Specialist Forum September 2024

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Spring into heart health action

Insights from the forefront of stroke care: Key highlights from the House of Stroke Symposium

Global heart woes: A growing

rosuvastatin dosages enhance dyslipidaemia treatment

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Eyeing better health in diabetes: How PG-HPG nanoemulsion artificial tears tackle dry eye

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Exploring benign prostatic hyperplasia treatments: Mono- vs combo therapy 25

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Early detection saves lives: The critical role of screening and testing for hepatitis C

Online CPD: The role on novel hormone therapy in mCRPCa

Link between ADHD and ODD

Clear skin solutions, effective acne treatments and strategies

Managing atopic dermatitis comorbidities

38 Advanced treatment options in psoriasis

Selecting treatment for PCa patients based on affordability vs efficacy

From earaches to sneezes: Common

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Spring into heart health action

September not only heralds the start of Spring in South Africa, but also Heart Awareness Month, and World Health Day on 29 September. The theme of this year’s World Health Day is Use Heart for Action.

Cardiovascular disease (CVD) remains a leading cause of morbidity and mortality worldwide. It includes a range of conditions affecting the heart and blood vessels, including coronary artery disease, heart failure, and stroke. The global prevalence of CVD is influenced by various factors, including lifestyle, genetics, and socioeconomic conditions.

According to the World Health Organization (WHO), CVD is responsible for ~17.9 million deaths annually, accounting for 31% of all global deaths. Of these deaths, 85% are due to heart attack and stroke.

The burden of CVD is not uniformly distributed across the globe. It varies significantly between high-income and lowand middle-income countries. In high-income countries, the prevalence of CVD has been relatively stable or even declining in recent years, thanks to improved healthcare systems, better management of risk factors, and advancements in medical technology.

For instance, the United States has seen a decline in CVD mortality rates due to effective public health campaigns, widespread use of medications like statins, and improved emergency care for heart attacks and strokes.

Conversely, low- and middle-income countries are experiencing a surge in CVD prevalence. These regions account for over 75% of CVD deaths globally. The rise in CVD in these countries is attributed to urbanisation, changes in dietary habits, increased tobacco use, and reduced physical activity. Additionally, limited access to healthcare services and preventive measures exacerbates the situation.

Several modifiable and non-modifiable risk factors contribute to the global prevalence of CVD. Modifiable risk factors include hypertension, high cholesterol, diabetes, smoking, obesity, and physical inactivity. Some of these risk factors are discussed in this issue.

Non-modifiable risk factors encompass age, gender, and family history of CVD. Addressing these risk factors through lifestyle changes and medical interventions is crucial in reducing the global burden of CVD.

Preventive measures play a vital role in combating CVD. Public health initiatives focusing on smoking cessation, promoting healthy diets, encouraging physical activity, and controlling hypertension and diabetes are essential. Also, early detection and management of CVD through regular health check-ups and medications can significantly reduce the risk of severe outcomes.

References

World Health Organization. Cardiovascular diseases (CVDs). Available from: https://www.who.int/news-room/fact-sheets/detail/ cardiovascular-diseases-(cvds)

Roth GA, Johnson C, Abajobir A, et al Global, Regional, and National Burden of Cardiovascular Diseases for 10 Causes, 1990 to 2015. J Am Coll Cardiol, 2017.

Benjamin EJ, Muntner P, Alonso A, et al Heart Disease and Stroke Statistics—2019

Update: A Report from the American Heart Association. Circulation, 2019.

Hope you enjoy the read!

Regards René Bosman

Insights from the forefront of stroke care:

Key highlights from the House of Stroke Symposium

Boehringer Ingelheim recently hosted a House of Stroke Symposium, featuring presentations from some of the country’s leading experts. The symposium explored various aspects of stroke management, including the urgent need to treat stroke as an emergency, the immediate diagnosis and prioritisation of critical patients, the ongoing debate between thrombolysis and thrombectomy, the complexities of atypical stroke presentations, navigating intracranial haemorrhage and addressing ethical dilemmas in stroke care. This issue will focus on the first three presentations, while the October and November issues will highlight the remaining topics.

Is stroke an emergency?

Dr Louis Kroon, neurologist, Steve Biko Academic Hospital and a lecturer at the University of Pretoria

Stroke is a critical medical emergency that requires immediate intervention, particularly because the timing of treatment significantly influences patient outcomes. Historically, the administration of tissue plasminogen activator (TPA) was limited to a six-hour window.

However, landmark trials expanded this treatment window to 24 hours, which led to updated guidelines that now inform current stroke management protocols.

The importance of early treatment is underscored when examining stroke outcomes within the initial threehour window. During this period, TPA administration is most effective, showing considerable benefits, especially in patients without large vessel occlusions (LVOs). However, when LVOs are present, the effectiveness of TPA alone diminishes, necessitating additional interventions like thrombectomy.

When TPA is combined with thrombectomy, the results are compelling, with one in four patients experiencing significantly improved outcomes. This combination makes it one of the most effective treatments currently available in medicine.

The necessity of such timely interventions is amplified by the global burden of stroke,

which remains one of the leading causes of mortality worldwide. In low- and middleincome countries, stroke incidence has doubled from the 1990s to 2016, while it has declined by 42% in higher-income countries during the same period.

Notably, Africa experiences nearly a threefold higher stroke incidence and prevalence compared to Western Europe and the United States, translating to one stroke every three seconds globally, with potentially one in three people in South Africa expected to suffer a stroke.

The introduction of these new treatment guidelines has transformed stroke care, particularly in units like the one at Steve Biko Academic Hospital. From December 2020 to July 2024, the hospital’s stroke unit evaluated >4100 patients, achieving high sensitivity in identifying strokes, albeit at the cost of some specificity, leading to a number of stroke mimics.

Nevertheless, prioritising sensitivity is crucial, as some strokes, particularly those presenting with atypical symptoms or mild deficits, can be easily missed, which would delay critical treatment.

One of the most significant challenges in stroke management is overcoming the reluctance to urgently image patients due to concerns over contrast-related kidney injuries. However, a meta-analysis of 14 studies emphasised that brain angioperfusion studies are not associated with a significant increase in acute kidney

injury risk, even in patients with chronic kidney disease.

Another challenge is the misconception surrounding iodine allergies, often believed to be related to contrast media. The truth is that iodine, a normal trace element in the body, cannot be an allergen. Rather, the allergenic reactions are caused by parvalbumin, a protein found in seafood. Furthermore, the concern over radiation exposure during CT perfusion imaging has been mitigated by advancements in technology, allowing for effective scans with minimal radiation exposure, comparable to background radiation levels in certain geographic regions.

Immediate diagnosis for all patients - prioritising the critical Dr Ebrahim Kader, interventional and diagnostic neuroradiologist at Morton and Partners Radiologists and past-president Radiological Society of South Africa

Stroke, often described as a ‘brain attack’, represents a critical neurological emergency where timely intervention is essential to minimise damage and improve outcomes. Stroke occurs when there is an interruption of blood supply to the brain, either due to a blockage (ischaemic stroke) or a bleed (haemorrhagic stroke). The brain’s dependence on glucose and oxygen makes it highly vulnerable to disruptions in blood flow.

Under normal conditions, the brain consumes about 40% of the available oxygen and maintains a delicate balance of blood flow through various compensatory mechanisms. However, when blood flow drops to around 30%-40% of normal levels, symptomatic ischaemia ensues, and cell death becomes a risk when blood flow falls below 20%.

In cases of ischaemic stroke, the affected brain tissue undergoes rapid changes. Initially, there is a failure of the sodiumpotassium pump due to insufficient oxygen and adenosine triphosphate, leading to cellular swelling and loss of brain structure differentiation. The critical threshold for irreversible damage is reached when cerebral blood flow (CBF) falls to 20% of normal levels.

Imaging is pivotal in diagnosing and managing stroke. The primary goal of initial imaging is not only to confirm the diagnosis of stroke but also to exclude contraindications to treatments like thrombolysis and identify alternative diagnoses. Imaging modalities used include: _ The first-line imaging tool for stroke, non-contrast CT (NCCT) is quick,

cost-effective, and readily available. It helps to exclude intracranial haemorrhage and other structural abnormalities. However, it has limited sensitivity for detecting acute ischemia.

_ CT angiography is used to visualise LVOs and can identify conditions such as aneurysms or dissections.

_ CT venography is effective to assess collateral circulation and is useful for planning interventional procedures. It is particularly effective in detecting thrombus within vessels and understanding collateral circulation dynamics.

_ CT perfusion provides a quantitative assessment of cerebral blood flow, blood volume, and mean transit time. It helps delineate the extent of ischaemic damage and differentiate between salvageable brain tissue (penumbra) and irreversibly damaged tissue (core). Key parameters include cerebral blood volume, CBF, and time to peak (TTP), with T-max indicating critical hypoperfusion.

_ Magnetic resonance imaging offers detailed images and can reveal acute ischemic changes earlier than CT.

_ MR perfusion assesses brain tissue viability and helps in planning thrombolysis or thrombectomy. It distinguishes between core infarct and penumbra using parameters such as diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR). DWI indicates areas of restricted diffusion, while FLAIR highlights areas with prolonged signal changes. In stroke management, imaging results guide treatment decisions, such as thrombolysis or thrombectomy. Accurate and timely imaging can significantly impact patient outcomes by identifying patients with large penumbra who may benefit from mechanical thrombectomy.

Advanced imaging techniques, although more resourceintensive, provide critical insights into the extent of ischemic damage and the potential for tissue salvage.

The choice of imaging protocol should be consistent and tailored to each institution’s capabilities and patient population. A standardised imaging protocol ensures reliable and reproducible results, minimising the risk of missed diagnoses or suboptimal treatment decisions. For example, protocols should address the timing of imaging and the interpretation of results to align with current guidelines and best practices.

The couch of controversy: Thrombolysis vs thrombectomy

Dr Wiebren Duim, neurologist based at Groenkloof Life Hospital in Pretoria

The pivotal National Institute of Neurological Disorders and Stroke Trial, published in 1995, demonstrated the efficacy of TPA in improving stroke outcomes.

The concept of ‘time is brain’ highlights the urgency of rapid intervention. Every minute counts, and delays in treatment can lead to worse outcomes. To emphasise the importance of swift action, consider the Ferrari Formula 1 pit stop analogy, said Dr Duim.

Just as pit stops are meticulously timed and executed, stroke treatment should be equally precise and prompt. This requires a well-coordinated effort among healthcare providers, from initial assessment to treatment.

Evidence from various trials and registries shows that timely TPA administration not only improves survival rates but also enhances functional recovery.

The 2021 European Stroke Organization guidelines strongly recommend intravenous thrombolysis within four and a half hours of symptom onset. Data from meta-analyses confirm that TPA offers a 46% improvement in achieving excellent outcomes. As we move forward, let us remember the impact of effective

stroke care on patients’ lives. Investing in training, infrastructure, and rapid response systems is not just an option - it is a necessity for advancing stroke care in South Africa, stressed Dr Duim.

Key messages

1

Stroke should be treated as a critical emergency, as immediate intervention is crucial. The faster a stroke is identified and treated, the better the chances of minimising brain damage and improving patient outcomes. Delays in treatment can lead to irreversible damage and significantly worse outcomes.

2

3

Accurate and timely imaging is essential in stroke management. Imaging not only confirms the diagnosis of stroke but also guides treatment decisions, helping to identify patients who can benefit from interventions like thrombolysis or thrombectomy. Advanced imaging techniques enable the precise assessment of brain tissue viability, which is critical in selecting the appropriate treatment.

Thrombolysis is a highly effective treatment when administered within the first few hours of symptom onset. It can significantly improve outcomes by dissolving the blood clots that block blood flow to the brain, thereby restoring circulation and reducing the extent of brain damage. When used promptly, thrombolysis can enhance the chances of a full recovery and minimise long-term disability, making it a crucial intervention in the early stages of stroke. SF

CARDIOLOGY | Cardiovascular diseases

Global heart woes: A growing crisis

Cardiovascular diseases (CVDs) are the leading global cause of death, responsible for 20.5 million deaths in 2021, accounting for ~33% of all global fatalities. Once considered diseases of affluence, >75% of CVDrelated deaths now occur in low- and middleincome countries (LMICs).

CVD jumped from the sixth to the second leading cause of death in sub-Saharan Africa between 1990 and 2019. The burden of CVDs in sub-Saharan Africa is more severe and affects younger, working-age individuals. 2,3

The higher mortality among younger people in LMICs is likely due to inadequate prevention and management, as CVD prevention is often not prioritised, and effective treatments are less accessible, according to Abdelatif et al 3

Globally, ischaemic heart disease is the leading cause of early death. However, in Africa, stroke - particularly hypertensive stroke - has historically been the primary contributor to CVD mortality. In subSaharan Africa, hypertension, rheumatic heart disease, and cardiomyopathies (eg endomyocardial fibrosis) are the main causes of heart failure. 2

What is driving the CVD epidemic?

Cardiometabolic risk factors are highly prevalent across Africa, with 10-year risk scores for men ranging from 12.5% to 15.3%. Hypertension, diabetes, and obesity are the most common risk factors, with central obesity linked to a higher risk of CVD and mortality than high BMI alone. 2

Recently, Kazi et al conducted a systematic review of 492 observational studies to determine whether climate change–related environmental stressors, such as extreme temperatures and hurricanes, were linked to higher morbidity and mortality rates from CVDs. 4

Of the 492 studies included, 182 investigated extreme temperatures, 210 assessed ground-level ozone, 45 evaluated wildfire smoke, and 63 looked at extreme weather events like hurricanes, dust storms, and droughts. 4

They found that exposure to extreme temperatures was linked to higher CV morbidity and mortality, with the severity depending on the temperature and exposure duration. Ground-level ozone increased the risk associated with extreme heat, and extreme weather events, such as hurricanes, were linked to long-term CV risks. 4

Wildfire smoke exposure showed inconsistent results, with some studies reporting an increase in CV events like outof-hospital cardiac arrests and ischaemic heart disease hospitalisations, while others found no significant association. 4

Vulnerable populations, such as older adults, racial and ethnic minorities,

and low-income communities, were disproportionately affected by these environmental stressors. 4

The authors concluded that as climate change increases the frequency and intensity of environmental stressors, the associated CV risks are expected to increase. Urgent efforts are needed to address the CV risks linked to climate change, particularly in vulnerable populations, they stressed.

Conclusion

CVDs continue to be the leading cause of global mortality, with an increasing burden in LMICs. The high prevalence of cardiometabolic risk factors, combined with inadequate prevention and treatment, contributes to higher mortality rates in younger, working-age individuals. Ischaemic heart disease and stroke are the major drivers of CVD mortality, while emerging threats, such as climate change-related environmental stressors, further elevate the risks. Addressing these challenges through improved prevention, management, and climate action is essential, especially for vulnerable populations.

References are available on request. SF

New rosuvastatin dosages enhance dyslipidaemia treatment

Dyslipidaemia is a significant risk factor for cardiovascular diseases (CVD). CVD contribute to >2 million deaths and ~30 million disabilities globally each year. Community-based surveys in South Africa has shown an extremely high prevalence of dislipidaemia (up to 93.5%) among the general population.1

Dyslipidaemia is defined as abnormal levels of one or more of the following in the blood: Total cholesterol (TC), lowdensity lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG).1

While the precise causes of dislipidaemia are not fully understood, research shows that it can be caused by metabolic disorders such as obesity, hypertension, and diabetes.1

The cornerstone of dyslipidaemia treatment is lifestyle management, which includes dietary changes, increased physical activity, and weight loss if necessary. Alongside these lifestyle adjustments, dyslipidaemia can also be treated with pharmacotherapy.1

The updated consensus guidelines for managing dyslipidaemia in South Africa (2018) recommend statin therapy for all patients at risk for CVD, including those with diabetes and familial hypercholesterolaemia.1

How effective are statins in reducing cholesterol levels?

Statins are 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors that

effectively lower total and LDL-C levels. Large randomised controlled trials have consistently shown that reducing LDL-C – especially with statins – significantly decreases the risk of CV events and mortality.2

The reduction in CV events resulting from the use of statins is directly proportional to the decrease in LDL-C levels. The Cholesterol Treatment Trialists’ Collaborators’ metaanalysis demonstrated that a 1mmol/L decrease in LDL-C correlates with a 20% reduction in CV risk. This benefit was also supported by the Management of Elevated Cholesterol in the Primary Prevention Group of Adult Japanese study, which showed a 33% reduction in CV events.2

Are all statins equally effective?

The Study to Evaluate the Long-term Lipid-lowering Efficacy and Safety of Rosuvastatin study demonstrated that rosuvastatin is the most potent statin. After six weeks of treatment, rosuvastatin at doses of 10mg-40mg reduced LDL-C levels by 46%-55%. 3

In comparison, atorvastatin 10mg-80mg reduced LDL-C by 37%-51%, simvastatin

10mg-40mg by 28%-39%, and pravastatin 10mg-40mg by 20%-30%. 3

Rosuvastatin also significantly increased HDL-C by 8%-10%, compared to 2%-6% with atorvastatin, 5% with simvastatin, and 3%-6% with pravastatin. Additionally, rosuvastatin decreased TG levels by 20%-26%, whereas atorvastatin reduced triglycerides by 20%-28%, simvastatin by 12%-15%, and pravastatin by 8%-13%. 3

These findings were corroborated by the Vascular Outcomes in Young Adults with Elevated Risk study, which pooled data from 32 258 individual patients across various trials comparing rosuvastatin with atorvastatin or simvastatin. Furthermore, a meta-analysis, which included 50 studies and 51 956 patients, confirmed rosuvastatin’s superior efficacy in reducing LDL-C levels compared to other statins. 3

In South Africa, rosuvastatin is indicated for adult patients at increased risk of atherosclerotic CVD (ASCVD), who present with risk factors such as elevated highsensitivity C-reactive protein (hsCRP) levels, advanced age, hypertension, low HDL-C, smoking, or a family history of premature

CARDIOLOGY | Dislipidaemia

coronary heart disease. In these patients, rosuvastatin reduce the risk of non-fatal stroke, non-fatal myocardial infarction (MI), and the need for arterial revascularisation. 4

For individuals living with hypercholesterolaemia, rosuvastatin is indicated for managing primary hypercholesterolaemia, mixed dyslipidaemia, and isolated hypertriglyceridaemia, including conditions classified under Fredrickson Type IIa, IIb, and IV, as well as heterozygous familial and non-familial hypercholesterolaemia.4

In paediatric patients aged 10- to 17-years living with heterozygous familial hypercholesterolaemia, rosuvastatin is indicated for lowering TC, LDL-C, and Apo B levels. 4

Role of rosuvastatin in primary and secondary prevention of CVD

Primary prevention of CVD

The Justification for the Use of Statins in Primary Prevention: An Intervention Trial

Evaluating Rosuvastatin trial evaluated rosuvastatin’s impact on a group of apparently healthy participants (n=17 802) with normal LDL-C but high hsCRP. 2 Results indicated that rosuvastatin reduced median LDL-C by 50%, hsCRP by 37%, and TG by 17%, leading to a 44% reduction in major CV events, including MI and stroke. Importantly, rosuvastatin’s benefits were consistent across various demographics and risk levels. 2

Further analyses revealed that rosuvastatin provided incremental benefits in intermediate-risk patients compared to those with low or high risk. When combined with low hsCRP levels, rosuvastatin’s impact on reducing residual CV risk was particularly notable. 2

Secondary prevention of CVD

A Study to Evaluate the Effect of Rosuvastatin on Intravascular Ultrasoundderived Coronary Atheroma Burden found that rosuvastatin 40mg led to significant reductions in LDL-C and atheroma volume, contributing to plaque regression in 78% of participants. 2

In acute coronary syndrome, intensive statin therapy is recommended. Studies including

Comparison of the Effects Noted in The ApoB ratio Using Rosuvastatin or Atorvastatin in Patients with Acute Coronary Syndrome and the Secondary Prevention of Acute Coronary Events – Reduction of Cholesterol to Key European Targets Trial highlighted the efficacy of LDL-C lowering and potential for achieving optimal treatment goals in patients diagnosed with acute coronary syndrome.2

Despite the efficacy of statins, why do patients fail to meet targets?

According to international guidelines, patients do not meet targets because statins are often prescribed at the lowest dose and not adequately up-titrated to achieve treatment goals. 5

Most statins, except for rosuvastatin, which is available in dosage strengths from 5mg to 40mg, are available in four dosage strengths – mostly 10mg, 20mg, 40mg and 80mg. 6

Most patients are prescribed the two lowest doses, while the highest doses are rarely used. Furthermore, healthcare professionals tend to maintain low initial doses and seldom opt to prescribe higher doses, which highlights the need for intermediate options. 5,6

Another challenge is that treatment adherence over the long term is poor, with >33% of patients stopping their statin treatment within a year. As a result, these patients are not getting the maximum benefit of this preventive strategy. They remain at an increased risk for the development and/or progression of CVD despite receiving treatment. 5

To address these gaps, Pharma Dynamics recently introduced generic rosuvastatin at 15mg and 30mg dosages. The wide range of dosage strengths of rosuvastatin allows treatment to be adjusted to the requirements of individual patients and increases the percentage of patients that reach their target lipid levels. 5,6

Are the new dosages safe and effective?

According to Brus and Barbič-Žagar, <3% of participants in their study experienced side effects. Furthermore,

post-authorisation studies involving ~7000 participants demonstrated good tolerability and confirmed the expected efficacy of rosuvastatin, including the new 15mg and 30mg dosage strengths. 6

The efficacy and safety of 15mg and 30mg rosuvastatin were shown in two sub-analyses of the ROSUvastatin dose titration in the treatment of PATients with Hyperlipidemia trial. The first sub-analysis evaluated the efficacy and safety of higher doses of rosuvastatin (15mg and 30mg), while the second analysed the efficacy and safety of rosuvastatin 15mg compared to 10mg.7,8

In the first sub-analysis, LDL-C goal achievement with rosuvastatin 10mg and 30mg was evaluated across different risk categories (moderate, high, very-high). Those at moderate, high, and very-high CV risk achieved LDL-C goals with success rates of 83.4%, 66.7%, and 33.0%, respectively. Among very-high risk patients, 55.7% reached the target LDL-C goal of <1.8mmol/l with ≥50% reduction from baseline. Moderate and high-risk patients generally met their LDL-C targets, whereas very-high risk patients required higher doses for optimal results.7 In the second sub-analysis, participants were randomised to either a standard titration arm (10mg, 20mg, 40mg) or an alternative titration arm (15mg, 30mg, 40mg). Lipid levels and safety parameters were measured at baseline and during three follow-up visits (weeks four, eight, and 12).8 Participants in the alternative titration arm experienced a significantly greater reduction in LDL-C levels compared to those in the standard arm. At week four, a higher proportion of patients on rosuvastatin 15mg achieved target lipid levels compared to those on 10mg (81% vs 67%). The safety and tolerance of both doses were comparable. 8

The authors concluded that rosuvastatin 15mg was a more effective initial dose compared to 10mg, with significantly more patients reaching target LDL-C levels and fewer dose adjustments needed. 8

Conclusion

The introduction of new 15mg and 30mg rosuvastatin dosages marks a significant advancement in the treatment of dyslipidaemia, particularly for patients at varying CV risk levels. These intermediate dosages offer a personalised approach to therapy, enhancing the likelihood of achieving target LDL-C levels. Studies have shown that these new dosages improve lipid profile outcomes and reduce the need for frequent dose adjustments, providing an effective and safe option for initial treatment.

References are available on request. SF

STELLAR PERFORMER

OF ROSUVASTATIN

in 30’s

CARDIOLOGY | Arrythmias

This article was independently sourced by Specialist Forum.

Heart Trouble? Flecainide’s got the rhythm

Cardiovascular diseases

(CVDs) are the leading cause of death in sub-Saharan Africa, accounting for ~37% of deaths in the region. An estimated 32 million people in the region are living with diagnosed CVDs, with many more likely undiagnosed. Each year, ~3.6 million new cases are reported.1

According to Yuyun et al (2020), all major structural CVDs are linked to cardiac arrhythmias and as CVDs increase in subSaharan Africa, it is likely that the burden of arrhythmias is also rising. Furthermore, state the authors, arrhythmias are ‘probably underdiagnosed’ in sub-Saharan Africa.1

Some of the reasons for this include the fact that the region faces significant challenges in managing CVDs due to insufficient health infrastructure, including limited arrhythmia services.1

The region lacks specialist cardiac services, with many countries having fewer than five physicians per 10 000 people and 18% lacking a registered cardiologist.1

High costs and limited health insurance systems further exacerbate the issue, making arrhythmia management unaffordable for most. Additionally, there is a severe shortage of epidemiological data on arrhythmias, hindering effective public health planning and resource allocation, they conclude.1

A national registry study assessed treatment modalities for atrial fibrillation (AFib) in South Africa. Results showed that hypertension was the most common clinical characteristic (65.9%). Rhythm control, using class IC and III anti-arrhythmic drugs (AADs), was pursued in 36.1% of patients, while rate control, mainly with betablockers, was used for the rest. 2

Warfarin was used by 75.2% for stroke prevention. AFib-related complications included heart failure (HF, 32.5%), stroke (8.3%), and transient ischaemic attack (5.3%).2

Therapeutic success was achieved in 86.8% of patients based on clinical judgment but only 70.2% met the electrocardiogram heart rate criterion of ≤80 bpm. The study highlighted a lack of strict rate control application, with results comparable to international data. 2

What are the most common arrythmias seen in clinical practice?

Arrhythmias are broadly categorised into bradyarrhythmias and tachyarrhythmias based on heart rate. They can also be classified according to their origin, transmission pathways, and associated syndromes. 3

The clinical presentation of arrhythmias varies widely, ranging from asymptomatic cases to sudden cardiac arrest. Due to their paroxysmal nature, arrhythmias can be intermittent, making it difficult to accurately determine their prevalence. 3

Tachyarrhythmia, defined by a ventricular heart rate of ≥100 beats per minute, is further classified by its origin into supraventricular tachycardia (SVT), and ventricular tachycardia (VT). 3

SVT originates above the atrioventricular (AV) node and includes conditions such as AFib, atrial flutter, atrial tachycardia

(AT), atrial premature complex, AV nodal re-entrant tachycardia, AV reentrant tachycardia (AVRT), and AV junctional extrasystoles. 3

VT, originating below the AV node, includes ventricular fibrillation (VFib), premature ventricular contractions (PVCs), and both sustained and non-sustained VT. 3 AFib is the most common type of cardiac arrhythmia and is the leading cardiac cause of stroke. Risk factors for AFib include advanced age, high blood pressure, underlying heart and lung disease, congenital heart disease, and increased alcohol consumption. 4

AADs still the mainstay of arrhythmia treatment

According to Kowey and Naccarelli (2024), ‘misguided advice’ about the role of AADs has led to a decline in the use of these agents in the treatment of arrhythmias. The authors stress that AADs have been, and will remain, the mainstay of chronic therapy of patients living with cardiac arrhythmias. 5 In sub-Saharan Africa, AADs are available in most countries. Digoxin and amiodarone were available in all surveyed countries, followed by flecainide (80%), sotalol (75%), propafenone (22%), quinidine (17%), and mexiletine (4%).1

Targeted ablative procedures for arrhythmias are a safe and effective option for patients with AFib unresponsive

Recommended as a treatment option for restoring and maintaining Sinus Rhythm (SR) in patients with Paroxysmal Atrial Fibrillation (PAF) and minimal or no

(ESC) Guidelines 2020

Tambocor is indicated for Symptomatic treatment in patients with Idiopathic PVC’s and no structural heart disease2,3

to medication and have seen rapid technological growth and increasing clinical interest in recent years. Reports highlight their effectiveness, quick procedural times, low risks, and fast recovery. 6

Older drugs coming to the fore

Flecainide is a class IC AAD that was first synthesised in 1972. It was approved by the American Food and Drug Administration in 1984 for the suppression of sustained VT. Approval was based on the results of the Suppression of ventricular ectopic depolarisations by flecainide acetate, a new antiarrhythmic agent study, which showed significant suppression after one and two weeks of treatment (94.4% and 93.3%, respectively without significant adverse events (AEs).7,8

In South Africa, flecainide is indicated for the treatment of sustained ventricular arrythmias (VAs), AVNRT, Wolff-ParkinsonWhite Syndrome, and similar conditions involving accessory pathways with anterograde or retrograde conduction.9

It is also indicated for paroxysmal AFib in patients experiencing disabling symptoms, with a higher likelihood of success in arrythmias of recent onset. Furthermore, flecainide is indicated for treating PVCs and non-sustained VT when these conditions cause disabling symptoms. Flecainide can also be used to maintain normal rhythm after cardioversion using other methods.9

Mechanism of action of flecainide

By slowing conduction, flecainide reduces the atrial wavelength, thereby impeding the maintenance of AFib. This effect is linked to its ability to decrease intracellular calcium accumulation by blocking sodium channels, which mitigates oxidative stress and atrial remodeling. 4

Maintaining sinus rhythm

A Randomized Comparison of Amiodarone and Class IC Antiarrhythmic Drugs to Treat Atrial Fibrillation in Patients Paced for Sinus Node Disease: The Prevention Investigation and Treatment: A Group for Observation And Research On Atrial Arrhythmias (PITAGORA) Trial as well as the FLEC-SL trials underscore its effectiveness in maintaining sinus rhythm, with flecainide proving non-inferior to amiodarone in some cases.10,11,12

The PITAGORA study assessed whether class IC AADs like flecainide and propafenone were noninferior to amiodarone in patients with sinus node disease. Patients were randomised in a 1:1 ratio to receive either amiodarone or class IC AADs.10

Over an average follow-up of 20-months, the primary endpoint (mortality, permanent AT, CV hospitalisation, atrial cardioversion, or AAD change) occurred in 30.7% of patients on class IC AADs and 40% of those on amiodarone.11

One-year freedom from AT episodes lasting >10 minutes, one day, and seven days was 40%, 73%, and 91% for amiodarone and 28%, 78%, and 86% for class IC AADs.11

More recently, Rillig et al (2024) evaluated the safety and efficacy of rhythm control therapy with flecainide and propafenone in patients with early recurrence of AFib as part of the The Early Treatment of Atrial Fibrillation for Stroke Prevention Trial 12

The study included 1395 participants and focused on two primary outcomes: Safety, defined as death, stroke, or serious AEs, and efficacy, defined as CV death, stroke, and hospitalisation for worsening heart failure or acute coronary syndrome.12

The analysis revealed that the primary efficacy outcome occurred less frequently in patients treated with flecainide or propafenone (3/100 patient-years) compared to those who did not receive flecainide or propafenone (4.9/100 patient-years).12

Additionally, the primary safety outcomes were lower in the flecainide and propafenone group (2.9/100 patient-years) compared to the non-AAD group (4.2/100 patient-years). The rate of maintaining sinus rhythm at two years was comparable between the AAD group (88%) and the non-AAD group (82%).12

Ventricular tachycardia

In terms of VT, flecainide’s role is complex. The Cardiac Arrhythmia Suppression Trial (CAST) revealed that flecainide, when used for asymptomatic VAs post-myocardial infarction, increased the risk of arrhythmia-related and all-cause mortality, leading to its premature discontinuation in some patients. However, Kowey and Naccarelli point out that in the post-CAST era, data suggest that flecainide may be used in patients with minimal coronary artery disease.5,10

Acute setting

In acute settings, flecainide’s efficacy has also been shown. Both oral and intravenous (IV) forms of the flecainide have proven effective in converting recent-onset AFib to sinus rhythm. Notably, oral flecainide administered as a single loading dose (so-called ‘pill-in-the-pocket’) has been shown to be more effective than IV amiodarone within eight hours.7

Conclusion

CVDs are a leading cause of death in sub-Saharan Africa, with a rising prevalence of cardiac arrhythmias linked to the increasing CVD burden. AADs, particularly flecainide, are essential for treating these conditions. In arrhythmia patients with minimal or no structural heart disease, studies demonstrate flecainide’s efficacy and safety. Addressing healthcare gaps and improving access to AADs could significantly enhance arrhythmia management in sub-Saharan Africa. References are available on request. SF

Obesity a ‘huge’ obstacle

An estimated one billion people worldwide are obese –>650 million adults, >340 million adolescents and >39 million children. Around 50% of South African adults are either overweight (23%) or obese (27%). By 2025, >167 million people will be directly affected by overweight or obesity, which increases the risk of cardiovascular disease (CVD) and places a strain on healthcare resources.

Overweight is defined as a body mass index (BMI) of ≥25kg/m2, while obesity is defined as a BMI ≥30 kg/m2 . Obesity is associated with the development of heart failure (HF), coronary heart disease, sudden cardiac death, and atrial fibrillation (AFib). 2,3,4

How does obesity affect the CV system?

Obesity accelerates the onset of CVD, leading to a shorter lifespan and increased lifetime CVD burden compared to individuals with normal weight. It harms the CV system both directly and indirectly, influencing risk factors and sleep disorders linked to obesity.4,5

The impact of obesity on the CV system is multifaceted. Excessive adipose tissue functions as an endocrine organ, releasing adipokines like leptin and interleukin 6, which regulate energy balance and insulin sensitivity. However, overproduction of adipokines in obesity creates an imbalance, fostering insulin resistance, metabolic syndrome, and inflammation, evidenced by high C-reactive protein levels. 4

This inflammation contributes to endothelial damage, vascular hypertrophy, and increased CVD risk. Additionally, obesity leads to left ventricular hypertrophy (LVH) due to increased plasma renin, aldosterone activity, and insulin levels. The resulting left ventricular dilation and eccentric LVH increase the risk of HF, AFib, and ventricular arrhythmias.4

To reduce the impact of obesity-associated CVD risk, international obesity management guidelines universally recommend multicomponent lifestyle interventions, including diet, physical activity, and behaviour change support for six to 12 months.6

While lifestyle modifications remain the primary treatment for obesity, anti-obesity medications (AOMs) offer supplemental options. Pharmacotherapy is recommended for individuals with a BMI of ≥30 kg/m² or ≥27 kg/m² with at least one weight-related comorbidity, such as CVD, type 2 diabetes (T2DM), hypertension, or dyslipidaemia. It is also suitable for those who cannot achieve significant weight loss through lifestyle changes alone.7

Do AOMs increase the risk of CVD?

Over the past 20 years, numerous anti-obesity medications (AOMs) have been withdrawn due to CV safety concerns. Phentermine, approved in 1959, however has been associated with a reduction in low-density lipoprotein (LDL) cholesterol and an increase in high-density lipoprotein (HDL) cholesterol and remains widely used worldwide.8

In South Africa, a 2016 study revealed that phentermine was the most prescribed AOM, accounting for 92.44% of prescriptions,

followed by orlistat, phendimetrazine, D-norpseudoephedrine, and diethylpropion.9

In South Africa, phentermine is approved as a short-term adjunct to a comprehensive weight reduction programme that includes exercise, dietary changes, and behaviour modification for obese patients with a BMI of ≥30kg/m² who have not achieved satisfactory results with lifestyle changes alone. It may also be prescribed to those with a lower BMI if other risk factors are present.10

For adults with a BMI ≥35 kg/m² who have failed non-surgical methods, bariatric surgery may be an option. Guidelines also advocate for managing obesity as a chronic disease with multidisciplinary teams. 6

To reduce the impact of obesityassociated CVD risk, international obesity management guidelines universally recommend multicomponent lifestyle interventions

Phentermine is contraindicated in patients with pulmonary artery hypertension, arterial hypertension, cerebrovascular disease, cardiac disease including arrhythmias, and advanced arteriosclerosis. It is also contraindicated in individuals with known hypersensitivity to phentermine or sympathomimetic drugs, hyperthyroidism, agitated states, or a history of psychiatric disorders, including anorexia nervosa and depression.10

Additionally, it should not be used by those with glaucoma, a history of drug or alcohol abuse or dependence, obstructive uropathy, poorly controlled epilepsy, or those undergoing concomitant treatment with monoamine oxidase inhibitors or within 14 days following their administration.10

How does weight-loss benefit CV health?

Weight loss offers significant benefits across various health parameters, particularly in managing CVD, T2DM, hypertension, cholesterol levels, glycaemic control, and insulin resistance.11

Weight loss interventions have shown a promising impact on reducing the incidence of CVD. Studies indicate a mean weight reduction of about 2.2kg, with evidence suggesting that

weight loss can lead to a lower incidence of CVD over time.11 At one year, the predicted reduction in CVD incidence is ~20.2 per 1000 person-months, increasing to 39.3 per 1000 person-months at five years. This benefit is sustained despite some weight regain.11

Weight loss interventions are associated with lower incidence rates of T2DM. The mean weight difference of 4.1kg between intervention and control groups leads to a reduction in diabetes incidence. Over time, this advantage persists, with a predicted lower incidence of ~62 per 1000 person-months one year after weight loss, maintaining a similar reduction at five years.11

While data on hypertension incidence is limited, evidence suggests that weight loss can reduce hypertension rates. The reduction in hypertension incidence is about 67 per 1000 person-months, and although data on long-term remission is sparse, weight loss is beneficial.11

Weight loss results in improvements in cholesterol levels11p6 . The average reduction in total cholesterol/HDL ratio is about 1.2. The benefit is sustained over five years, with weight regain impacting this advantage minimally.11

Weight loss improves glycaemic control, with reductions in HbA1c levels. The modeled estimate suggests a decrease in glycemic control by ~0.26 units at one- and five-years post weight-loss. Weight-loss also decreases insulin resistance. The reduction in insulin resistance is notable, with a sustained benefit over three years.11

Cardiology is entering a new era in the fight against obesity

According to Sattar et al, cardiology is entering a new era in the fight against obesity. With many patients at risk of or living with CVD also struggling with overweight and obesity, and often facing multiple weightrelated comorbidities, evidence-based weight loss treatments that address major adverse CV events and other weight-related outcomes hold transformative potential.12

This should encourage cardiologists to integrate weight-related interventions earlier in the disease course, aiming to prevent or delay the onset of adverse CVD and enhance patients’ quality of life.12

If obesity is not managed effectively, rates of multimorbidity, stroke, and HF could rise, potentially undoing the progress made over the past few decades. It is imperative for the cardiology community to collaborate with other medical fields to address the public health challenge of obesity and reduce both CV and non-CV complications associated with excess adiposity in this new era.12

References are available on request. SF

This article was independently sourced by Specialist Forum.

From earaches to sneezes: Common ENT complaints in primary care

Ear, nose, and throat (ENT) diseases are common in primary care settings, affecting individuals across all age groups. These conditions can range from mild infections to more severe chronic diseases. The most prevalent ENT diseases managed in primary care include otitis media (OM), sinusitis, allergic rhinitis (AR), and pharyngitis.

Otitis media

OM, an infection or inflammation of the middle ear, is particularly common in children. It is often caused by bacterial or viral infections and can result in ear pain, fever, and hearing loss. Acute OM is characterised by the rapid onset of symptoms, while otitis media with effusion involves fluid accumulation without signs of acute infection. Management typically includes pain relief,

observation, and in some cases, antibiotics. Chronic cases may require referral to a specialist for further evaluation and treatment.

Sinusitis

Sinusitis, or rhinosinusitis, is the inflammation of the sinus cavities, often due to infection, allergies, or other factors. Acute sinusitis presents with symptoms such as nasal congestion, facial pain, and purulent nasal discharge lasting less than four weeks. Chronic sinusitis persists for more than 12-weeks and may involve nasal polyps. Treatment includes nasal decongestants, saline irrigation, and antibiotics for bacterial infections. Chronic cases may benefit from corticosteroids or surgical intervention.

Allergic rhinitis

AR is an inflammatory condition of the nasal mucosa triggered by allergens such as pollen, dust mites, or pet dander. Symptoms include sneezing, nasal congestion, runny nose, and itchy eyes. Management involves avoiding known allergens, using antihistamines, nasal corticosteroids, and immunotherapy in severe cases. Education on environmental control measures is also crucial for effective management.

Pharyngitis

Pharyngitis, or sore throat, is inflammation of the pharynx, often caused by viral or bacterial infections. Viral pharyngitis is more common and usually self-limiting, while bacterial pharyngitis, such as streptococcal pharyngitis, requires antibiotic treatment. Symptoms include throat pain, fever, and swollen lymph nodes. Management focuses on symptomatic relief with analgesics, throat lozenges, and adequate hydration. Rapid antigen detection tests and throat cultures help in diagnosing streptococcal infections.

Conclusion

ENT diseases are frequently encountered in primary care and can significantly impact patients’ quality of life. Effective management involves accurate diagnosis, appropriate treatment, and patient education. Primary care providers play a crucial role in the early detection and management of these conditions, ensuring timely referral to specialists when necessary. References are available on request. SF

OPHTHALMOLOGY | Dry eye disease

This article was independently sourced by Specialist Forum.

Eyeing better health in diabetes:

How PG-HPG nanoemulsion artificial tears tackle dry eye

By 2030, the global prevalence of diabetes is projected to reach 643 million cases, with Africa seeing the most significant increase (a 129% rise), leading to ~55 million cases by 2045. Africa also currently has the highest number of undiagnosed diabetes cases (53.6%). Diabetes is associated with a high risk for various comorbidities, including cardiovascular, kidney, and ocular diseases, such as dry eye disease (DED).1,2,3

Dry eye disease overview

DED is the most common disorder impacting tear production and the ocular surface. It is characterised by a loss of tear film homeostasis and related ocular symptoms. The onset of DED is influenced by tear film instability, hyperosmolarity, ocular surface inflammation, damage, and neurosensory abnormalities. 2,4

Prevalence of DED in individuals living with diabetes

Among individuals living with diabetes, the prevalence of DED is estimated to range between 30% and 38.3%. In these individuals, DED is often caused by peripheral neuropathy, lacrimal gland dysfunction, inflammatory changes, and systemic hyperosmotic disturbances due to hyperglycaemia.2,3,5

The incidence of DED is particularly high - reaching 67% - among those with type 2 diabetes (T2DM), which constitutes >90% of diabetes cases, especially in those with uncontrolled diabetes (HbA1c >8%) and long-standing diabetes (over 10 years, 68%). Long-standing diabetes can damage the microvasculature of the lacrimal gland, affecting tear production.1,6,7

A study by Naik et al found that in most diabetic individuals, DED was primarily caused by meibomian gland dysfunction (MGD, 44%) followed by blepharitis (23.7%).7

MGD results from the malfunction of the meibomian glands, which secrete oils that prevent tear film evaporation. When these glands are blocked or dysfunctional, the lipid layer of the tear film becomes deficient, leading to increased tear evaporation and dry eye symptoms.9

Blepharitis, characterised by inflammation of the eyelid margins, can present as either anterior or posterior inflammation and typically affects both eyes, leading to irritation at the lid margins, flaking, and crusting of the lashes.10

Impact of DED on quality of life

DED significantly impacts individuals’ quality of life (QoL), manifesting in symptoms such as stinging, watering, redness, and irritation of the ocular surface, particularly the cornea. Individuals living with diabetes and DED often experience additional symptoms like itching and burning. These symptoms severely affect QoL, comparable to conditions like angina, hip fractures, or dialysis.6,8

DED not only impacts the physical wellbeing of individuals but also their social and psychological functioning. The most significant costs associated with DED are indirect, primarily due to reduced work productivity.11

Psychologically, individuals with DED and diabetes have higher rates of depression and anxiety compared to the general population. In a study assessing the relationship between depression and major ocular diseases, Jonas et al found that DED was the only ocular disorder associated with an increased rate of depression.12

Management challenges

Managing DED is complex due to its multifactorial nature, as noted by the Tear Film and Ocular Surface Society. The primary goal of treatment is to restore tear film and ocular surface homeostasis. Treatment often involves multiple therapies targeting different aspects of the condition. Furthermore, the treatment of DED typically requires ongoing management rather than short-term solutions.11

The 2024 American Academy of Ophthalmology (AAO) recommends

that individuals with mild DED symptoms undergo a trial of artificial tears once other potential causes of ocular irritation have been ruled out. For mild cases, artificial tears with preservatives may suffice, but for those using them frequently (more than four times a day), preservative-free options are recommended.12

For moderate DED, the AAO suggests additional treatments, including topical anti-inflammatories, surgical procedures, other ophthalmic solutions, corticosteroids, oral fatty acid supplements, aqueous nasal spray, or punctal occlusion. Non-invasive options such as eyeglass side shields and moisture chambers can also be beneficial.12

For severe DED, the addition of permanent punctal occlusion may be considered. Thermal cautery is generally more effective and costefficient than laser cautery for achieving permanent occlusion.12

Efficacy of artificial tears

There is strong evidence that artificial tears can relieve dry eye symptoms within a month of regular use, typically applied about four times a day. However, significant improvements in signs of the condition generally take several months.13

According to Silverstein et al, most artificial tears target either the lipid or aqueous layer of the tear film. However, a lubricant addressing all layers is needed to effectively manage DED symptoms.14

Propylene Glycol-HydroxyPropyl Guar (PG-HPG) nanoemulsion lubricant eye drops are designed to address all layers of the tear film, utilising propylene glycol as the main demulcent and featuring a higher concentration of HPG gelling technology compared to previous formulations.14

These drops also contain a lipid excipient in smaller nano-sized droplets, improving lipid surface coverage and offering a more translucent appearance. They are intended for individuals with dry eye resulting from either lipid or aqueous deficiency and are suitable for individuals with mixed DED.14

After application, PG-HPG nanoemulsion forms a protective viscoelastic barrier on the eye’s surface. As the pH normalises and sorbitol dilutes, this barrier strengthens, gradually releasing lipids into the tear film.14

Dimyristoyl phosphatidylglycerol, an anionic phospholipid in PG-HPG nanoemulsion, migrates to the surface of the tear film, merging with existing lipids to fill gaps caused by MGD and lipid insufficiency. This formulation helps restore the complete tear structure, alleviating symptoms and maintaining a healthier ocular surface.14

How safe and effective are PG-HPG nano-emulsion artificial tears?

Silverstein et al assessed how rapidly a single drop of PG-HPG nano-emulsion can relief symptoms. On Day 1, the median reduction in symptom scores was greater than one point across all post-dose time points. Among individuals with a baseline symptom score of six to 10, 67.2% to 77.0% reported a reduction to zero to five within eight hours.14

The median symptom score for aqueousdeficient dry eye individuals improved from −1 at zero hours to −2.5 at four hours, while evaporative and mixed subtypes showed similar improvements.14

Artificial tears can relieve dry eye symptoms within a month of regular use, typically applied about four times a day

In Part 1, a significant increase in average LLT was observed 15 minutes after the instillation of the nanoemulsion drop, particularly in the overall and inferior third of the tear film for subjects with baseline LLT values <50nm. No increase in LLT was found after using the non-emollient drop. Symptoms of dry eye improved for up to six hours following the instillation of both drops.15 In Part 2, after one month of using the nanoemulsion drop four times daily, individuals reported a statistically and clinically significant improvement in dry eye symptoms.15

Weisenberger et al concluded that the nanoemulsion eye drop can effectively increase LLT and alleviate dry eye symptoms in individuals with low baseline LLT levels.15

Managing DED in individuals living with diabetes

Furthermore, >80% of individuals reported a soothing sensation lasting throughout the eight-hour evaluation, with median soothing scores consistently around three.14

Tolerability was high, with >92% of individuals reporting minimal discomfort. Subgroup analyses confirmed these findings across different dry eye subtypes, demonstrating the eye drops’ effectiveness and tolerability.14

Silverstein et al concluded that PGHPG nanoemulsion consistently reduced the symptoms associated with DED in all individuals, regardless of the disease subtype, thereby providing instant, immediate, and all-day symptom relief.14

Weisenberger et al evaluated the effects of a single drop of two ocular lubricants - a nanoemulsion and a non-emollient - on tear film lipid layer thickness (LLT) and symptoms of dry eye.15

The study consisted of two parts: a cross-over comparison measuring LLT and dry eye symptoms at baseline and at intervals up to six hours after instillation, and a one-month observational study assessing LLT and symptoms after daily use of the nanoemulsion drop.15

The American Diabetes Association (ADA) advises that individuals undergo a dilated eye examination soon after receiving a diabetes diagnosis. Many individuals living with T2DM diabetes may have been living with the condition for years prior to diagnosis, which could result in unnoticed ocular damage. The initial examination should be comprehensive and include pupil dilation. Based on the findings, the physician may recommend follow-up exams every one to two years. If diabetic eye disease is detected, more frequent monitoring may be necessary. The ADA recommends using artificial tears regularly to maintain adequate ocular moisture.16,17

Conclusion

The efficacy of PG-HPG nanoemulsion artificial tears has been demonstrated across all subtypes of DED. The ADA recommends artificial tears for individuals living with diabetes and DED. As the prevalence of diabetes continues to rise globally, especially in Africa, the need for effective management of associated comorbidities, such as DED, becomes increasingly critical. PG-HPG nanoemulsion offers a comprehensive solution by addressing both lipid and aqueous deficiencies in the tear film, resulting in rapid symptom relief and sustained ocular surface protection. The consistent improvement in tear film lipid layer thickness and significant reduction in dry eye symptoms highlight the potential of PG-HPG nanoemulsion as a valuable therapeutic option for managing DED in individuals living with diabetes, thereby enhancing their QoL and mitigating the ocular complications of diabetes. References are available on request. SF

ONLINE CPD: UROLOGY | LUTS

Exploring BPH treatments: Mono- vs combo therapy

Benign prostatic hyperplasia (BPH) is a common condition in older men, characterised by the non-cancerous enlargement of the prostate, leading to bladder outflow obstruction and lower urinary tract symptoms (LUTS).

BPH’s prevalence increases with age, affecting 50%-60% of men in their 60s and up to 90% of men >70-years. Symptoms of BPH, resulting from both static (prostate tissue compression) and dynamic (increased smooth muscle tone) mechanisms, can significantly impact quality of life (QoL), affecting selfesteem, sexuality, and daily activities.

The decision to treat BPH depends on symptom severity, impact on daily life, and the potential for complications like acute urinary retention. Management options include watchful waiting, pharmacotherapy,

and surgery. Pharmacotherapy, particularly with α1-blockers like tamsulosin and 5-alpha reductase inhibitors (5-ARIs) like dutasteride, is recommended for patients with bothersome symptoms. Combination therapy, using both α1-blockers and 5-ARIs, has been shown to be more effective than monotherapy in reducing symptom progression and improving QoL.

The four-year CombAT study demonstrated that combination therapy significantly reduces the risk of AUR, BPHrelated surgery, and clinical progression compared to monotherapy. Patients on

combination therapy also reported higher satisfaction and better outcomes in both voiding and storage symptoms.

Surgical options remain the gold standard for severe cases or when pharmacotherapy is insufficient. However, surgery carries risks, including bleeding and retrograde ejaculation, which should be discussed with patients. Overall, combination therapy offers superior symptom relief and long-term control for BPH, improving patient outcomes and QoL.

To access the article and quiz, go to https:// www.medicalacademic.co.za/courses/ SF

BPH: Benign Prostatic Hyperplasia. #calculated on originator

%.

0,5 mg/0,4 mg hard gelatine capsules. Each hard gelatine capsule contains 0,5 mg dutasteride and 0,4 mg tamsulosin hydrochloride (equivalent to

INFECTIOUS DISEASES | Hepatitis

This article was independently sourced by Specialist Forum.

Early detection saves lives: The critical role of screening and testing for hepatitis C

The World Health Organization (WHO) warns that mortality from viral hepatitis is on the rise. In 2022, 1.3 million people died due to viral hepatitis, with an estimated 240 000 deaths attributed to hepatitis C (hep C) infection and associated complications, such as cirrhosis and liver cancer.1,2

According to the South African National Department of Health (NDoH), liver disease caused by chronic viral hepatitis infection is a silent and neglected contributor to morbidity and mortality in the country. This burden is exacerbated by insufficient screening, limited access to

care and treatment, inadequate disease surveillance, and a lack of human and financial resources. 3

Who should be screened and tested for hep C?

To eliminate hep C infection in South Africa, which is transmitted via parenteral and

non-parenteral routes, it is essential to enhance seroprevalence surveillance and increase screening among high-risk groups, state the NDoH. 3

The purpose of screening is to detect hep C viraemia. Key populations that should be screened include people who inject drugs (PWID), people in prisons, and men

INFECTIOUS DISEASES | Hepatitis C

who have sex with men, particularly those living with HIV. 2,4

According to the NDoH, at risk groups also include:3

_ Recipients of blood, blood products, and solid organ transplants in the country before 1992

_ Individuals exposed to unsafe medical injection practices

_ Healthcare workers with occupational exposure (eg needle stick injuries), Individuals undergoing chronic haemodialysis (up to 10% risk) Those involved in high-risk or traumatic sexual practices

_ Users of intranasal cocaine

_ Those undergoing tattooing, body piercing, acupuncture, or surgical procedures (including dental and orthodontic procedures without proper sterilisation)

_ Individuals participating in traditional or cultural practices (eg circumcision, scarification rituals).

According to Sonderup et al, hep C screening should also form part of antenatal care, particularly for HIV-positive women, as well as for children born to hep C-positive mothers. Screening for the general population should leverage existing community-based or facility-based testing opportunities, such as those provided at antenatal clinics, HIV or tuberculosis clinics, and drug-treatment services. 4

What are some of the signs and symptoms that should raise suspicion of possible hep C infection?

Recently acquired hep C infections are usually asymptomatic and rarely lead to symptomatic acute infection. Following infection, ~30% of infected individuals spontaneously clear the virus within six months without treatment, with a median time to clearance of 16.5 weeks. 2

The remaining 70% of affected individuals will develop chronic hep C infection. Importantly, individuals who have cleared their infection, either spontaneously or through treatment, are not immune to the virus and can be reinfected if they have ongoing risk and exposure. 2

Acute hep C infection may initially present with symptoms such as malaise, nausea, and right upper quadrant pain, followed by dark urine and jaundice, which clinically resemble other acute viral hepatitis cases. 5 Chronically infected individuals often remain asymptomatic or may experience non-specific symptoms such as fatigue, intermittent right upper quadrant pain, joint pain, and a general feeling of unwellness that impacts their quality of life. 5

In individuals with cirrhosis due to hep C infection, 10% to 20% may clinically decompensate within five years. This is characterised by the development of complications such as portal hypertension, oesophageal varices, ascites, coagulopathy, encephalopathy, or hepatocellular carcinoma. 5

Physical examination at this stage may reveal signs typical of chronic liver disease, including caput medusae, spider angiomas, palmar erythema, asterixis, anasarca, and a fluid thrill. Additionally, patients may manifest signs of various extrahepatic manifestations such as mixed cryoglobulinemia, membranoproliferative glomerulonephritis, porphyria cutanea tarda, lichen planus, neurocognitive changes, insulin resistance, and B cell lymphoproliferative disorders. 5

C testing and treatment follows a stepwise process:2

Step 1

The purpose of screening is to detect hep C viraemia

Who should be tested?

The WHO recommends offering hep C testing to all adults in settings where the prevalence of hep C viral antibodies in the general population >2%, and focused testing in all settings for the most affected populations. A 2015 meta-analysis suggests an overall hep C viral prevalence of 2.98% in sub-Saharan Africa. 2,6 Some countries also include other populations in their focused testing approach, such as migrants, homeless people and the children of parents with hep C.1

The WHO emphasises that testing should be voluntary and should not contribute to further stigmatisation of populations at ongoing risk. Testing should be integrated with evidence-based primary prevention services that reduce transmission risks, and it should facilitate access to appropriate treatment and linkage to care. 2

How to test and treat

The WHO summary algorithm for hep

Conduct anti-hep C antibody testing

_ Use a rapid diagnostic test or laboratory-based immunoassay.

Step 2 If anti-hep C+ proceed to viral load testing

_ Use lab-based hep C RNA (qualitative or quantitative) or hep C core antigen (cAg) assays, or point-of-care hep C RNA assays.

Step 3 Interpret fesults

_ If RNA test or cAg is negative: No infection.

_ If RNA test or cAg is positive: Hep c viraemic infection.

Step 4 Offer and start treatment

_ Eligible Patients: Adults (≥18 years) and adolescents (12- to 17-years).

_ Assessment prior to treatment initiation

• Liver fibrosis: Assess using noninvasive tests (eg aspartate aminotransferase to platelet ratio index, Fibrosis-4) to determine if there is cirrhosis.

• Other considerations: Evaluate comorbidities, pregnancy status, and potential drug-drug interactions.

_ Treatment regimens

• In South Africa, sofosbuvir/velpatasvir is indicated for the treatment of chronic hep C infection irrespective of genotype in treatment naïve or treatment experienced patients aged ≥12-years and weighing at least 30 kg:7

• Without cirrhosis or with compensated cirrhosis

• With decompensated cirrhosis in combination with ribavirin.

Step

5 Assess cure

_ Sustained virological response (SVR): Evaluate at 12 weeks post-treatment using hep C RNA SVR, qualitative or quantitative nucleic acid test.

_ Monitoring: For individuals with cirrhosis, detect hepatocellular carcinoma every six months using ultrasound or alfafetoprotein liver function test.

Conclusion

Early detection and treatment can greatly reduce hep C transmission and prevent complications like cirrhosis and liver cancer. Integrating hep C screening and testing into existing health services and ensuring voluntary, non-stigmatising practices will be vital steps toward achieving hep C elimination. References are available on request. SF

EPCLUSA® is indicated for the treatment of chronic hepatitis C infection irrespective of genotype in treatment naïve or treatment experienced patients aged 12 years and older and weighing at least 30 kg:

- without cirrhosis or with compensated cirrhosis

- with decompensated cirrhosis in combination with ribavirin 1

PRESCRIBING WITH CONFIDENCE

a,b,c 1,2,3

Proven cure ratec: 98,9 % in real-world analysis2,3

Suitable for patients with various levels of liver disease severityb,d 2,3

Pan-genotypic and pan-fibroticb,d 3

1 tablet once daily, with or without food, for 12 weeks1

HAVE CONFIDENCE IN CUREb WITH EPCLUSA®

1,2,3

Footnotes: aDespite unknowns in baseline characteristics of some patients, such as: HCV genotype, fibrosis stage, former/current IV drug use, PPI use at baseline and treatment history.3 bA large-cohort international real-world study showed that patients with unknown genotype (n = 42), unknown fibrosis score (n = 82) and unknown treatment history (n = 33) were cured with EPCLUSA® for 12 weeks. Cure is defined as SVR i.e., undetectable HCV RNA after treatment completion.3,4 cCases of HBV reactivation, some of them fatal, have been reported during or after treatment with direct acting antiviral agents including EPCLUSA®. HBV screening should be performed in all patients before initiation of treatment. Treatment with EPCLUSA® should not be initiated in patients who screened positive for hepatitis B virus infection. HBV/HCV coinfected patients are at risk of HBV reactivation, and should therefore be monitored and managed according to current clinical guidelines.1 dPatients with decompensated cirrhosis use EPCLUSA® + ribavirin for 12 weeks.1

Abbreviations: HCV = Hepatitis C Virus; RNA = Ribonucleic acid; IV = Intravenous; PPI = Proton pump inhibitor; SVR = Sustained virological response; HBV = Hepatitis B virus.

References: 1. Epclusa Professional Information approved by the medicine’s regulatory authority. 10 March 2022. 2. Lawitz E, Bourliere M, Han L, McNally J, Stamm LM, Brainard DM, et al. Treatment with SOF/VEL or SOF/VEL/VOX is well tolerated and results in high SVR12 in genotype 1-6 HCV-infected patients with minimal fibrosis: a retrospective analysis of the ASTRAL and POLARIS clinical studies. Poster THU-273 presented at the International Liver Congress 2017, April 19–21, Amsterdam, The Netherlands. Available at: https://www.natap.org/2017/EASL/EASL_07.htm [Accessed 24 March 2022]. 3. Mangia A, Milligan S, Khalili M, Fagiuoli S, Shafran SD, Carrat F, et al. Global real-world evidence of sofosbuvir/ velpatasvir as simple, effective HCV treatment: Analysis of 5552 patients from 12 cohorts. Liver Int 2020;40:1841–1852. 4. National Guidelines for the Management of Viral Hepatitis. Department of Health Republic of South Africa Available at: https://sahivsoc.org/Files/SA%20NDOH_Viral%20Hepatitis%20guideilnes%20final_.pdf [Accessed 10 March 2022]. For full prescribing information refer to the professional information approved by the Medicines Regulatory Authority. S4 EPCLUSA® 400 mg/100 mg film-coated tablets. Reg. No.: 51/20.2.8/0872. Each film-coated tablet contains 400 mg sofosbuvir and 100 mg velpatasvir. Gilead Sciences South Africa (Pty) Ltd., Reg No.: 2014/063761/07, Ground Floor Mac Mac Building, Maxwell Office Park, Magwa Crescent, Waterfall. (Tel: +27 10 346 1920). For any adverse events, please contact: Safety_FC@gilead.com or drugsafetysouthafrica@gilead.com | EPCLUSA®, the EPCLUSA® Logo, GILEAD and the GILEAD Logo are trademarks of Gilead Sciences, Inc. or its related companies. All other trademarks referenced herein are the property of their respective owners. ©2023 Gilead Sciences, Inc. All rights reserved. Date of preparation: 02/2023 | Job code: ZA-EPC-0022

This article was independently sourced by

Causes, mechanisms, and progression Understanding HCC:

October is Liver Cancer Awareness Month. In 2020, liver cancer ranked as the sixth most prevalent malignant tumour and the third cause of cancer-related morbidity.

Hepatocellular carcinoma (HCC) comprises ~90% of primary malignant liver tumours.

Between 70% and 90% of patients living with HCC have an established history of chronic liver disease or liver cirrhosis.1,2

The prognosis of HCC patients is relatively poor compared with other gastrointestinal (GI) tract tumours, with an estimated fiveyear survival rate of <20%. In patients who are not transplant candidates, HCC is even more lethal, with a five-year survival of <5%.1,3

The main drivers of chronic liver diseases and cirrhosis include viral hepatitis (predominantly hepatitis B [HBV] and C [HCV] subtypes), while the leading non-viral causes include non-alcoholic liver disease (NAFLD), and alcohol-associated liver disease (ALD).1

Other non-viral causes of HCC include iron overload syndromes, tobacco use, oral contraceptive use, aflatoxin exposure and betel quid chewing (defined as any chewing substance that contains areca nut). 3

Viral vs non-viral HCC presentations

Increasing evidence indicates that the causes of numerous HCC cases is multifaceted and can result from an interplay between viral, non-viral and environmental/ dietary factors. This article will focus on the main viral and non-viral causes. 3

Hepatitis B infection

Although chronic HBV infection contributes to ~50% of HCC cases, diagnosis and treatment rates are suboptimal. Chronic HBV infection can progress from an asymptomatic, persistently infected state to chronic hepatitis, cirrhosis, or as mentioned, HCC.1

Between 70% and 90% of HBV-related HCC cases occur in patients living with cirrhosis. However, it should be noted that even in the absence of cirrhosis, chronic HBV infection can lead to the development of HCC.4

Stages of liver disease in hepatitis

Factors contributing to HCC risk in both treated and untreated patients living with chronic HBV infection include demographic elements (such as male gender, advanced age, and African ancestry), viral factors (including high viral load, prolonged infection, and coinfection with HCV, HIV, or HDV), clinical aspects (particularly the presence of liver cirrhosis), and environmental exposures (such as aflatoxin, alcohol consumption, or tobacco use). 4

Curative treatments for HBV are still lacking, but the good news is that suppressive antiviral medications are effective in slowing disease progression.1

Mechanisms involved in progression to HCC in chronically infected HBV patients

The prognosis of HCC patients is poor compared with other GI tract tumours, with an estimated fiveyear survival rate of <20%

The development of HCC in patients living with chronic HBV involves multifaceted mechanisms. Various steps in the viral and hepatocyte life cycle, along with alterations in microenvironment homeostasis, contribute to tumorigenesis. Mutations in HBV genes, including pre-surface 1 and 2, polymerase, pre-core/core, and X protein, heighten HCC risk. 4

Proteogenomic analysis of HBV-related HCC identified mutated genes (tumour protein [TP] 53, catenin beta 1 [CTNNB1], axis inhibition protein 1, kelch-like erythroid cell-derived protein with cap’n’collar homology-associated protein 1, retinoblastoma 1), along with pyrroline-5-carboxylate reductase 2 and alcohol dehydrogenase 1A as prognostic biomarkers linked to metabolic reprogramming. 4

In the immune system and microenvironment of HBVrelated HCC, regulatory T-cells (TREG) and resident memory T-cells (TRM) play roles. TREG and TRM enrichment in the tumour microenvironment indicates immunosuppression and exhaustion, respectively. 4

Higher levels of tumour-infiltrating TREG are associated with poorer overall survival, while increased TRM correlate with improved survival. The expression of programmed cell death protein 1 (PD-1) on TREG and TRM suggests potential responsiveness to PD-1 inhibitors in HBV-related HCC. 3

Hepatitis C infection

HCV infection contributes ~18% to the global HCC burden. The predominant risk factors for the development of HCC in chronic HCV infection include concurrent liver disease, viral genotype, lifestyle factors (eg smoking, alcohol use and coffee ingestion) and comorbid obesity and diabetes.1,5

Coinfection with HBV and HIV significantly increases the risk of HCC in patients living with chronic HCV-infection. In HIV-HCV

coinfection, older age, cirrhosis, and low current CD4 cell count are associated with a higher incidence of HCC.1,5

Attaining a sustained virologic response through antiviral treatment has been shown to avert liver-related complications in patients living with cirrhosis linked to HCV infection.1

Mechanisms involved in progression to HCC in chronically infected HBV patients

HCV infection drives HCC development gradually, influenced by disease duration and viral genotype. Certain HCV genotypes, particularly genotype 3 and genotype 6, increase

NEPHROLOGY | Hepatocellular carcinoma

HCC risk. The carcinogenic process spans 20 to 40 years, mediated by viral-induced factors and host immunological responses. 5

HCV core proteins can induce lipogenesis and disrupt oxidative stress metabolism. Viral proteins impact cell signalling pathways, inhibiting tumour suppressors and activating growth-promoting pathways. 4

Host immune responses contribute through inflammation, inducing repeated cell cycles that accumulate mutations, especially in genes like telomerase reverse transcriptase, TP53, and CTNNB1, fostering HCC development. Oxidative stress from the virus and immune response contributes to hepatocyte mutations, culminating in HCC.4

Non-alcoholic liver disease

NAFLD is the most common underlying chronic liver disease in HCC patients awaiting transplantation. With an estimated 30% global prevalence, projected to reach 55.7% by 2040, NAFLD-related HCC incidence is increasing. Detection rates of HCC in patients living with NAFLD are low, leading to advanced-stage diagnoses and poorer survival.1

Mechanisms involved in progression to HCC in patients living with NAFLD

The progression of HCC in NAFLD is influenced by systemic factors, including obesity and insulin resistance, leading to systemic inflammation and activation of oncogenic pathways. 6

Increased hepatic lipid storage contributes to lipotoxicity, endoplasmic reticulum stress, and DNA damage, promoting oncogenesis.

Genetic polymorphisms, gender differences, and alterations in the gut microbiome also play roles, with men exhibiting a higher prevalence of NAFLD and HCC. 6

The main drivers of chronic liver diseases and cirrhosis include viral hepatitis (predominantly HBV and HCV subtypes)

Alcohol-associated liver disease

Alcohol contributes to 5% of global cancer burdens, and ALD-related HCC incidence is significant, especially among those with cirrhosis. Alcohol’s impact on mortality and decompensation in cirrhotic patients is dose-dependent.1

Factors such as genetic predisposition, age, gender, pre-existing liver disease, and daily alcohol consumption contribute to ALD progression, impacting the GI tract’s metabolism and systemic absorption of ethanol.7

Mechanisms involved in progression to HCC in patients living with ALD

The development of ALD requires excessive and chronic alcohol consumption. Although not a frequent cause, ALD remains a significant contributor to chronic liver disease including HCC.7

Specific single nucleotide polymorphisms in genes like patatin-like phospholipase domain-containing protein 3, transmembrane 6 superfamily member 2, and membrane-bound o-acyltransferase domain-containing 7 are linked to increased NAFLD progression and HCC risk.6

Epigenetic factors, such as non-coding RNAs and DNA methylation, contribute, with circulating micro-RNAs and long non-coding-RNAs showing promise as diagnostic biomarkers. 6

Dysbiosis in the gut microbiome is associated with NAFLD and HCC, suggesting therapeutic potential. Signalling pathways like interleukin-6, janus kinase, and signal transducer and activator of transcription (STAT), especially STAT-3, present potential therapeutic targets. 6

Causes of liver cancer (Hepatocellular carcinoma)

Alcohol metabolism primarily occurs in the liver, involving alcohol dehydrogenase and the microsomal ethanol-oxidising system.

Mitochondrial dysfunction, resulting from increased ethanol metabolisation, is critical in ALD onset and progression.7

Dysfunctional mitochondria undergo fragmentation, influencing liver injury through mitochondrial dynamics. ALD induces a leaky gut, altering the gut microbiota and promoting systemic endotoxemia.7

In ALD, toll-like receptor-4 activation perpetuates liver inflammation, impacting the gut microbiota. Changes in the gut microbiota, including altered bacterial diversity, contribute to early HCC development.7

ALD-related dysbiosis influences bile acid composition, potentially leading to cytotoxicity and carcinogenesis. Bile acids and cellular senescence play roles in HCC development.7

Modulating the gut microbiota, through non-absorbable antibiotics, probiotics, or faecal microbiota transplantation, shows promise in experimental studies for HCC management, although clinical standardisation is lacking.7

Conclusion

Liver cancer, primarily HCC, poses a significant global health challenge. Chronic liver diseases, driven by various factors like viral hepatitis, NAFLD, and ALD, contribute significantly to HCC development. Understanding the intricate mechanisms involved is crucial for advancing diagnostics and therapeutic strategies in mitigating this disease burden.

References are available on request. SF

ONLINE CPD: ONCOLOGY | Prostate cancer

This article was independently sourced by Specialist Forum.

Novel hormone agents: The new standard of care in mHSPCa

The prevalence of prostate cancer (PCa) in southern Africa has increased by ~60% across all ethnic groups over the last 15 years. Men of African descent are particularly affected, presenting with more advanced and higher-grade disease compared to other ethnic groups.

PCa is the fifth leading cause of morbidity worldwide. In 2020, 1.4 million men globally were diagnosed with PCa, resulting in 375 000 deaths. In South Africa, PCa represents 13% of cancer morbidity among men, with the incidence projected to increase to 2.9 million cases by 2040 due to ageing populations and improved life expectancy.

PCa risk increases with age, genetics, lifestyle, and other health conditions. Older men >79-years have a significantly higher risk at 59% compared to men <30-years, who have a 5% risk. Men of African descent face double the risk of those of European

descent. Lifestyle factors such as high consumption of red and processed meats, imbalanced vitamin D levels, obesity, and high alcohol intake are linked to increased PCa risk. Health conditions like metabolic syndrome, inflammatory bowel disease, gonorrhea, and HPV-16 infection also exacerbate PCa risk.

Screening guidelines in South Africa recommend starting PCa screening at age 50, or 45 for men of African descent or those with a family history of PCa or breast cancer, and at 40 for those with genetic predispositions. Screening is not advised for men >70-years or those with a life expectancy of <10-years. Prostate-specific

START XTANDI™ TO EXTEND SURVIVAL

EFFECTIVE TUMOUR CONTROL CAN’T WAIT

XTANDI™ - a novel hormone therapy with proven first-line efficacy indicated across mHSPC*1, high-risk nmCRPC**1 and asymptomatic/mildly symptomatic mCRPC1

antigen testing is the primary screening method, followed by further evaluation if needed.

Metastatic PCa

Treatment for metastatic PCa has evolved significantly. Androgen deprivation therapy remains foundational, but adding docetaxel and novel hormone agents like abiraterone and enzalutamide has improved survival outcomes. Clinical trials have shown that combination therapies enhance overall survival and delay disease progression. To access the article and quiz, go to https://www.medicalacademic.co.za/ courses/ SF

This CPD activity was made possible by Astellas. The content was independently sourced. nmCRPC**1 mHSPC*1

TO ACCESS YOUR LOCAL XTANDI™ WEBSITE, WITH CLINICAL TRIALS, PROSTATE CANCER GUIDELINES, PATIENT INFORMATION AND ACCESS SUPPORT, SCAN HERE.

*High-risk = a minimum of three rising PSA values at an interval of at least 1 week apart, a baseline PSA level of 2 ng/mL or greater, and a PSA doubling time of 10 months or less. **nmCRPC = No previous or current evidence of metastatic disease as assessed by CT or MRI for soft-tissue disease and by whole-body radionuclide bone scanning. mHSPC = metastatic hormone-sensitive prostate cancer; nmCRPC = non-metastatic castration-resistant prostate cancer; mCRPC = metastatic castration-resistant prostate cancer; PSA = prostate-specific antigen; CT = computed tomography; MRI = magnetic resonance imaging.

Reference: 1. XTANDI™ Professional Information. Astellas Pharma (Pty) Ltd. 31 July 2024. For full prescribing information, refer to the Professional Information approved by the Regulatory Authority. South Africa: XTANDI™ 40 mg soft capsules. Reg. No.: 48/26/0404. Each soft capsule contains 40 mg of enzalutamide. Applicant: Astellas Pharma (Pty) Ltd, Reg No. 2002/024956/07, 7 Mirage Road, Bedfordview, South Africa, 2007. Tel: 011 615 9433 Fax: 011 615 9427. Drug safety email: drugsafety.za@astellas.com or Fax: 086 624 2947. Date of Preparation: August 2024. MAT-ZA-XTD-2024-00046.

Link between ADHD and ODD

Attention deficit hyperactivity disorder (ADHD) is recognised as the most prevalent neurodevelopmental disorder, with onset typically in childhood and frequently persisting into adulthood. Contrary to outdated beliefs, individuals do not outgrow ADHD, instead, they may learn to manage their symptoms more effectively over time. The disorder has significant implications for social, academic, and occupational functioning, underscoring the necessity for proper management.

ADHD is divided into three subtypes: Combined, predominantly hyperactiveimpulsive, and predominantly inattentive, the latter often referred to as attention deficit disorder.

The global prevalence of ADHD in children and adolescents can reach up to 7%, with males being more commonly diagnosed at a ratio of 3:1 compared to females. Interestingly, females are more likely to present with the inattentive type, which often leads to later diagnoses.

The root causes of ADHD are multifactorial, involving both biological and environmental factors. Studies indicate that ADHD is highly hereditary, with a heritability rate of 76%. Other risk factors include low birth weight, prenatal exposure to smoking and alcohol, poor diet, child abuse, neglect, and lead exposure.

Neurobiologically, ADHD is linked to dysregulation of dopamine and norepinephrine, alongside structural and functional changes in the brain, particularly within the prefrontal cortex, basal ganglia, reticular activating system, and limbic system.

Oppositional defiant disorder (ODD) is another disorder frequently associated with ADHD. ODD is characterised by a persistent pattern of angry or irritable mood, argumentative or defiant behaviour, and vindictiveness lasting at least six months. This disorder primarily affects children and

adolescents and is more common in males. The prevalence of ODD is approximately 3.3%, with a higher incidence in boys.

The connection between ADHD and ODD is significant, as they often co-occur. Research indicates that up to 50% of children with ADHD also meet the criteria for ODD. This comorbidity arises due to the overlap in symptoms, such as impulsivity and difficulties with emotional regulation. The presence of both disorders can exacerbate the severity of symptoms and complicate treatment.

ADHD can serve as a precursor to ODD, with untreated ADHD often leading to the development of additional behavioural issues, such as ODD. The overlap between these conditions can result in misdiagnosis, complicating the management of each disorder. Thus, recognising and addressing ADHD early is crucial in preventing the development of ODD and other associated conditions.

The management of ADHD and ODD requires a comprehensive approach. For ADHD, stimulant medications like methylphenidate and non-stimulant options like atomoxetine are commonly prescribed. Behavioural interventions focus on improving organisational skills, impulse control, and social interactions.

For ODD, behavioural therapy is crucial, aiming to enhance communication, problem-solving skills, and emotional

regulation. Parent training programmes, such as parent-child interaction therapy, have shown effectiveness in managing ODD symptoms by promoting positive parenting techniques and consistent discipline.

In conclusion, the link between ADHD and ODD is well-established, with ADHD often preceding and exacerbating the symptoms of ODD. Effective management of ADHD can help prevent the development of ODD, emphasising the importance of early diagnosis and intervention. By addressing both conditions simultaneously through a multimodal treatment approach, individuals with ADHD and ODD can achieve better outcomes in social, academic, and occupational settings.

To watch a replay of the webinar, click here or scan the QR code.

These webinars are accredited for one (1) CPD point each. Once you have watched the replays, send an e-mail to john.woodford@ newmedia.co.za and request to have your CPD point allocated to your profile on the HPCSA database. Include the webinar name and your HPCSA number in your e-mail.

Dr Clementine Chawane

(first episode or multiple episodes/relapse)2

THE

with aggression, psychosis, resistance to care or restlessness (in combination with haloperidol)2

ACCORD DIFFERENCE IN MENTAL HEALTH

References: 1. Rispacor 0, 5, 1, 2, and 3 (tablets) approved professional information, October 2009. 2. The South African Society of Psychiatrists (SASOP) Treatment Guidelines for Psychiatric Disorders (Part 2). SAJP 2013;19(3):128-196. 3. Sajatovic M, Madhusoodanan S, Fuller MA. Risperidone in the treatment of bipolar mania. Neuropsychiatric Disease and Treatment 2006;2(2):127–138. 4. Bishop JR, Pavuluri MN. Review of risperidone for the treatment of pediatric and adolescent bipolar disorder and schizophrenia. Neuropsychiatric Disease and Treatment 2008;4(1):55–68. 5. Khan S, et al. Current pharmacotherapy options for conduct disorders in adolescents and children. Expert Opin Pharmacother. 2019;20:5,571-583. DOI: 10.1080/14656566.2018.1561862. 6. Umbricht D, et al. Risperidone: Efficacy and safety. Schiz Bull 1995;21(4):593-606.

Acute mania in bipolar disorder2

Schizophrenia

Dementia

Clear skin solutions, effective acne treatments and strategies

AAcne is a chronic inflammatory skin disease that affects the pilosebaceous follicle, comprising hair follicles and sebaceous glands. It primarily manifests on the face and upper back, where sebaceous glands are most concentrated.

bout 80% of adolescents (between 13- and 18-years) experience acne, making it one of the most common dermatological conditions. Acne is multifactorial, with four primary factors driving its development:

1 Hyperkeratinisation and comedo formation: The process begins with hyperkeratinisation, where hair follicles become clogged with sebum and keratinocytes, leading to the formation of comedones, the initial lesions of acne. Comedones can be either open (blackheads) or closed (whiteheads). If untreated, these can evolve into inflammatory lesions such as papules, pustules, nodules, and cysts.

2

Bacterial proliferation: Cutibacterium acnes, a normal skin bacterium, thrives in the sebum-rich environment created by clogged follicles. This bacterial proliferation triggers an immune response, leading to inflammation, redness, and swelling commonly associated with acne lesions.

3 Sebaceous hypersecretion:

Sebaceous glands in individuals with acne- prone skin tend to overproduce sebum, contributing to excess oiliness on the skin’s surface. This overproduction of sebum is often linked to hormonal changes, particularly during puberty, menstruation, or pregnancy, which stimulate androgen release.

4

Inflammatory mediators: The final factor involves the release of inflammatory mediators in response

to bacterial colonisation. This inflammation can result in varying intensities of acne, from mild papules and pustules to severe nodules and cysts, potentially leading to permanent scarring if not treated early. Acne can be categorised into noninflammatory and inflammatory lesions. Non-inflammatory lesions include comedones, while inflammatory lesions result from bacterial proliferation and include papules, pustules, nodules, and cysts. Severe inflammatory lesions can lead to permanent scarring, emphasising the importance of early intervention and proper treatment.

Common triggers of acne include hormonal changes, inadequate skin care products, certain foods with high glycemic indices, and stress, which can exacerbate sebum production. Acne severity ranges from mild, with comedonal and papulopustular acne, to severe, with nodular, cystic, and conglobate acne. Identifying the severity is crucial for tailoring appropriate treatment plans.

Acne can have significant psychological impacts, particularly during adolescence, leading to issues like anxiety, depression, social withdrawal, and even suicidal ideation. Therefore, effective acne management is vital not only for physical health but also for mental well-being.

Treatment options for acne vary depending on the severity. For mild cases, topical treatments like retinoids, benzoyl peroxide, and antibacterials are commonly used. Systemic treatments, such as oral antibiotics or isotretinoin, are reserved

for more severe cases. Isotretinoin, in particular, is highly effective, addressing all aspects of acne pathogenesis, including sebum production. However, it requires careful monitoring due to potential side effects, such as dry skin, liver function abnormalities, and teratogenic risks.

In managing acne, it is essential to regulate sebum production, prevent follicular obstruction, control bacterial proliferation, reduce inflammation, and prevent scarring. Patients should be educated on the importance of a consistent skincare routine, including the use of moisturisers and sunscreens, while avoiding the use of topical steroids and oily cosmetics.

Overall, while acne is common and often considered a normal part of adolescence, its potential to cause lasting physical and emotional scars underscores the importance of early and effective treatment.

To watch a replay of the webinar, click here or scan the QR code.

This webinar is accredited for one (1) CPD point. Once you have watched the replay, send an e-mail to john.woodford@ newmedia.co.za and request to have your CPD point allocated to your profile on the HPCSA database. Please include the webinar name and your HPCSA number in your e-mail.

Dr Lushen Pillay

This article was independently sourced by Specialist Forum.

Managing atopic dermatitis comorbidities

Atopic dermatitis (AD) is a chronic, systemic, immune-mediated type 2 inflammatory disease characterised by intense pruritus and recurrent eczematous lesions. This condition significantly impacts patients’ quality of life (QoL) and daily activities, with the burden increasing alongside disease severity and the presence of coexisting type 2 inflammatory illnesses.

The aetiology of AD is multifactorial, involving genetic, environmental, immune, and microbiome factors. A key driver of AD is type 2 inflammation, which leads to epithelial barrier dysfunction. This dysfunction allows water loss and the penetration of irritants and allergens, triggering inflammation via the Th2 pathway.

Dendritic cell activation and the release of interleukins 4 and 13 further drive type 2 inflammation, resulting in lesion formation, pruritus, and bacterial colonisation. This can lead to infections and hospitalisation.

AD affects ~4%-5% of the global population, with a prevalence of 4.4% in the European Union and 8.3% among children aged 13- to 14-years in Cape Town. The lifetime prevalence is 15%-30% in children and 2%-10% in adults, with incidence rates increasing two to three times since the 1970s. AD typically begins before the age of five, with risk factors for persistence into adulthood including later onset, greater severity, and a family history of atopy. AD lesions vary in appearance and

distribution based on patient age. In infants, lesions commonly affect the face and extensor surfaces. In children, flexural areas are more commonly involved, while adolescents often experience lesions on the wrists, ankles, eyelids, and scalp.

The disease’s activity varies, and flares are not always seasonal. Pruritus is a major criterion for diagnosis, along with a history of flexural dermatitis, visible flexural dermatitis, history of dry skin, personal or family history of atopic disease, and onset under two years of age.

AD significantly impacts patients’ quality of life, particularly in children, causing symptoms like itch, sleep disturbance, and increased asthma. Adults with AD often experience mental health disorders such as anxiety, depression, and suicidal ideations.

The disease also leads to impaired daily activities, reduced productivity, loss of work or school days, and sleep disturbances. Financially, AD is burdensome, with high annual costs and increased infections. Treatment aims to balance efficacy, side effects, and cost. Initial steps include avoiding irritants and using emollients.

Dr Lushen Pillay

For active disease, topical corticosteroids and calcineurin inhibitors are recommended. If these fail, phototherapy and systemic immunosuppressants like methotrexate and cyclosporine are used.

Biologics and Janus kinase inhibitors are options if traditional treatments fail. Early treatment is crucial to avoid comorbidities such as cardiovascular, respiratory, and autoimmune diseases.

To watch a replay of the webinar, click here or scan the QR code.

This webinar is accredited for one (1) CPD point. Once you have watched the replay, send an e-mail to john.woodford@ newmedia.co.za and request to have your CPD point allocated to your profile on the HPCSA database. Include the webinar name and your HPCSA number in your e-mail. SF

Significantly improves and protects against the signs and symptoms of dry skin disorders 4,5,6

Contains optimal skin-identical lipids (ceramides, cholesterol and free fatty acids) for accelerated barrier repair. 2

Effectively repairs skin barrier function in less than 6 hours. 7

Significantly reduces transepidermal water loss after 24 hours. 8

48-Hour moisturisation and maintenance of the skin barrier with a single, small amount application.8*

* Dermatologist confirmed.8

30 YEARS OF REVOLUTIONARY THERAPY DESIGNED TO HELP TREAT ACUTE AND CHRONIC DRY SKIN DISORDERS. 1,9,10

References: 1. SBR PROTECT® package leaflet. July 2021. 2. SBR REPAIR® package leaflet. July 2021. 3. Adcock Ingram Data on File. 4. Tsiskarishvili NV, Katsitadze EG, MSh E, Tsiskarishvili NI. Therapeutic efficacy of locobase cream in the treatment of atopic dermatitis. Georgian Medical News. 2009 Dec 1(177):55-9. 5. Kynemund L, Jemec GB, Wulf HC. Moisturisers for Psoriatic Skin–Do Gross Morphological Differences Matter?. Skin Pharmacology and Physiology. 2001;14(1):20-6. 16. Berardesca E, Barbareschi M, Veraldi S, Pimpinelli N. Evaluation of efficacy of a skin lipid mixture in patients with irritant contact dermatitis, allergic contact dermatitis or atopic dermatitis: a multicenter study Contact Dermatitis. 2001 Nov;45(5):280-5. 7. Mortz CG, Andersen KE, Halkier‐Sorensen L. The efficacy of different moisturizers on barrier recovery in hairless mice evaluated by non‐invasive bioengineering methods: A model to select the potentially most effective product. Contact Dermatitis. 1997 Jun;36(6):297-301. 8. Test Report 21 39 00123, June 2021, Use test assessment of the efficacy skin moisture and transepidermal water loss. 9. SBR-LIPOCREAM™ package leaflet. July 2006. 10. Halkier-Søsensen, L and Thesirup-Pedersen, K. (1993), The efficacy of a moisturizer (Locobase) among cleaners and kitchen assistants during everyday exposure to water and detergents. Contact Dermatitis, 29:266-271. https://doi.org/10.1111/j.1600-0536.1993.tb03563.x.

Under licence from Karo Pharma Stockholm, Sweden. For full prescribing information, refer to the professional information approved by the Medicines Regulatory Authority. Adcock Ingram Healthcare (Pty) Ltd. Co. Reg. No. 2007/019928/07. Private Bag X69, Bryanston, 2021, South Africa. Customer Care: 0860 ADCOCK / 232625. www.adcock.com. 2022112110243341 July 2023 https://www.facebook.com/SBRsouthafrica/ https://www.karohealthcare.com/

Advanced treatment options in psoriasis

Psoriasis is a chronic inflammatory skin disorder characterised by the overproduction of skin cells, leading to red, thick, and scaly plaques. These plaques are often covered with a white, silvery scale and can appear on various parts of the body, including the scalp, elbows, knees, and trunk.

The condition results from a complex interaction of genetic, environmental, and immune system factors. It significantly impacts quality of life, contributing to increased mortality rates and a shorter lifespan.

Plaque psoriasis, the most prevalent form, affects ~85% of patients. Common symptoms include scaling (94% of patients), itching (79%), redness, skin tightness, and discomfort, all of which can greatly disrupt daily activities.

Psoriasis has a global prevalence ranging from 0.3% to 2.5%, with a higher incidence in South Africa, where between 7%-8% of the population may be affected.

The disease typically presents in two peaks: Early onset between 16- to 22years, often linked with a severe form and family history, and late onset between 57to 60-years, usually milder and less likely to have familial connections.

Psoriasis is also associated with various comorbidities, including metabolic syndrome, diabetes, cardiovascular diseases, psoriatic arthritis, and mental health issues such as depression and anxiety. These comorbidities contribute to the reduced life expectancy in psoriasis patients.

Diagnosing psoriasis can be complex

due to its similarity to other dermatological conditions such as fungal infections, eczema, and skin cancers. A biopsy may be required to differentiate it from conditions like cutaneous T-cell lymphoma or mycosis fungoides.

Management of psoriasis involves a tailored approach based on disease severity, affected areas, and patient quality of life. Treatment options range from topical therapies for mild cases to systemic treatments and biologics for moderate to severe cases.

The latest advancements include biologics, particularly interleukin inhibitors, which offer near-complete skin clearance and represent a significant improvement in psoriasis management. These therapies have heightened patient expectations, making them less willing to revert to previous treatments.

Effective psoriasis management requires a holistic approach, addressing both medical and psychological aspects of the disease. Long-term strategies often involve combination therapies to minimise toxicity and enhance outcomes.

Regular monitoring is essential, especially with drugs like methotrexate, which require frequent liver function tests. Lifestyle factors such as stress, smoking, and alcohol

consumption can exacerbate the condition, necessitating careful management.

For mild to moderate psoriasis, topical therapies remain the cornerstone of treatment. Emollients are crucial for symptom relief and enhancing the effectiveness of other treatments.

A combination of vitamin D analogs and corticosteroids is effective for longterm maintenance. For more severe cases, treatments like UVB phototherapy and systemic agents are used, with biologics offering promising results for those with moderate to severe forms of the disease.

To watch a replay of the webinar, click here or scan the QR code.

The webinar is accredited for one (1) ethics point. Once you have watched the replay, send an e-mail to john.woodford@ newmedia.co.za and request to have your point allocated to your profile on the HPCSA database. Include the webinar name and your HPCSA number in your e-mail. SF

Dr Lushen Pillay

calcipotriol/betamethasone dipropionate

DESIGNED

UNCOVER THE LIFE CHANGING TREATMENT FOR PSORIASIS FROM THE FIRST WEEK 1-3

References: 1. Van de Kerkhof PCM. The impact of a two-compound product containing calcipotriol and betamethasone dipropionate (Daivobet®/Dovobet®) on the quality of life in patients with psoriasis vulgaris: a randomised controlled trial. 10.1111/j. 1365-2133.2004.06134.x. 2. Kaufmann R, Bibby AJ, Bissonnette R, Cambazard F, Chu AC, Decroix J, et al. A New Calcipotriol/Betamethasone Dipropionate Formulation (Daivobet™) Is an Effective Once-Daily Treatment for Psoriasis vulgaris. 10.1159/000066440. 3. Saraceno R, Gramiccia T, Frascione P, Chimenti S. Calcipotriene/ betamethasone in the treatment of psoriasis: a review article. Expert Opin Pharmacother 2009;10(14): 2357-2365. 4. Kragballe K, Austad J, Barnes L, Bibby A, de la Brassinne M, Cambazard F, Results of a 52-Week, Randomised, Double-Blind, Safety Study of a Calcipotriol/ Betamethasone Dipropionate Two-Compound Product (Daivobet®/Dovobet®/Taclonex®) in the Treatment of Psoriasis Vulgaris. Dermatol 2006;213:319-326. DOl: 10.1159/000096069. 5. Luger TA, Cambazard F, Larsen FG, Bourcier M, Gupta G, Clonier F, et al. A Study of the Safety and Efficacy of Calcipotriol and Betamethasone Dipropionate Scalp Formulation in the Long-Term Management of Scalp Psoriasis. Dermatol 2008;217:321–328. DOI: 10.1159/000155642. 6. Claréus BW, Houwing R, Sindrup JH, Wigchert S. The DESIRE study – psoriasis patients’ satisfaction with topical treatment using a fixed combination of calcipotriol and betamethasone dipropionate in daily clinical practice. Eur J Dermatol 2009;19(6):581-5. doi: 10.1684/ejd.2009.0767. 7. Dovobet® (Ointment) approved package insert, October 2013. 8. Dovobet® Gel prescribing information, March 2019.

27 11 635 0000. www.adcock.com. 17554N. 2021071310137595.

Selecting treatment for PCa patients based on affordability vs efficacy

IDr Diane Pillay

Prostate cancer (PCa), the second most common cancer in men worldwide and the fifth leading cause of cancer-related deaths, presents significant ethical challenges in its management.

n 2020, there were ~1.4 million new cases and 375 000 deaths globally. The projected figures for 2040 suggest an increase to around 2.3 million cases and at least 740 000 deaths, driven by population growth and ageing.

The disparity in incidence and mortality rates between developed and developing regions, such as Southern Africa, highlights ethical concerns related to resource allocation, screening, and treatment.

The high incidence of PCa in developed countries, partly due to widespread PSA screening, contrasts with lower mortality rates compared to regions like Southern Africa, where socioeconomic, sociocultural, and genetic factors contribute to higher death rates. In Southern Africa, PCa accounts for 13% of cancer-related deaths among men, reflecting significant disparities in healthcare access and quality.

The ethical dilemmas in PCa care stem from balancing patient needs with available resources. Medical ethics, which has evolved since the 1970s but has roots in earlier philosophical traditions, guides these decisions. The principles of medical ethics include:

1 Respect for autonomy: This principle underscores the importance of honoring a patient’s right to make informed decisions about their care. Informed consent is a key aspect, ensuring that patients understand their options and the potential outcomes of their choices.

2 Beneficence: Healthcare professionals are obligated to act in the best interest of patients, aiming to provide treatments that benefit their health and well-being.

3 Non-maleficence: This principle, often summarised as ‘do no harm’, directs healthcare providers to avoid

causing harm and to minimise risks associated with treatment.

4 Justice: Justice requires the fair distribution of healthcare resources, addressing the need for equitable access to care, particularly in resource-limited settings. These principles are interrelated and must be balanced, as they do not operate hierarchically. Ethical decision-making involves navigating conflicts where one principle may take precedence over others depending on the context.

Ethical theories provide additional frameworks for understanding these principles:

_ Deontology emphasises adherence to rules and duties regardless of the outcomes. In the context of PCa, this theory highlights the moral obligations healthcare providers have towards their patients.

_ Utilitarianism focuses on actions that maximise overall benefit while minimising harm. This approach is often used in healthcare policy to evaluate costeffectiveness and resource allocation. Balancing affordability and efficacy are critical issues in PCa care. The practice of medical paternalism, where doctors make decisions based on what they believe is in the patient’s best interest, can sometimes undermine patient autonomy. While traditional paternalism has been criticised for reinforcing power imbalances, ‘soft paternalism’ offers a middle ground by gently guiding patients while respecting their autonomy.

The principle of double effect also plays a role in cancer care, where treatments like chemotherapy aim to improve patient outcomes but may also cause significant side effects. Similarly, palliative care practices, such as administering morphine,

can alleviate pain but may accelerate death, demonstrating the complexity of balancing positive and negative outcomes.

In South Africa, the cancer burden has increased as deaths from infectious diseases have decreased. However, inadequate funding for non-communicable diseases like cancer exacerbates treatment disparities, creating a two-tiered system with limited access to advanced therapies for many patients. The ethical challenge lies in addressing these disparities while managing the high costs of new treatments. Cancer screening, particularly for PCa, raises ethical questions about overdiagnosis and unnecessary treatments. In regions where PCa disproportionately affects certain populations, targeted screening strategies could help address disparities and improve outcomes.

As advances in cancer treatment continue, healthcare professionals must navigate the ethical complexities of balancing efficacy with affordability. The principles of medical ethics offer a crucial framework for making decisions that prioritise patient welfare while addressing resource limitations.

To watch a replay of the webinar, click here or scan the QR code.

The webinar is accredited for one (1) ethics point. Once you have watched the replay, send an e-mail to john.woodford@ newmedia.co.za and request to have your CPD point allocated to your profile on the HPCSA database. Include the webinar name and your HPCSA number in your e-mail.

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Ulcerative colitis – what the GP needs to know

Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) primarily affecting the colon and rectum. The disease is characterised by symptoms such as frequent diarrhoea mixed with blood and mucus, abdominal pain, and weight loss. The goal of diagnosis is to differentiate UC from other conditions that present similarly, such as Crohn’s disease, infectious colitis, or malignancy.

Diagnosis begins with a thorough history and physical examination. Key factors include the duration, frequency, and characteristics of diarrhea, as well as associated symptoms like weight loss or fever.

A history of recent antibiotic use could indicate a Clostridium difficile infection, which might mimic UC symptoms. An evaluation of stool characteristics, including presence of blood or mucus, and any nocturnal diarrhea is crucial.

A family history of IBD or colorectal cancer, alongside other systemic symptoms like joint pain or skin lesions, can provide additional diagnostic clues.

The physical examination might reveal anaemia, abdominal tenderness, or perianal abnormalities. Digital rectal examination, while not always pleasant, can sometimes uncover hidden pathologies. Extra-intestinal manifestations such as eye inflammation, skin lesions, or joint pain can also suggest underlying IBD.

Diagnosing UC involves ruling out other conditions with similar presentations. Tests such as faecal calprotectin are useful to differentiate IBD from irritable bowel syndrome, as elevated levels indicate intestinal inflammation.

Endoscopy, including colonoscopy, is essential for visualising the colon and rectum, assessing the extent of inflammation, and identifying mucosal changes characteristic of UC. The Mayo score is used to classify disease

severity from mild to severe based on endoscopic findings.

The goals of treatment are to control inflammation, induce and maintain remission, and improve the patient’s quality of life while minimising side effects. Long-term management often requires a multidisciplinary approach involving gastroenterologists, dietitians, and other specialists to address the various aspects of the disease and its impact on daily life.

The treatment of UC aims to induce and maintain remission while preventing complications. The management approach is tailored to the disease severity and the patient’s response to previous treatments.

Initial treatment often involves 5-aminosalicylic acid compounds, which are effective for inducing and maintaining remission in mild to moderate cases. These can be administered orally or rectally depending on the extent of the disease.

For moderate to severe cases, corticosteroids (CS) such as prednisone or budesonide are used to quickly induce remission. However, due to potential side effects like weight gain, hypertension, and osteoporosis, CS are not suitable for longterm use. Their use is typically limited to short-term management and bridging to other therapies.

Immunomodulators, including azathioprine and 6-mercaptopurine, are effective for maintaining remission and reducing steroid dependency, but they take several weeks to become effective and

Dr Nazeer Ahmed Ismail Chopdat

require regular monitoring due to potential side effects. Methotrexate may be used in some cases, though its application is less common.

Biologics such as anti-TNF agents (eg infliximab, adalimumab) offer targeted therapy by addressing specific immune responses involved in UC. These are particularly useful in severe cases or when patients are unresponsive to conventional therapies. Newer options like integrin inhibitors and small molecules are emerging, offering additional choices for managing UC.

In summary, managing UC effectively involves accurate diagnosis, targeted therapy, and regular monitoring to adjust treatment as needed and address potential complications.

To watch a replay of the webinar, click here or scan the QR code.

The webinar is accredited for one (1) CPD point. Once you have watched the replays, send an e-mail to john.woodford@ newmedia.co.za and request to have your CPD point allocated to your profile on the HPCSA database. Include the webinar name and your HPCSA number in your e-mail.

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References: 1. South African Medicine Price Registry. Database of Medicine Prices, 01 November 2023 [online]. [cited November 2023]; Available from URL: http://www.mpr.gov.za/.

2. Monthly Index of Medical Specialities. September 2023;63(No. 8):185-191. 3. Metz DC, Howden CW, Perez MC, et al. Clinical trial: dexlansoprazole MR, a proton pump inhibitor with dual delayed-release technology, effectively controls symptoms and prevents relapse in patients with healed erosive oesophagitis. Aliment Pharmacol Ther. 2009;29(7):742-54. doi: 10.1111/j.1365-2036.2009.03954.x. 4. Gąsiorowska A. The role of pH in symptomatic relief and effective treatment of gastroesophageal reflux disease. Prz Gastroenterol. 2017;12(4):244249. doi: 10.5114/pg.2017.72097. 5. Frye JW, Peura DA. Managing gastroesophageal reflux disease - comparative efficacy and outcomes of dexlansoprazole MR. Ther Clin Risk Manag 2015;11:1649-56. doi: 10.2147/TCRM.S66680. 6. Dexilant Professional Information. Takeda (Pty) Ltd, South Africa; August 2021. 7. Sharma P, Shaheen NJ, Perez MC, et al. Clinical trials: healing of erosive oesophagitis with dexlansoprazole MR, a proton pump inhibitor with a novel dual delayed-release formulation--results from two randomized controlled studies. Aliment Pharmacol Ther. 2009;29(7):731-41. doi: 10.1111/j.1365-2036.2009.03933.x. 8. Fass R, Chey WD, Zakko SF, et al. Clinical trial: the effects of the proton pump inhibitor dexlansoprazole MR on daytime and nighttime heartburn in patients with non-erosive reflux disease. Aliment Pharmacol Ther. 2009;29(12):1261-72. doi: 10.1111/j.1365-2036.2009.04013.x.

only dexlansoprazole available in South Africa. DDR: dual delayed-release; PPI: Proton pump inhibitor; QoL: quality of life. S4 DEXILANT 30 mg modified-release capsules, Reg. No.