergy Society of South Africa) She has served on the committee since 2001. Dr Hawarden worked at the allergy clinic at Groote Schuur Hospital and Red Cross Children’s Hospital from January 2000 to October 2018. In addition, she had a private practice at UCT Lung Institute, where she saw private adult and paediatric allergy patients. Di is an enthusiastic examiner, convenor and moderator of the Diploma in Allergy run through the CMSA. Together with Professor Weinberg, she is the editor of Current Allergy and Clinical Immunology. (CACI) Di and Dr Shaunagh write the popular ABC of Allergy which appears in each edition of the journal. She has published in local and international journals, and writes a section for the South African Medicine Formulary. (SAMF)

MEDChronicle

MEDICAL CHRONICLE | April 2021 23

CLINICAL | GASTROENTEROLOGY

Multi-Matrix 5-ASA

to induce remission in ulcerative colitis?

The development of new technologies for ulcerative colitis such as the matrix form of 5-aminosalicylic acid or mesalazine has already shown efficacy over placebo, but not over coated tablet form, which is usually used in clinical protocols for this disease management.

U

LCERATIVE COLITIS (UC) is an inflammatory bowel disease, whose symptoms are associated to episodes of bloody diarrhoea and intense

abdominal pain. The treatment of UC patients is based on a diet that aims at constipating the gastrointestinal tract in order to reduce evacuation frequency, as

well as the use of drugs that may induce the disease remission and control symptoms.

Among drugs, 5-aminosalicylic acid (5ASA) or mesalazine has been extensively

Prolonged release mesalazine for patients with mild-to-moderate ulcerative colitis1,2

2

Mezavant® is a valuable option in the management of patients with mild to moderate ulcerative colitis1

MMX® TECHNOLOGY FOR PROLONGED DRUG RELEASE2-5

DELIVERS MESALAZINE (5-ASA) THROUGHOUT THE COLON2-5

ALWAYS ONCE DAILY2

HIGH-DOSE FORMULATION REDUCES THE DAILY TABLET BURDEN1

IMPROVED ADHERENCE TO TREATMENT6

MEZAVANT IS INDICATED FOR:2 The treatment and maintenance of remission in ulcerative colitis The approved Mezavant professional information should be consulted before prescribing.

5-ASA: 5-acetyl salicylic acid References: 1. Yang LPH, McCormack PL. MMX® Mesalazine: A review of its use in the management of mild to moderate ulcerative colitis. Drugs 2011;71(2):221-235. 2. Mezavant approved package insert, August 2013. 3. Brunner M, Assandri R, Kletter K, Tschurlovits M, Corrado Me, Villa R, et al. Gastrointestinal transit and 5-ASA release from a new mesalazine extended-release formulation. Aliment Pharmacol Ther.

2003;17:395–402. 4. Tenjarla S, Romasanta V, Zeijdner E, Villa R, Moro L. Release of 5-aminosalicylate from an MMX mesalamine tablet during transit through a simulated gastrointestinal tract system. Advances in Therapy 2007;24(4):826-840. 5. Tenjarla S, Abinusawa A. In-vitro characterization of 5-aminosalicylic acid release from MMX mesalamine tablets and determination of tablet coating thickness. Adv Ther 2011;28(1):6272. 6. Simoni SE, Felipsen SF, Conegero Sanches AC, Vasconcelos HL. Multi-Matrix 5-Aminosalicylic Acid Efficacy in Induction of Remission in Mild-to-Moderate Ulcerative Colitis: A Systematic Review. International Journal of Health Sciences, September 2019;7(3): 42-51.

Mezavant® (enteric coated, prolonged release tablet.) Each tablet contains mesalazine 1 200 mg. Reg. No. 45/11/0463. For full prescribing information refer to the professional information approved by the medicines regulatory authority.

To report an Adverse Event, e-mail Adcock.AEReports@adcock.com or call 011 635 0134 To request a copy of the current approved professional information or references, e-mail:Helpdesk.MedicalAffairs@adcock.com ©2019 Shire. All rights reserved. SHIRE and the Shire logo are registered trademarks of Shire Pharmaceutical Holdings Ireland or its affiliates Adcock Ingram Limited. Reg. No. 1949/034385/06. Private Bag X69, Bryanston, 2021, South Africa.

Telephone + 27 11 635 0000. www.adcock.com. 16538J. 202102241089543. C-APROM/ZA/MEZ/0003.

24 April 2021 | MEDICAL CHRONICLE

taken since there is a better safety profile when compared with corticosteroids or immunosuppressants.

Action mechanism of mesalazine has not been established yet, but it is known that, besides inhibiting cyclooxygenase type 2, mesalazine can inhibit leukocyte’s mobility. It has antioxidant properties; it is able to prevent mitochondrial damage and it inhibits some transcription factors of proinflammatory substances such as NF-Kb9.

The dose and pharmaceutical form have the main role on aminosalicylates’ efficacy, especially 5-ASA. Among the available ones, coated tablet is the most widely taken during UC-patients’ treatment. However, innovative formulations such as MultiMatrix System (MMX) have already proved their efficacy against placebos with the maintenance of beneficial effects up to 12 months.

Background and Aim: This trial aimed at carrying out a systematic review to gather evidence that can reveal pre-eminence or equivalence in efficacy and safety of the matrix form of 5-aminosalicylic acid or mesalazine and the coated tablet form in induction of remission in mild to moderate ulcerative colitis.

Results: Three studies met inclusion criteria and results have demonstrated that similar levels of endoscopic remission were achieved in both forms of the drug. However, clinical remission rates have suggested better results when mesalazine matrix was used. On the other hand, adverse effects were similar in both formulations, with headache and gastrointestinal disorders as the most representative ones.

Conclusion: During this study, it could be observed that multi-matrix technology was well supported, since the efficacy on 5-ASA MMX tablets is very similar to the one on the conventional coated tablet, but the matrix technology points out better results in the remission parameters clinic. In addition, safety profile of both dose forms was also equivalent.

However, choosing matrix technology as the main way to combat UC is still controversial due to the high cost of this pharmaceutical form.

It was concluded that there are insufficient clinical studies to demonstrate the superiority of 5-ASA multi-matrix when compared with coated tablet during ulcerative colitis treatment.

References Simoni S, Felipsen S, Sanches A et al. Multi-Matrix 5-Aminosalicylic Acid Efficacy in Induction of Remission in Mild-to-Moderate Ulcerative Colitis: A Systematic Review. International Journal of Health Sciences 2019:3:42-51. DOI: 10.15640/ijhs.v7n3a4.

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*platelet activating factor. †based on once a day dosing. §Allergic Rhinitis References: 1. Ridolo E, et al. Rupatadine for the treatment of allergic rhinitis and urticaria: a look at the clinical data. Clin Invest 2014;4(5):453-461. 2. Picado C. Rupatadine: pharmacological profile and its use in the treatment of allergic disorders. Exp Opin Pharmacother. 2006;7(14):1989-2001.

3. Potter P, et al. Rupatadine oral solution in children with persistent allergic rhinitis: A randomized, double-blind, placebo-controlled study. Pediatr Allergy Immunol. 2013;24(2):144-150. 4. Potter P, et al. Rupatadine is effective in the treatment of chronic spontaneous urticaria in children aged 2–11 years. Pediatr Allergy Immunol. 2016;27(1):55-61. 5. Valle M, et al. PD39 - Application of population pharmacokinetic modeling and simulation in the design of the optimal dose regime of rupatadine in children 2-5 year old children. Clin Transl Allergy 2014;4(Suppl 1):P39. 6. RUPANASE Junior approved package insert, June 2020.

S2 Proprietary name and dosage form: RUPANASE® Junior Oral Solution. Composition: Each mℓ of oral solution contains: 1 mg rupatadine (as fumarate). Registration number: 50/5.7.1/0569. Name and business address of applicant: iNova Pharmaceuticals (Pty) Ltd, Co. Reg. No. 1952/001640/07, 15e Riley Road, Bedfordview. Tel. No. 011 087 0000. www.inovapharma.co.za. For full prescribing information, refer to the package insert as approved by the SAHPRA (South African Health Products Regulatory Authority). Further information is available on request from iNova Pharmaceuticals. 16397L. IN4135/21.

CLINICAL | PSYCHIATRY

Dr Marshinee Naidoo

Can Covid-19 cause depression?

New research suggests the virus may significantly increase chances of developing a psychiatric disorder.

M

ANY SOUTH AFRICANS will be aware that the stress of the Covid-19 pandemic, the earlier lockdown and ongoing restrictions associated with it can potentially have an impact on mental wellness and may have been advised on what they could do to mitigate it. But what of those who are actually infected by the virus; can the infection have an impact on the brain and result in mental conditions such as depression?

Dr Marshinee Naidoo, a psychiatrist who practises at Akeso Alberton mental health facility in Johannesburg, says that mental health practitioners have for some time suspected that there may be a link between the novel coronavirus and the development of mental health problems in individuals, but the latest medical studies now appear to confirm it.

“There is much about the virus and its behaviour that is as yet unknown, and researchers are still working to establish exactly how Covid-19 may impact the mind and functioning of the brain. However, this new research suggests that people who have been ill with Covid-19 had a significant chance of developing a psychiatric disorder while battling the infection and even after recovering,” she says.

According to Dr Naidoo, a recent study published in The Lancet medical journal in November 2020, found that 18% of Covid-19 patients developed a mental health condition such as depression, anxiety, or dementia, within three months of diagnosis. They also had double the risk of those individuals who did not contract the virus.1 A recent survey from Ecuador,

26 April 2021 | MEDICAL CHRONICLE

meanwhile, suggests that people diagnosed with Covid-19 commonly experience depression, anxiety, insomnia and posttraumatic stress disorder.2 “There is growing evidence that Covid-19 can affect the brain and mind of some individuals, increasing the risk of a range of psychiatric illnesses,” comments Dr Naidoo.

The Lancet study, which evaluated the health records of more than 62 000 people diagnosed with Covid-19 in the United States, suggests that nearly 6% of adults diagnosed with Covid-19 developed a psychiatric disorder, for the first time ever, within 90 days. This compared to just 3.4% of patients who did not have Covid-19. This means that those who developed Covid-19 had twice the risk of developing a mood or anxiety disorder for the very first time.

“Being diagnosed with a potentially life-threatening illness such as Covid-19 can in itself be extremely stressful. Those individuals who test positive for the virus also have to isolate themselves, which can impact their mental health. And while patients would usually look to loved ones for support while they recover, they are not able to in the case of Covid-19 infection as they need to avoid transmitting the infection.

They therefore lack this most important means of support,” explains Dr Naidoo.

“Many Covid-19 patients, known as the ‘long haulers’, may have a range of debilitating physical symptoms that can last for many months and severely impact their daily lives. This can place additional stressors on them, including difficulties returning to their normal activities such as work, or child-minding,” she adds.

“In addition to the isolation involved, Covid-19 diagnosis and treatment are more likely to be traumatic than it is for many other medical conditions, due to the potential severity of the illness and the lack of certainty regarding its treatment and outcome.”

According to Dr Naidoo, all of these factors mean that infection can potentially have a considerable impact on the mental health of the individual who has experienced Covid-19 infection with moderate to severe symptoms, and those with preexisting medical conditions may be particularly vulnerable to having an existing mental health condition exacerbated by an infection.

She says that there is, however, an additional aspect to being ill with the virus.

Medical science has shown that Covid-19 is not necessarily just a respiratory illness but that the disease also often impacts other organs, including the brain.

“Medical researchers are still working to understand how the virus interacts with the brain and the central nervous system, but they suspect that it may in some cases inflame and cause damage to the blood supply system and lead to swelling of the brain. If the virus impacts the central nervous system in such a way, this could certainly potentially result in a psychiatric illness of one kind or another.

“Indeed, some studies show that Covid-19 patients frequently experience neurological complications, such as dizziness, confusion, delirium and other cognitive problems. A person’s sleep patterns can also be affected. This may

in turn lead to insomnia, and develop into depression, anxiety, or other mental health disorders,” notes Dr Naidoo.

“Remember that it is normal for anyone to feel down at times, but a major depressive episode lasts at least a month. If patients are constantly distracted from their normal roles, like work or family life, and lose interest in activities that they previously enjoyed even after recovery from Covid-19, it may be a sign of a more serious mental health condition.”

“Maintaining a healthy diet and sleep schedule, and as far as possible trying to stay physically active, can also assist in supporting mental health. Patients can also try relaxation techniques, such as mindful meditation and deep breathing.

Also remember that recovery from Covid-19 can take weeks and, in some cases, even months. Understanding this can assist to reduce anxiety and assist in supporting mental health,” she concludes.

References and further reading 1. Taquet, M; Luciano, S; Geddes, JR; Harrison, PJ, 2020. Bidirectional associations between COVID-19 and psychiatric disorder: retrospective cohort studies of 62 354 COVID-19 cases in the USA. The Lancet Psychiatry published 9 November 2020. Accessed 7 February 2021.

Full text available at https://www.thelancet.com/ journals/lanpsy/article/PIIS2215-0366(20)30462-4/ fulltext 2. Paz, C; Mascialino, G; Adana, L; Rodriguez, A, 2020.

Anxiety and depression in patients with confirmed and suspected COVID-19 in Ecuador. Psychiatry and Clinical Neurosciences 74(10) July 2020. Full text available at https://www.ncbi.nlm.nih.gov/pmc/articles/ PMC7361296/pdf/PCN-9999-na.pdf

Prolonged release mesalazine for patients with mild-to-moderate ulcerative colitis1,2

2

Mezavant® is a valuable option in the management of patients with mild to moderate ulcerative colitis1

MMX® TECHNOLOGY FOR PROLONGED DRUG RELEASE2-5

DELIVERS MESALAZINE (5-ASA) THROUGHOUT THE COLON2-5

ALWAYS ONCE DAILY2

HIGH-DOSE FORMULATION REDUCES THE DAILY TABLET BURDEN1

IMPROVED ADHERENCE TO TREATMENT6

MEZAVANT IS INDICATED FOR:2 The treatment and maintenance of remission in ulcerative colitis The approved Mezavant professional information should be consulted before prescribing.

5-ASA: 5-acetyl salicylic acid References: 1. Yang LPH, McCormack PL. MMX® Mesalazine: A review of its use in the management of mild to moderate ulcerative colitis. Drugs 2011;71(2):221-235. 2. Mezavant approved package insert, August 2013. 3. Brunner M, Assandri R, Kletter K, Tschurlovits M, Corrado Me, Villa R, et al. Gastrointestinal transit and 5-ASA release from a new mesalazine extended-release formulation. Aliment Pharmacol Ther. 2003;17:395–402. 4. Tenjarla S, Romasanta V, Zeijdner E, Villa R, Moro L. Release of 5-aminosalicylate from an MMX mesalamine tablet during transit through a simulated gastrointestinal tract system. Advances in Therapy 2007;24(4):826-840. 5. Tenjarla S, Abinusawa A. In-vitro characterization of 5-aminosalicylic acid release from MMX mesalamine tablets and determination of tablet coating thickness. Adv Ther 2011;28(1):62-72. 6. Simoni SE, Felipsen SF, Conegero Sanches AC, Vasconcelos HL. Multi-Matrix 5-Aminosalicylic Acid Efficacy in Induction of Remission in Mild-to-Moderate Ulcerative Colitis: A Systematic Review.

International Journal of Health Sciences, September 2019;7(3): 42-51.

Mezavant® (enteric coated, prolonged release tablet.) Each tablet contains mesalazine 1 200 mg. Reg. No. 45/11/0463. For full prescribing information refer to the professional information approved by the medicines regulatory authority.

To report an Adverse Event, e-mail Adcock.AEReports@adcock.com or call 011 635 0134 To request a copy of the current approved professional information or references, e-mail:Helpdesk.MedicalAffairs@adcock.com ©2019 Shire. All rights reserved. SHIRE and the Shire logo are registered trademarks of Shire Pharmaceutical Holdings Ireland or its affiliates Adcock Ingram Limited. Reg. No. 1949/034385/06. Private Bag X69, Bryanston, 2021, South Africa.

Telephone + 27 11 635 0000. www.adcock.com. 16538J. 202102241089543. C-APROM/ZA/MEZ/0003.

CLINICAL | WOMEN'S HEALTH

Postpartum complications increased in women with PCOS

Women with polycystic ovary syndrome (PCOS) are at a higher risk of cardiometabolic and psychiatric comorbidities and preconception and antepartum complications, but the impact of polycystic ovary syndrome during the postpartum period is unknown.

P

COS IS THE most common endocrine disorder affecting women of reproductive age, with worldwide prevalence estimated at up to 13%. It is characterised by the presence of two of three diagnostic criteria: irregular menses, clinical or biochemical hyperandrogenism, and polycystic-appearing ovaries, and

also has well recognised associations with several cardiovascular disease (CVD) risk factors, including type 2 diabetes, obesity and lipid abnormalities. Furthermore, it has also been shown to be associated with increased risk of psychiatric disorders, in particular depression and anxiety, and with complications during pregnancy. Notably,

a history of depression before pregnancy is a recognised risk factor for perinatal depression, the most common medical problem during pregnancy, occurring in one in seven patients, and which is associated with significant adverse infant and maternal outcomes. Obstetrical complications of PCOS include gestational

DYDROGESTERONE HAS ENHANCED PROGESTOGENIC EFFECTS1

SINCE 1960, IT HAS BEEN SUPPORTING GENERATIONS OF WOMAN2

- (MAT 03 2020) IQVIA data

References: 1. Schindler AE, Campagnoli C, Druckmann R, et al. Classification and Pharmacology of progestins. Maturitas 2008;61(1-2):171-180. ® 2. Abbott, data on file, date of Duphaston first global approval.

S4 Duphaston® 10 mg tablets. Each tablet contains 10 mg dydrogesterone. Registration number: South Africa: S/21.8.2/165.

For full prescribing information refer to the package insert approved by the Medicines Regulatory Authority.

Date of Publication of this promotional material: March 2021. Promotional Review Number: SAF2183175.

Abbott Laboratories S.A. (Pty) Ltd. Co. Reg. No. 1940/014043/07. Abbott Place, 219 Golf Club Terrace, Constantia Kloof, 1709. Tel: +27 11 858 2000.

28 April 2021 | MEDICAL CHRONICLE

diabetes (odds ratio, OR 3.43), pregnancyinduced hypertension (OR 3.07) and preeclampsia (OR 3.28), which further contribute to long-term cardiometabolic risk. This is important, because almost 70% of pregnancy-related deaths in the general population occur at delivery or within the first year postpartum, with CVD and stroke accounting for over one third of deaths.

To date, there are no studies in women with PCOS specifically targeting the postpartum period (defined as four-six weeks after delivery). To address this, a study by Alur-Gupta et al (2021) compared the prevalence rates of postpartum cardiovascular complications and perinatal and postpartum depression in 42 391 women with PCOS to those in 795 480 women without PCOS. This was a retrospective cohort study conducted using a United States insurance claims database. Women with and without polycystic ovary syndrome aged 18 to 50 years enrolled continuously in a single health plan during the preconception, antepartum, and postpartum periods between 2000 and 2016 were included.

The primary outcome was postpartum cardiovascular disease and depression (perinatal and postpartum).

Comparisons were adjusted for covariates including age, geographic location, preterm delivery, assisted reproductive technology use, multiple births, prepregnancy depression, prepregnancy diabetes, prepregnancy hypertension, gestational diabetes, gestational hypertension, obesity, history of hyperlipidaemia, smoking and race. In comparison to women without PCOS, PCOS was associated with significantly higher odds of CVD complications, as well as both perinatal and postpartum depression.

In comparison to nonobese women without PCOS, nonobese women with PCOS had higher odds of postpartum eclampsia, peripartum cardiomyopathy and cerebrovascular accidents. In women without a history of depression before pregnancy, the presence of PCOS increased the odds of perinatal depression (OR 1.32) and postpartum depression (OR 1.5).

CONCLUSION The found that women with polycystic ovary syndrome are at increased risk of both cardiovascular and psychiatric complications during the postpartum period. PCOS should be recognised as an at-risk condition. These findings underscore the need for routine screening and early interventions for these major comorbidities.

Reference Alur-Gupta S, Boland MR, Barnhart KT, et al.

Postpartum complications increased in women with polycystic ovary syndrome. Am J Obstet Gynecol 2021;224:280.e1-13

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Dr Leony Fourie is a lecturer at WITS University and Head of Colorectal Surgery at Charlotte Maxeke Johannesburg Academic Hospital (CMJAH) and Cluster Hospitals and Specialist Colorectal Surgeon at Busamed. She is a trained Laparoscopic Surgeon, Intervention Endoscopist. Founder and Public Relations of South African Society of women surgeons. She is first to perform HIPEC Surgery in Southern Africa. Currently Commissioning Minimal Invasive Surgery Guided Learning Pathway at Charlotte Maxeke for Fellows to advance Laparoscopic skills in Colorectal Surgery. PHD candidate. MBA graduate.

MEDChronicle TRANSFORMING LIVES

BY TRANSFORMING COLORECTAL HEALTHCARE

Reference: 1. Surgery for Colon Cancer. American Cancer Society website. https://www.cancer.org/cancer/colon-rectalcancer/ treating/colonsurgery.html. Updated February 21, 2018.

LAPAROSCOPIC APPROACH FOR COLORECTAL CANCERS

Treatment option for late stage colorectal cancer is removing cancerous area with surgery. And surgery can be performed as open or laparoscopically.1

Although every patient is not suitable for laparoscopic surgery, positive patient outcomes of laparoscopic surgery are really significant for patient’s quality of life.

MEDICAL CHRONICLE | April 2021 29

ETHICS

Court upholds the importance

of disclosure of medical records

Sandra Sithole, Webber Wentzel

In a recent case where a claimant for damages sought to prevent the disclosure of her medical records, the rules of court were found to override other legislation relating to confidentiality of personal information.

A

RECENT JUDGMENT, INVOLVING the assessment of damages for injury, has highlighted that the full disclosure of documents is necessary for the purposes of litigation, and other legislation is clearly not intended to conflict with the rules relating to discovery.

The judgment in the case of Divine Trading 205 (Pty) Limited & Another vs Gordon & Others deals with an application for the disclosure of medical records and the interplay between discovery of documents, the Uniform Rules of Court, and the circumstances under which a litigant can rely on lack of consent under the National Health Act, 2008, The Health Professions Act, 1974, and the Protection of Personal Information Act, 2013 for refusal to disclose medical records in a pending action.

Briefly, the facts are: • Ms Gordon sued the applicants, Divine Inspiration Trading 205 (Pty) Limited and the Alphen Farm Estate (Pty) Limited, for injuries she sustained in an accident when she visited their premises in October 2015.

• The merits of the claim were settled during September 2017. The settlement agreement provided that the applicants pay 70% of Ms Gordon's agreed or proven damages.

30 April 2021 | MEDICAL CHRONICLE

• As usually happens in such cases, following settlement of the merits, Ms Gordon amended her claim to increase the quantum from ZAR 500 000 to R7 million. The bulk of the claim related to her loss of earning capacity.

• In assessing the quantum, the applicants requested the medical records of Ms Gordon, including those from the second and third respondents, who were the general practitioner and psychiatrist who had treated Ms Gordon for certain medical conditions.

• The second and third respondents refused to disclose the medical records on the basis that they were precluded from doing so under the National Health Act, 2008. This Act prohibits the disclosure of a patient’s medical information without their consent (Ms Gordon had refused to provide the consent) unless "the court or any law requires that disclosure". The second and third respondents also relied on the Health Professions Act and their ethical duties which similarly limit the circumstances under which a healthcare practitioner may disclose a patient’s medical information.

• The applicants had sought to obtain the documents from the medical practitioners,

through a subpoena and a Rule 35(3) and (6) against Ms Gordon, on the basis that she had not discovered all documents relevant to her claim.

The Court found that the reference to "any law" in the National Health Act includes the rules of court. That means that health practitioners whose patients refused to consent to the disclosure of their medical records, cannot rely on this particular section of the National Health Act when they are served with a subpoena subject to questions of privilege. Ethical rules are also subject to those principles.

Arguing that the medical records are not relevant to her claim for loss of earning capacity and are not necessary to pursue the applicants' defence in the main action, Ms Gordon also sought to rely on the Protection of Personal Information Act (POPIA) in refusing to disclose her medical records. She did so on the basis that disclosing the medical records would unjustifiably trample upon her rights under POPIA, which provides that personal information (of which medical records is one) may only be processed if: • processing complies with an obligation imposed by the law on the responsible

party (a person who processes the personal information of others); • processing is necessary for pursuing the legitimate interests of the responsible party or of a third party to whom the information is supplied.

The Court found that Ms Gordon's treating medical practitioners were responsible parties as defined under POPIA and it was on them that obligations were "imposed by law" by virtue of the subpoenas served on them. Furthermore, POPIA provides that a data subject, in this case, Ms Gordon, may object to the processing of personal information unless legislation provides for such processing and once personal information has been collected, POPIA makes provision for the further processing for purposes of proceedings of any Court or tribunal proceedings.

On the facts, it was found that Ms Gordon had a history of anxiety, drug and alcohol use which may have had an impact on her career, without the injury.

The Court agreed with the applicants that her pre-morbid medical conditions could and probably would impact on her earning capacity and was therefore relevant to the assessment of her quantum.

ETHICS

The implications of prescribing and

administering ivermectin The COVID-19 pandemic has brought about worldwide economic, social and medical uncertainty

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OR DOCTORS, THIS uncertainty extends to whether new treatments will be beneficial to patients in protecting them from the coronavirus or not. They also worry about the medicolegal implications of clinical decisions they take in the face of rapidly evolving clinical knowledge and shifting regulations.

One of the drugs causing a dilemma for practitioners is ivermectin – the antiparasitic drug that has been punted in the media for its abilities to suppress coronavirus infections and its complications.

“Other than still undergoing clinical trials to understand potential benefits and risks at various doses, there are concerns about the availability of illegal products that are by-passing standard regulatory processes aimed at preventing distribution of sub-standard medications,” says Dr Bettina Taylor, head of clinical risk management at EthiQal, South Africa’s only insurer offering homegrown, occurrencebased medical malpractice cover to healthcare practitioners.

“Given punting of benefits of ivermectin in the media and the rapid clinical deterioration of some patients who have contracted COVID-19, doctors may nevertheless feel compelled to provide the medication, especially if pressurised by patients or their loved ones,” says Dr Taylor.

In this regard, a policyholder contacted EthiQal after receiving a request from a family member asking if they could administer ivermectin, of which they had personal stock, to a loved one who was in a medically induced coma.

In response to the doctor, EthiQal’s medicolegal team explores the legalities and clinical considerations:

LEGAL CONSIDERATIONS 1. Given that no ivermectin formulations for human use are registered in South Africa, the drug can only be administered legally in South Africa, if authorised on a named patient basis by the South African Health Products Regulatory Authority (SAHPRA), which is enabled to do so by Section 21 of the Medicines and Related Substances Control Act (Act no. 1010 of 1965). According to SAHPRA, license to use ivermectin will only be granted if the following requirements are met: 1.1. The relevant SAHPRA application form has been completed and submitted.

As part of this process, the doctor must also agree to provide feedback to SAHPRA on any adverse events encountered by any patient during treatment.

1.2. The source of ivermectin product to be used meets appropriate quality assurance standards. This includes that the product must have been supplied by a duly authorised importer that is compliant with the set requirements for authorisation, and where the product has a product validation report, a certificate of analysis, and outcomes of post-importation testing.

2. When access is required on an urgent basis, SAHPRA guidelines make provision for treatment to be initiated at the same time as an application for use for an individual patient. There is also a court order to this effect. There is no need to await approval by SAHPRA in these instances.

3. Licensed healthcare facilities or medical practitioners with a dispensing licence, may apply for authorisation to hold emergency stock of an ivermectin

product obtained from an authorised importer, to ensure availability of certified products when prescribed.

4. W here ivermectin is prescribed as part of SAHPRA’s compassionate use programme, the prescriber must ensure that the patient, or legal representative, has provided signed informed consent to the use of the drug.

CLINICAL CONSIDERATIONS 1. Unless a product is obtained from an authorised source that complies with SAHPRA standards, its quality is unknown. A recent study that analysed seven ivermectin formulations being sold in South Africa for human use, demonstrated that four of five formulations tested had at least one additional undeclared active pharmaceutical ingredient (API), while another product had seven. These active ingredients ranged from non-steroidal anti-inflammatories to anti-depressants, and from anti-platelet to antiemetic drugs amongst others. Other than not knowing the quantity of ivermectin in any product purchased illegally, there are safety concerns with regards to these unknown additional ingredients that can cause unexpected allergic reactions, drug interactions and side-effects specific to any undeclared ingredient.

2. Various local and international authorities like SAHPRA, FDA and the European Medicines Agency have highlighted that the benefit risk ratio of ivermectin in COVID-19 patients remains unknown.

Based on published studies, no recommendations in terms of whether treatment works and adverse events justify any potential benefit, can be made.

3. Given clinical equipoise with regards to use of ivermectin in COVID-19, as described in point 2. above, patients for whom treatment is considered should, wherever possible, be enrolled in relevant therapeutic trials.

Taking the above into consideration, the policyholder was advised that, unless ivermectin is attained via an acceptable source, and in accordance with the Section 21 processes, their actions would be deemed unlawful and unethical according to the HPCSA’s ethical and professional rules.

“Merely accepting the fact that the family is in possession of ivermectin, without anything else, could have onerous unintended effects for the doctor, including being charged for unprofessional conduct by the HPCSA, tried criminally or being civilly pursued,” advises Dr Hlombe Makuluma, EthiQal’s medicolegal advisor.

“The doctor could also lose his admission privileges at the hospital where he or she works, should the hospital become aware that they had unlawfully administered ivermectin to the patient, and breached hospital protocols in the process by not obtaining the drug through the hospital's pharmaceutical channels,” says Dr Makuluma. “The patient should be enrolled in a clinical trial if possible,” Dr Makuluma concludes.

Ivermectin has traditionally been used for river blindness and intestinal strongyloidiasis in humans in other parts of the world. It has also shown in vitro activity against SARS-Cov-2 and early signs of potential clinical benefit in patients infected with COVID-19. However, in South Africa only formulations for animal consumption are currently registered.

MEDICAL CHRONICLE | April 2021 31

WEBINAR REPORT

Raising the bar

in rheumatoid arthritis care Dr Kavita Makan, is a Rheumatologist and Specialist Physician at Chris Hani Baragwanath Academic Hospital and the University of the Witwatersrand. She is president of South African Rheumatism and Arthritis Association. She recently presented a webinar on treatment paradigms in rheumatoid arthritis (RA), hosted by Medical Chronicle and sponsored by Thermo Fisher Scientific.

Dr Kavitha Maharaj

Go to https://bit.ly/3bW3Jti to watch a replay of this webinar and earn your CPD point

T

HE FOLLOWING IS based on her presentation.

LEARNING OBJECTIVES • RA is more than a joint disease with multisystem complications and comorbidities • Early recognition and diagnosis is key to ensuring good outcomes • Early referral to a rheumatologist if suspect inflammatory arthritis • Early introduction of DMARDs reduces risk of damage and disability • Use a ‘Treat to Target’ approach to achieve remission or low disease activity • (LDA) • A multidisciplinary approach is imperative for optimal outcomes • New treatments have increased options for controlling disease – biosimilars and JAK-inhibitors.

RA is common, complex and changing.

It is the commonest inflammatory arthritis (0.5%–1% population prevalence). There is heterogeneity in its presentation, RA has a predilection for synovial joints but is a systemic disease. Cardiovascular morbidity and mortality in RA is similar to diabetes.

Early recognition and diagnosis is important. Joint damage occurs early and progresses rapidly. Seventy five per cent of early RA patients have radiographic erosions, >80% on MRI. Prevention of damage early preserves function. RA not a fixed phenotype but a continuum.

32 April 2021 | MEDICAL CHRONICLE

Radiographic changes in RA can be seen early on in the disease process.

Ultrasonography is a useful tool in early diagnosis. It identifies inflammation in early undifferentiated arthritis to assist with diagnosis. It also predicts radiographic progression – thus response to therapy and relapse risk after discontinuation of treatment.

Early referral to rheumatologist increases probability of Disease-modifying antirheumatic drugs (DMARD)-free remission in RA patients. Assessment at ≥12 weeks was associated with HR of 1.87 for not achieving DMARD-free remission and a 1.3 times higher rate of joint destruction over six years vs assessment in <12 weeks.

The updated classification criteria are helpful for diagnosing early RA. Two requirements are the patient must have at least one joint with definite clinical synovitis (swelling) and that synovitis is not better explained by another disease.

Early and aggressive use of DMARDs reduces risk of damage and disability. It does the following: • Allows better disease control • Creates possibility of drug-free remission - A major predictor of remission was to have very early RA, along with being on a DMARD within three months from disease onset - Early remission is associated with improved survival in patients with inflammatory polyarthritis – in terms of The Norfolk Arthritis Register • Prevents disability – better functional scores

• Slows x-ray progression - There are long-term benefits in preventing structural damage.

Longer symptom duration is associated with lower chance of DMARD-free sustained remission. Earlier clinical remission is associated with better survival. Early treatment prevents structural damage.

‘Treat to Target’ is a strategy to use, and includes: • Frequent assessments of patients (monthly) • Calculation of a composite disease activity score • Escalation of treatment if pre-defined target not met • Assess comorbidities and patient factors (reinforce education/compliance).

The target for every patient should be remission or low disease activity.

Conventional DMARDs used early can control disease if used appropriately.

Methotrexate is the anchor drug.

Leflunomide in combination with methotrexate has good safety and efficacy profile in refractory RA and acceptable in resource-poor settings. Monitoring for druginduced side effects and toxicity is essential at every visit.

A multidisciplinary approach is essential to successful management of RA. Patient education about the disease, treatment and outcomes, comorbidities, pain, disability, work and social participation is important. A multidisciplinary team might include: • Occupational therapy

• Physiotherapy • Podiatry • Lifestyle modifications (RA and comorbidities) • Weight control • Dental care.

Exercise should be at a moderatehigh intensity, aerobic and strength training, as long as there is no increase pain or disease activity. A Mediterranean diet high in omega-3 fatty acids, vegetables and antioxidants is recommended. Smoking cessation is important in these patients.

TAKE-HOME MESSAGES Consider RA the disease, complications (drugs and condition) and comorbidities.

Remember the three’s of inflammatory arthritis, and refer early to a rheumatologist.

Stiffness – early morning joint stiffness lasting more than 30 minutes. Swelling – persistent swelling of one joint or more, especially hand joints. Squeezing – squeezing the joints is painful in inflammatory arthritis.

Early diagnosis and treatment with DMARDs improves outcomes and survival.

Tight control using a ‘Treat to Target’ approach is crucial to achieving the ultimate goal of sustained drug-free remission or low disease activity. Treatment should be individualised, with shared decision making between patient and doctor using a multidisciplinary approach. Biosimilars and Janus kinase inhibitors (JAK-inhibitors) have entered the SA space and provide greater options for patients with RA.

WEBINAR REPORT

Covid-19 in rhinology and allergy Prof Joaquim Mullol, director of the Rhinology Unit & Smell Clinic, ENT Department, Hospital Clínic Barcelona, recently shared his extensive knowledge at a webinar held by Medical Chronicle and sponsored by iNova Pharmaceuticals. The following article is based on his presentation titled: Covid-19 in Rhinology and Allergy – impact on smell and type 2 inflammation.

T

HE LOSS OF smell and taste is common (60%-70% of cases) in SARS-CoV-2-infected patients.

One in five patients with Covid-19, loss of smell and taste can present as sudden, severe, and isolated from other nasal or systemic symptoms. Loss of smell is more frequently diagnosed (70%-80%) when measured with smell tests than using questionnaires (45%-50%).

For a proper and safe diagnosis, the use of individualised olfactory and gustatory tests or a visual analogue scale (VAS, 0-10cm horizontal line), in person or by telemedicine, is recommended in patients with Covid-19. A potential protective effect of developing Covid-19 is currently being hypothesised in patients with respiratory type 2 inflammation (allergic rhinitis, asthma, chronic rhinosinusitis with nasal polyps), potentially due to eosinophil tissue infiltration. During the outbreak of Covid-19, while awaiting immunisation by vaccination of the general population, the best treatment is prevention of infection: Frequent hand washing, use of facial masks, social distancing, and home isolation when required.

In patients with sudden, severe and isolated loss of smell or taste, immediate home isolation is recommended when waiting for a SARS-CoV-2 diagnostic test.

In the absence of effective drugs, olfactory training is a valid, effective, and recommended therapy to recover the sense of smell in Covid-19 patients that should be started as soon as possible.

However, patients with respiratory type 2 diseases, the regular use of first-line therapeutic drugs (anti-H1, corticosteroids, allergen immunotherapy or biologicals) should not be discontinued.

CRITICISM OF METHODOLOGY Most studies provide only qualitative (surveys and questionnaires) but no quantitative (smell test, VAS) data on the loss of smell or taste. There is also no distinction between flavour (smell + taste) and real taste.

CRITICISM OF RESULTS There is a high variability in the frequency of loss of smell (from 5% to 85%) and high variability in the frequency of loss of taste (from 5% to 88%). Data on loss of smell and taste seems to confirm ‘flavour = taste’.

FINAL CONCLUSIONS Most Covid-19 patients (>60%) present loss of smell and/or loss/ distortion of taste as additional symptoms in Covid-19.

Some Covid-19 patients (15-20%) present a sudden-severe-isolated loss of smell/taste. Most patients (>90%) recover the sense of smell/taste within the first month. Olfactory training is recommended.

Recommendations in Covid-19 outbreak 1. More than 90% of patients improve within the first month 2. Intranasal corticosteroids can be recommended at regular doses in concomitant upper airway disease (allergic rhinitis, CRS, CRSwNP) but are not recommended in sudden, severe, and

isolated loss of smell 3. Olfactory training could be started after one month or immediately.

2. Receptor blockers 3. Vaccination (T-cells) 4. Mechanical filtration.

The trinity of Covid-19 is: Immunity – Inflammation – Intervention Prevention: 1. Vaccination (Ab)

To watch a replay of this presentation and earn a CPD point, go to: https://bit. ly/3dmumbA

FREE content for CPD Medical Chronicle readers

Sign up for our CPD, It’s so easy you’ll have more time for other things...

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IT’S AS EASY AS: • Visit www.medicalacademic.co.za • Click on CPD Portal • Fill out form

MEDICAL CHRONICLE | April 2021 33

OPINION

When does long Covid end?

As the Covid-19 Pandemic progresses, some patients are experiencing prolonged multi-organ symptoms and complications beyond the initial period of acute infection and illness.

T

HE LIST OF new and persisting symptoms reported by patients is extensive and includes: Chronic cough, shortness of breath, chest tightness, cognitive dysfunction, and extreme fatigue. This has been termed ‘Long Covid’ or ‘Post Covid-19 Syndrome’.

The Syndrome is defined as a collection of symptoms lasting more than 28 days.

The implications and consequences of such ongoing clinical manifestations are growing and is a health concern.

Work is being done to try and understand why following Covid-19 infection, the impact varies from full recovery to severe persistent debilitating symptoms affecting multiple organs and mental health.

Research suggests that one in five people who test positive for Covid-19 have symptoms for five weeks or longer. In the UK this equates to 186 000 individuals with symptoms persisting for five to 12 weeks.

Med RX IV preprint survey done on 3 700 self-described Covid-19 ‘Long Haulers’ in 56 countries showed that nearly 50% could not return to full-time work six months after unexpectedly developing prolonged symptoms of Covid-19.

The second study emphasised the course and severity of more than 200 symptoms over time, including those

34 April 2021 | MEDICAL CHRONICLE

affecting the heart, lungs, gastro-intestinal system, muscles and joints. There was also an in-depth look at neurological and neuropsychiatric symptoms.

In a survey of 3 762 individuals in USA - More than 50% never sought hospital care - 8% were admitted to hospital for Covid-19 - 2 464 reported Covid-19 symptoms lasting six months.

Among the most common symptoms were fatigue, worsening of symptoms after physical or mental activity, shortness of breath, trouble sleeping and difficulty thinking clearly. The majority, (80%) said that they coped with some form of cognitive dysfunction or memory loss that to varying degrees affected their everyday lives. This includes the ability to make decisions, have conversations, follow instructions and drive.

Those who had Covid-19 symptoms for more than six months reported contending with 14 symptoms on average.

Many reported relapses of symptoms seemingly triggered by exercise, mental activity or just everyday stress.

More than 50% of respondents said that they had to reduce their hours at work due to the severity of the symptoms.

Another 22% were not working at all due to their Long Covid. Studies show that even

those who were not hospitalised for severe Covid-19, the prolonged symptoms are having a major impact on lives and livelihoods.

Six months after onset of illness, more than 75% of people hospitalised with Covid-19 in Wuhan between January and May 2020 continued to report at least one symptom: fatigue, muscle weakness, sleep difficulties, anxiety and depression.

More than 50% had significant persistent abnormalities, which were more common in those who had been more severely ill. A Study done at Kings College in the UK, found that one in every 20 people experienced long term symptoms. Work done in the NHS in Wales reported one in 10 have symptoms after three weeks and some may suffer for months.

Journal of American Medical Association – Team of Researchers from Italy reported nearly nine out of 10 patients (87%) discharged from hospital in Rome were still experiencing at least one symptom, 60 days after onset.

Why do people suffer longer?

There are a number of theories. Some theories from Kings College in the UK: - Severity of the initial illness - Prolonged and inappropriate immune

Prof Morgan Chetty, visiting Prof: Health Sciences, DUT chairman, IPAF, CEO: KZNDHC

response after the infection has been cleared -P atients being biologically predisposed to such a response.

Other theories proposed why some people’s recovery is prolonged: - Relapse or re-infection - Inflammatory or other immune reactions - Deconditioning -M ental disorders like Post Traumatic Stress (PTS).

SOME EXPLANATIONS Interferon alpha, when given to people as a treatment for Hepatitis C, generated a ‘flulike illness’ in many patients and post viral fatigue in a few.

Researchers have studied this artificial infection response as a model of chronic fatigue. They found the baseline levels of two molecules in the body that promote inflammation: Interleuken 6 and Interleuken 10, predicts people’s subsequent development of chronic fatigue.

The theory of ‘Super Antigen’ in the spike of the coronavirus, which causes multiple inflammatory syndrome in children is being proposed to cause multiple inflammatory syndrome in adults that may results in the presentation of Long Covid.

PLACEBO

SABS issues new standard

for hand sanitisers

MEDChronicle © Copyright Medical Chronicle 2020

EDITORIAL EDITOR: Claire Rush McMillan Claire.Rush@newmedia.co.za NEWS WRITER: Nicky Belseck Nicky.Belseck@newmedia.co.za SUB-EDITOR: Gill Abrahams

The SABS has issued a new standard for hand sanitisers, which manufacturers of these products and employers distributing them in the workplace should comply with.

EDITORIAL CONTRIBUTORS Dr Sian Hartshorne, Dr Marshinee Naidoo, Sandra Sithole, Prof Morgan Chetty.

LAYOUT & DESIGN: Naresh Budraj

Kate Collier, Shane Johnson and Matthew Ilsley of Webber Wentzel

A

LMOST A YEAR after South Africa recorded its first Covid-19 case, the use of hand sanitisers has become commonplace, including at workplaces. The South African Bureau of Standards (SABS) has issued a new standard (amended SANS 490) for hand sanitisers. We summarise the key information from the new standard for employers below.

the labelling of hand sanitiser products must contain the following minimum information:

DISTRIBUTION & SUBSCRIPTIONS Felicity Garbers Email: felicity.garbers@newmedia.co.za Update your details here: www.medicalacademic.co.za

The registration number and full address of the manufacturer/producer Alcohol percentage

PUBLISHING TEAM GENERAL MANAGER: Dev Naidoo PUBLISHING MANAGER: Johann Gerber Email: Johann.Gerber@newmedia.co.za PRODUCTION MANAGER: Angela Silver ART DIRECTOR: David Kyslinger

"Flammable" warning

New minimum alcohol content thresholds Hand sanitisers with no 'active' ingredients must have a minimum 70% alcohol content. Hand sanitisers with 'active' ingredients must have a minimum of 60% alcohol content.

'Active' ingredients are biologically active ingredients such as benzalkonium chloride.

Prohibited ingredients The following hand sanitiser ingredients have been cited as having extraneous toxicity levels, posing a danger to users when absorbed through the skin: Acetone Methanol Methylated sprits These are now considered to be prohibited ingredients and hand sanitisers may no longer contain them.

Packaging and labelling requirements SANS 490 requires hand sanitisers to be packaged and labelled according to set standards. The amended SANS 490 adds further requirements for packaging and labelling. Hand sanitiser packaging may not contain cork closure lids and

ADVERTISING ADVERTISING EXECUTIVES Anel du Plooy - Tel: 082 786 9517 Anel.duPlooy@newmedia.co.za Cindy Riederer - Tel: 082 492 0229 Cindy.Riederer@newmedia.co.za

"Do not ingest" warning

"Store below certain temperature" warning

CONTACT Johannesburg Office: Ground floor, Media Park, 69 Kingsway Avenue, Auckland Park 2092 Postal Address: PO Box 784698, Sandton, Johannesburg 2146 Tel: +27 (0)11 877 6111 Fax: +27 (0)11 713 9024

Whether the sanitiser is a gel or liquid Volume or mass of the liquid or gel The ingredients, and specifically the type of alcohol

COVER PRICE Medical Chronicle per issue R60.00 VAT Incl.

Expiry date and batch number

Published by New Media, a division of Media24 (Pty) Ltd

Instructions for use

Printed by

SABS-approved mark, if the manufacturer is a SABS-approved manufacturer or brand

, a division of Novus Holdings

MANAGEMENT TEAM CEO : Aileen Lamb COMMERCIAL DIRECTOR: Maria Tiganis BRAND STRATEGY DIRECTOR: Andrew Nunneley CHIEF FINANCIAL OFFICER: Venette Malone CEO: MEDIA24: Ishmet Davidson

The amended SANS 490 must be followed not only by hand sanitiser manufacturers but also employers who distribute hand sanitisers in the workplace. If hand sanitisers do not comply with the amended SANS 490, employers should not distribute them in the workplace.

By distributing hand sanitisers that comply with the amended SANS 490, employers will ensure that the health and safety of their employees and anyone else who may enter the workplace is sufficiently safeguarded.

HEAD OFFICE New Media, a division of Media24 (Pty) Ltd 8th floor, Media24 Centre, 40 Heerengracht Cape Town, 8001 www.newmedia.co.za Unless previously agreed in writing, Medical Chronicle owns all rights to all contributions, whether image or text.

SOURCES: Shutterstock, supplied images, editorial staff.

While precautions have been taken to ensure the accuracy of its contents and information given to readers, neither the editor, publisher, or its agents can accept responsibility for damages or injury which arise therefrom. All rights reserved. © Medical Chronicle. No part of this publication be reproduced, stored in a retrieval system or transmitted in any form or by any means, photocopying, electronic, mechanical or otherwise without the prior written permission of the copyright owners. Attention African readers: Please note that some products might not be available in your region and product names could vary. Please contact your local distributors, agents or pharmaceutical companies concerned for any discrepancies.

MEDICAL CHRONICLE | April 2021 35