Specialist Forum June 2024

No.1 in South Africa1 Tadalafil *

Special moments should be spontaneous and not hampered by timing or finances

Keeps on working for up to 36 hours Gets to work within 16 minutes

Up to 46 % cost saving vs. the originator and 32 % vs. the clone 4

Daily CYFIL allows continuous PDE-5 inhibition for men whose sexual satisfaction is impaired by planning and timing of treatment5

20 mg CYFIL gets to work after just 16 minutes, and lasts up to 36 hours with a single dose2,3

May be taken any time of the day6

Intercourse is possible again the next day6

Accessible and affordable to more South African men.7

ACCORD – QUALITY PRODUCTS MADE ACCESSIBLE AND AFFORDABLE TO MORE SOUTH AFRICANS

*Number 1 dispensed tadalafil molecule

References: 1. Based on internal analysis by Accord Healthcare using data from the following source: IQVIA Dispensed Data for the period MAT/01/2024, Script Lines, ATC3 G04B (Tadalafil-containing brands only) reflecting estimates of real-world activity. Copyright IQVIA. All rights reserved. 2. CYFIL (Film coated tablet) prescribing information, March 2021. 3. Levine SB. Erectile Dysfunction: Why drug therapy isn’t always enough. Cleve Clin J Med 2003;70(3):241- 246. 4. Accord data on file. 5. Wrishko R, Sorsaburu S, Wong D, Strawbridge A, McGill J. Safety, efficacy, and pharmacokinetic overview of low-dose daily administration of tadalafil. J Sex Med 2009;6:2039-48. DOI: 10.1111/j.1743-6109.2009.01301.x. 6. Tolrà JR, Campaña JMC, Ciutat LF, Miranda EF. Prospective, randomized, open-label, fixed-dose, crossover study to establish preference of patients with erectile dysfunction after taking three PDE-5 inhibitors. J Sex Med 2006;3:901- 909. DOI: 10.1111/j.1743-6109.2006.00297.x. 7. Accord Data on File.

S4 CYFIL 5 (film-coated tablet). Each 5 mg film-coated tablet contains 5 mg tadalafil and 91,572 mg lactose (as monohydrate). Reg No.: 50/7.1.5/0772. S4 CYFIL 20 (film-coated tablet). Each 20 mg film-coated tablet contains 20 mg tadalafil and 367,584 mg lactose (as monohydrate). Reg No.: 50/7.1.5/0773. For full prescribing information please refer to the professional information approved by the Regulatory Authority (SAHPRA). Accord Healthcare (Pty) Ltd. Reg. No.: 2004/011257/07. Tel: +27 11 234 5701/2/3. Building 31, Woodlands Office Park, 20 Woodlands Drive, Woodmead, 2191, Gauteng, SOUTH AFRICA. Postnet Suite 182, Private Bag X51, Rivonia, 2128. Email: medinfo@accordhealth.co.za. CYF/002/MAR24/AD.

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Winter’s health quandaries: Insights on cardiovascular diseases and more 6 INDUSTRY NEWS

New FDC therapy enhances AR symptoms and QoL in paediatric patients 9 ALLERGOLOGY

Online CPD: Enhancing paediatric allergic rhinitis care: The role of fixed-dose combination therapy

Finding relief when you can’t hold it in

DISEASES

Changing the trajectory of hep C infections in SA

Online CPD: Revolutionising HIV treatment in South Africa: The advantages of switching to TLD

Online CPD: One-size treatment approach to HIV does not fit all

Women’s teen weight battles may lead to later strokes 15 Is it normal for the heart to skip a beat and flutter? 18 Lifestyle changes key to managing hypertension 19 Online CPD: Is twice-daily dosing the key to unlocking optimal anticoagulation benefits?

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CPD: Rethinking the necessity of three-drug ART

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Winter has finally arrived in South Africa, bringing with it colder temperatures and shorter days. In this issue of Specialist Forum, we delve into key aspects of cardiovascular disease (CVD) management, focusing on atrial fibrillation (AFib) and heart failure (HF), premature ventricular contractions (PVCs), and hypertension.

CVDs pose a significant threat to public health worldwide, and understanding their mechanisms and management is paramount. AFib, the most common sustained cardiac arrhythmia, presents challenges in diagnosis and treatment. HF, a complex syndrome affecting

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Winter’s health quandaries Insights on cardiovascular diseases and more BRIDGES BUILDING

millions globally, requires comprehensive management strategies to improve patient outcomes, especially during the colder months when exacerbations may be more prevalent.

PVCs are often viewed as benign but can indicate underlying heart conditions, including the risk of sudden cardiac death. Recognising the significance of PVCs and implementing appropriate monitoring and intervention strategies is crucial, particularly in vulnerable populations.

Hypertension, a leading risk factor for CVD, requires diligent management, especially during winter when cold weather and reduced physical activity can exacerbate blood pressure fluctuations. Understanding the nuances of hypertension management in winter conditions is essential for optimising patient care and reducing CV risks.

We also provide updates on the latest recommendations for managing hepatitis C, a condition affecting an estimated 50 million individuals worldwide.

This issue offers valuable opportunities to earn CPD points. Earn 13 CPD points by accessing and completing our online quizzes, which cover topics such as HIV, AFib, and allergic rhinitis.

As healthcare professionals, it is our responsibility to stay vigilant and proactive in addressing cardiovascular health, particularly during the challenging winter season. By staying informed, implementing evidencebased practices, and prioritising patient care, we can make significant strides in reducing the burden of cardiovascular disease and improving patient outcomes.

We hope you find this issue of Specialist Forum informative and enlightening.

Warm regards, René Bosman

New FDC therapy enhances QoL in paediatric patients

Viatris recently announced the launch of their new fixed-dose combination (FDC) azelastine/fluticasone nasal spray for the treatment of moderate-to-severe seasonal and perennial allergic rhinitis (AR) in adults if the use of either intranasal antihistamines (INAH) or corticosteroids (CS) alone are not considered sufficient. This combination is also approved for the treatment seasonal AR in paediatric patients ≥6-years.1

AR is a chronic inflammatory disorder, characterised by an immunoglobulin E-mediated (IgE) inflammatory response triggered by allergen exposure in sensitised individuals. AR affects the nasal mucosa, causing episodes of repeated sneezing, rhinorrhoea and nasal congestion, often accompanied by itching of the eyes, nose and palate. AR is classified as seasonal or perennial, intermittent, or persistent based on symptom duration and frequency. 2,3,4

According to McDonald and De Waal, AR is often misdiagnosed as viral rhinosinusitis or upper respiratory tract infections (URTIs)

in paediatric patients. Untreated AR can lead to serious complications in this patient population including otitis media, recurrent sinusitis and sleep apnoea. In children living with comorbid asthma, AR can lead to poorly controlled symptoms and unnecessary prescriptions for antibiotics and oral CS. 4,5

Allergen triggers can be identified using skin-prick testing and serum IgE-measurement – but this should be performed early. However, noted McDonald and De Waal, in certain emerging AR phenotypes such as local AR, these procedures may have negative results

and a nasal allergen challenge should be performed. 4

Impact of AR on paediatric patients

According to McDonald and De Waal, the prevalence of AR in young paediatric patients is unknown. However, AR symptoms can present in children from as young as 24-months, and as mentioned, are often misdiagnosed. Some experts, do however, report an increase in AR prevalence of around 2% per year of age. 5 AR has a profound impact on the quality of life (QoL) of paediatric patients as well as their caregivers. A study by Blaiss

et al showed that AR negatively impacts several aspects on day-to-day living such as functioning, sleep, absenteeism, school productivity and academic performance. 6

Meltzer et al found that adolescents living with AR have high rates of somatisation, anxiety and depression, less resistance to stressful situations, and exhibit more hostility, impulsivity and rapid changes in interest. Parental assessment of the impact of AR on the day-to-day lives of paediatric patients living with AR indicates that AR makes their child unhappy, upset, angry and embarrassed.7

A more recent study by Bosnic-Anticevich et al showed that paediatric patients living with AR have a worse overall health status, fewer days being happy, more days of poor physical and emotional health compared with their counterparts not affected by the disease. AR negatively impacts schoolwork, sleep and other activities. Children accomplished less than they would usually have done at school or in other activities, and a reduced level of care is noticeable when performing schoolwork or other activities.3

AR is also associated with an increased risk of comorbidities. A recent study showed that allergic conjunctivitis (71.7%) is the most common comorbidity in paediatric patients with severe AR, followed by adenotonsillar hypertrophy (54.1%), sinusitis (49.2%), asthma (46.7%), otitis media (40.8%), atopic dermatitis (20%), chronic tonsillitis (9%), and obstructive sleep apnoea syndrome (4.5%). 3,8

Four pillars of effective management

Bosnic-Anticevich et al, the outcomes demonstrated in their study, were significantly worse in paediatric patients living with inadequate symptom control. Effective AR treatment comprises four important pillars:4,5

In terms of pillar 4, intranasal CS (INCS) are recommended as first-line treatment for paediatric patients living with AR, effectively managing both intermittent and persistent symptoms such as nasal congestion, runny nose, and sneezing. INCS are more effective than first-generation antihistamines (AH) and leukotriene receptor antagonists, particularly in moderate-to-severe AR cases. INCS options such as fluticasone propionate and fluticasone furoate have the lowest systemic bioavailability. 5

efficacy and safety of monotherapy versus combination therapy for AR, aimed at providing evidence-based guidance for pharmacotherapy.9

Their meta-analysis revealed that the combination therapy group exhibited a percentage improvement of 95.2% compared to the monotherapy group, suggesting a greater efficacy in reducing total nasal symptom scores (TNSS) in patients living with AR.9

For children >6-years with difficult-tocontrol symptoms, a combination of AH and INCS is recommended

For children >6-years with difficult-tocontrol symptoms, a combination of AH and INCS is recommended. First-generation AH are not recommended due to their side effects. Second-generation AH can be used as add-on therapy to INCS, especially when itching, sneezing, and runny nose predominate. 5

Nasal decongestants should be used cautiously due to the risk of rhinitis medicamentosa. The use of oral CS is discouraged, and over-the-counter formulations should be avoided. 5

How safe and effective are combination therapy?

Li et al conducted a study to assess the

Effective AR treatment comprises four important pillars

Furthermore, individual nasal symptom scores were significantly reduced in the combination therapy group compared to the monotherapy group. Importantly, there were no significant differences in the incidence of adverse events, such as headache, dysgeusia, and epistaxis, between the two groups.9

The authors concluded that combination therapy significantly improves nasal symptoms in patients living with AR compared to monotherapy, with similar incidence of adverse events between the two groups. The team therefore recommends combination therapy as a preferable option for treating AR.9

Various studies have examined the safety and effectiveness of combination azelastine/ fluticasone nasal spray in different scenarios. Ratner et al demonstrated that this combination significantly improved TNSS by 37.9%. Similarly, Hampel et al found that it enhanced TNSS, improving nasal congestion, runny nose, itchy nose, and sneezing, by 28.4%.10,11

In a recent systematic review and metaanalysis by Debbaneh et al, the combination azelastine/fluticasone nasal spray was found to outperform placebo in reducing TNSS by 60%. The authors of this study concluded that the existing evidence strongly supports the efficacy and superiority of combination azelastine/fluticasone in alleviating symptom scores reported by patients with allergic rhinitis (AR). Consequently, they advocate for considering combination nasal spray as a second-line therapy for patients whose AR symptoms are not adequately managed with monotherapy.12

Conclusion

Viatris’ introduction of the FDC azelastine/ fluticasone nasal spray marks a significant milestone in the management of paediatric AR in South Africa. Research findings demonstrate an impressive 95.2% improvement in TNNS scores compared to monotherapy. As AR profoundly impacts paediatric patients’ and their caregivers’ QoL, combination therapy offers hope for substantial relief.

References are available on request.

Finding relief when you can’t hold it in

When we think of incontinence, we typically associate it with loss of bladder control. However, it’s worth noting that urinary (UI) and faecal incontinence (FI) can co-occur. Double incontinence (DI) is common in frail elderly people and leads to a reduction in quality of life (QoL) and an increased burden on the patients’ caregivers.1,2

Both conditions are often linked to pelvic organ prolapse. More recently smooth-muscle motility disorders (eg detrusor overactivity) have also been implicated. Risk factors for DI include vaginal delivery, hysterectomy, chronic straining and bronchitis, while pudendal neuropathy may contribute to the decline in continence.1,3

Pudendal neuropathy, also known as pudendal neuralgia, is a condition characterised by damage or dysfunction of the pudendal nerve, which is responsible for providing sensation to the genitals, perineum, and rectal area. 4

This condition can lead to symptoms such as chronic pelvic pain, discomfort, numbness, or tingling in the genital and anal regions. Pudendal neuropathy can result from various

causes, including trauma during childbirth, prolonged sitting or bicycling, pelvic surgery, or compression of the pudendal nerve.4

Double whammy

In a cross-sectional, community-based study, the incidence of DI was found to be 9.4%. The prevalence of FI among women with UI ranged from 26% to 35% according to various studies. Another study found that 80% of women with FI also experienced stress UI (SUI).3

MacLennan et al compared the risk of UI and FI between women and men, revealing that women have an 11.7 times higher risk of UI and a 1.6 times higher risk of FI compared to men. 5

UI is classified according to the International Continence Society standards. Subtypes include urodynamic stress

incontinence (USI), detrusor overactivity (DO), and mixed incontinence (MI), each requiring urodynamic assessment for diagnosis.3

FI lacks a clear classification system but can be broadly categorised based on clinical presentation: Urge incontinence and passive incontinence. Research suggests external sphincter dysfunction contributes to faecal urge incontinence, while internal sphincter dysfunction leads to passive incontinence. 3

Impact on QoL of patients and caregivers

The impact of incontinence extends beyond the immediate challenges of managing urinary or faecal leakage. It is associated with several complications that significantly affect an individual’s health and overall QoL. 6

DI can lead to the development of pressure ulcers, particularly in areas where moisture and friction are present. Prolonged contact with urine or faeces can irritate the skin, leading to breakdown and the formation of pressure ulcers and incontinence-associated dermatitis (IAD).

IAD is classified as a type of moistureassociated skin damage and affects the superficial skin barrier, leading to discomfort and increased vulnerability to secondary fungal infections. Excessive moisture, along with friction and shear forces, further compromise the skin barrier’s integrity, increasing susceptibility to damage.6,7

Individuals with DI are at an increased risk of falls, partly due to the need to rush to the bathroom or navigate slippery surfaces when accidents occur. It also increases the risk of urinary tract infections (UTIs).

The constant presence of moisture and potential contamination from faecal matter increases the likelihood of bacterial growth in the urinary tract, leading to infections. 6 DI is also associated with a higher risk of frailty, characterised by decreased physical function, mobility, overall resilience and mortality. Several studies have demonstrated an association between DI and increased mortality rates. The reasons for this association are multifaceted and may include the impact of incontinence on overall health, QoL, and the increased risk of complications such as pressure ulcers and infections, which can contribute to adverse health outcomes.6

In terms of emotional well-being, affected women often avoid leaving home, relying on geriatric napkins or diapers, and

experiencing concerns about urine and/or faeces odours, which can also affect their sex life. These challenges are associated with low self-esteem and impaired mental health. 8

Myths and beliefs about DI being a natural consequence of pregnancy and ageing, combined with feelings of shame and embarrassment, often deter affected individuals from seeking help. 8

Caregiver burden

The challenges faced by caregivers of older adults with incontinence are significant and multifaceted and include physical, emotional, and financial aspects.9

Toileting assistance, a fundamental aspect of caregiving for those with incontinence, involves various tasks that are not only timeconsuming but also emotionally taxing.9

The need for assistance several times a day, including nighttime, can disrupt caregivers’ sleep patterns and overall daily routines. Additionally, the emotional strain of dealing with issues such as odour and the reluctance of older adults to accept help can add to the burden.9

Financially, caregivers shoulder the responsibility of purchasing absorbent incontinence products regularly, which can impose a significant financial strain, especially if the caregiver’s resources are limited.9

Understanding the specific aspects of toileting assistance that contribute most to caregiver burden is crucial for developing targeted interventions. Factors such as urinary/faecal leakage from absorbent products, the type of care

Types of incontinence

setting (home versus nursing home), and the severity of incontinence and associated symptoms all play a role in shaping the caregiving experience.9

Stopping the flow

Urinary incontinence

UI is a component of non-neurogenic lower urinary tract symptoms (LUTS), which encompass a spectrum of issues related to bladder function. LUTS can be broadly categorised into storage symptoms, voiding symptoms, and post-micturition symptoms. UI is classified as a storage symptom.10

Management recommendations include various approaches, such as addressing medical comorbidities and conservative measures, as highlighted by the European Association of Urology (EAU) guideline.10

Older patients often present with multiple comorbid conditions, emphasising the importance of evaluating changes in these conditions or treatments for optimal management.10

Lifestyle factors such as obesity, smoking, physical activity, bowel habits, caffeine, and fluid intake are associated with UI, suggesting that modifying these factors may contribute to symptom improvement in overactive bladder (OAB).10

Behavioural and physical therapies play integral roles in comprehensive care, including prompted voiding, timed voiding, bladder training, cognitive behavioural therapy, pelvic floor muscle training, electrical stimulation, and acupuncture.10

Pharmacological management of LUTS involves careful consideration of efficacy,

UROLOGY | Incontinence

adverse effects, cost-effectiveness, and patient-specific characteristics.10

Anticholinergic agents are recognised as the mainstay of treatment, with various formulations exhibiting differing pharmacological profiles. Immediaterelease preparations offer dosage flexibility but are associated with more adverse effects compared to extended-release formulations.10

Clinical evidence supports the efficacy of antimuscarinics in improving OAB symptoms, although adverse effects such as dry mouth, cognitive impairment, urinary tract infections UTIs, and constipation are common.10

A new antimuscarinic became available in South Africa in 2022. Solifenacin succinate is indicated for the management of OAB, symptoms of urinary urgency, frequent urination and UI.11

Nazir et al conducted a systematic literature review and network metaanalysis (NMA) to compare the efficacy and tolerability of oral antimuscarinics with solifenacin 5mg/day for treating OAB. In terms of efficacy outcomes, the NMA, which included 18 trials (n=10 440) demonstrated solifenacin 5mg/day’s superiority over other antimuscarinics in reducing incontinence episodes. Regarding urgency UI, the NMA, based on 29 trials (n=20 215), highlighted solifenacin’s superiority versus other antimuscarinics in reducing UUI episodes.12

As for tolerability outcomes, dry mouth was assessed across 52 trials (n=32 510), revealing an increased risk compared to solifenacin 5 mg/day with nine of the 19 active comparators.12

Constipation, analysed across 46 trials (n=31 564), indicated a significantly higher risk with solifenacin 10mg/day compared to solifenacin 5mg/day. Blurred vision was assessed across 21 trials (n=17 366), noted no significant differences were noted between solifenacin and other antimuscarinics.12

Beta-3 agonists, particularly mirabegron, represent an alternative pharmacological approach for LUTS. Systematic reviews indicate its efficacy in reducing urgency episodes, UI episodes, and micturition frequency, with a favourable safety profile compared to anticholinergics. Concerns regarding cognitive function in elderly patients have been raised with anticholinergic use, while mirabegron shows no significant impact on cognitive function.10

In their study, Drake et al aimed to assess the efficacy, safety, and tolerability of combining solifenacin 5mg with mirabegron 50mg compared to solifenacin 5mg or 10mg alone in patients with OAB who remained incontinent despite four weeks of solifenacin 5mg treatment.13

Patients diagnosed with OAB who continued to experience incontinence despite four weeks of daily solifenacin 5mg were enrolled. They were randomised in a 1:1:1 ratio to receive either the combination therapy of solifenacin 5mg and mirabegron 50mg, solifenacin 5mg alone, or solifenacin 10mg alone for 12 weeks. Patients receiving the combination therapy started with mirabegron 25mg, which was increased to 50mg after week four.13

Incontinence

is associated with several complications that significantly affect an individual’s health and overall QoL

The primary endpoint was the change from baseline to the end of treatment in the mean number of incontinence episodes per 24 hours. Key secondary endpoints included the change in the mean number of micturitions per 24 hours and the number of incontinence episodes recorded in a threeday diary at the end of treatment.13

Results showed that at the end of treatment, combination therapy was superior to solifenacin 5mg alone, demonstrating significant improvements in daily incontinence episodes, daily micturitions, and incontinence. Furthermore, combination therapy was non-inferior to solifenacin 10mg for key secondary endpoints and superior to solifenacin 10mg in improving daily micturitions. All treatments were well tolerated by the patients.13

Hormone therapy, specifically vaginal oestrogen therapy, has shown benefits in managing genitourinary syndrome of menopause symptoms, including urogenital symptoms.10

Other treatment modalities include bladder wall injection of botulinum toxin A, sacral nerve stimulation, vaginal lasers, and cystoplasty/urinary diversion procedures. While these interventions may offer symptom relief, they are associated with various adverse effects and limited longterm efficacy data.10

Faecal incontinence

faecal material over a period of at least three months. This definition specifically excludes the involuntary passage of clear mucus and flatus.14

The joint European clinical practice guideline for the diagnosis and treatment of FI recommends that the initial step after diagnosing patients should be to alleviate symptoms and enhance patient confidence and QoL.14

Recommended treatment include lifestyle adjustments, dietary modifications (such as increasing fibre and water intake while potentially reducing caffeine and food that may cause bloating and gas), basic behavioural strategies (establishing a regular toilet routine and bowel training), medications to bulk stools or control diarrhoea, pelvic floor muscle exercises, the use of absorbent products, and skincare products to address irritation around the anus.14

However, caution is advised in interpreting the results of some interventions, such as the effectiveness of a low FODMAP diet, due to limited evidence. Furthermore, while certain interventions like psyllium supplementation and anti-diarrheal medications show promise in reducing FI episodes, evidence on the efficacy of lifestyle adjustments like weight loss and smoking cessation is lacking.14

For cases where first-line treatments are insufficient, further diagnostic tests may be considered before initiating secondline treatments. Second-line non-surgical interventions, such as posterior tibial nerve stimulation (PTNS), trans-anal irrigation, and anal inserts, are preferred before resorting to more invasive options.14

PTNS, both percutaneous and transcutaneous, show promise in reducing FI episodes, although the long-term effects need further investigation. Sacral neuromodulation appears to be superior to PTNS in reducing FI episodes and severity, albeit with slightly more adverse events.14

In cases where non-surgical interventions fail to yield satisfactory outcomes, surgical procedures like sphincteroplasty or colostomy may be considered. However, the efficacy of some surgical interventions, such as injectable bulking agents, remains inconclusive, with varying results across studies.14

References are available on request. SF

FI is defined by the Rome IV criteria, as the repeated and uncontrolled discharge of World Continence Week 17-23 June

Women’s teen weight battles may lead to later strokes

A comprehensive analysis, which included five decades of health data, show that women who were overweight or living with obesity at ages 14- or 31-years were more likely to experience an ischaemic stroke before age 55.

An ischaemic stroke occurs when a vessel supplying blood to the brain is obstructed. Ischaemic stroke is the most common type of stroke and accounts for ~87% of all strokes. Conducted in Finland, the study found that women who were overweight at age 14 remained at risk for stroke even if they lost weight by age 31. Similarly, women who became overweight by age 31 had an increased stroke risk regardless of their weight at age 14. Interestingly, men did not show the same increased risk for strokes caused by clots, although those living with obesity at age 31 had a higher risk of bleeding strokes.

According to the lead author of the study, Dr Ursula Mikkola, based in the Research Unit of Population Health at the University of Oulu in Finland, their findings suggest that being overweight may have long-term health effects even if the excess weight is temporary.

To analyse the association between weight at different ages and the risk of stroke before age 55, the researchers reviewed long-term data from participants in the Northern Finland Birth Cohort of 1966.

The Northern Finland study group was initiated to help understand factors related to preterm birth and infant deaths. In 1966, more than 12 000 pregnant women were enrolled from two northern provinces in Finland. More than 10 000 offspring, now in their 50s, have been followed ever since, with their health information used in multiple research studies.

For this analysis, researchers used body mass index (BMI) to explore whether those who were overweight or living with obesity at age 14 or age 31 had a different risk of early stroke compared to peers who were not overweight or obese at age 14 or 31.

About one in 20 participants experienced a stroke caused by a clot or a transient ischaemic attack during the average follow-up period of almost 39 years after the age 14 evaluation, and almost 23 years after the age 31 evaluation. The current study’s analysis ended in 2020.

Assessing the impact of periods of excess weight on stroke risk, the researchers found:

_ Women affected by obesity at age 14 were 87% more likely to have an early clot-caused stroke or mini-stroke, while those with obesity at age 31 were 167% more likely to have a stroke compared to those at appropriate weight. Similar associations were not found among men.

_ Women living with obesity at age 31 had ~3.5-fold increased risk of bleeding stroke, and men with obesity at age 31 had >5.3-fold increased risk of bleeding stroke.

_ BMI measurements earlier in childhood or later in adulthood did not appear to affect the results.

It is important to note that weight is not the only health factor that impacts stroke risk. Many other factors affect stroke risk and should be considered in addition to weight. Eating healthy, not smoking, healthy sleep, managing blood pressure, cholesterol and blood glucose levels, avoiding excess alcohol use and being physically active, can lower the risk of stroke even if an individual was overweight when younger.

Researchers do not know why the association of increased risk for strokes caused by a clot was not found in men. Researchers are investigating the potential causes and other risk factors in more detail.

Reference Mikkola U, Rissanen I, Kivela M, et al Overweight in Adolescence and Young Adulthood in Association with Adult Cerebrovascular Disease: The NFBC1966 Study. Stroke, 2024. SF

CARDIOLOGY | Premature ventricular contractions

Is it normal for the heart to skip a beat and flutter?

PPremature ventricular contraction (PVC), a subtype of ventricular arrhythmia (VA), affects around 1%-4% of the population. Healthcare professionals often view PVC as a benign condition, however, emerging evidence suggests it significantly increases patients’ risk of heart failure (HF), ventricular tachycardia (VT) or ventricular fibrillation, which are associated with adverse cardiovascular (CV) outcomes such as sudden cardiac death.

VCs are caused by abnormal impulse formation or re-entry in the ventricular myocardium or Purkinje system. Characteristics of PVCs include the premature appearance of an abnormal QRS complex (>120m/ sec) with a broad, opposite T-wave and no preceding P-wave.1

Left ventricular outflow tract (LVOT) and right ventricular outflow tract (RVOT) are the most common originator sites of PVCs, accounting for >60% of all cases. RVOT accounts for 70%-80% of cases. Other sites include fascicles, papillary muscles, mitral and tricuspid annuli, and the epicardium.1,2,4,5

PVC often incidentally discovered Patients are often asymptomatic, and PVC may be incidentally discovered during a physical exam or on routine screening electrocardiogram (ECG). Acute symptoms include palpitations, chest pain, shortness of breath, lightheadedness, or dizziness. 2

Progressive symptoms resulting from the cumulative impact that frequent PVCs can have on myocardial contractility, include dyspnoea on exertion, orthopnoea, and oedema and should be an indication for further investigation. Patients living with pre-existing heart disease who

experience frequent PVCs may present with symptoms such as dyspnoea, angina, presyncope, syncope, and even haemodynamic compromise. 2

What tests should be done to confirm a diagnosis?

The initial workup for patients living with suspected PVCs includes a thorough history, physical exam, resting ECG, and at least 24-hours of ambulatory ECG monitoring. If symptoms persist and the initial monitoring is inconclusive, extended monitoring with a 48-hour monitor, event recorder, or implantable loop recorder is recommended. 2

Symptomatic patients should undergo a transthoracic echocardiogram to check for structural abnormalities, focusing on ejection fraction, LV chamber size, valvular issues, and regional wall motion. Additional tests like stress testing, nuclear myocardial perfusion imaging, coronary angiography, and cardiac magnetic resonance imaging (MRI) may be necessary in some cases. 2

Cardiac MRI is useful for diagnosing arrhythmogenic right ventricular cardiomyopathy, infiltrative diseases, or confirming left ventricular non-compaction cardiomyopathy. Evaluating electrolyte

imbalances, specifically potassium and magnesium levels, is also reasonable. Further lab tests, including urine drug screens, thyroid-stimulating hormone levels, cardiac biomarkers, and serum digoxin levels, should be considered when indicated. 2

How are PVCs categorised?

PVCs can be categorised by their pattern relative to normal beats: Bigeminy (a PVC follows each normal QRS complex), trigeminy (a PVC follows every two normal QRS complexes), and multiple successive PVCs. Two consecutive PVCs are called a couplet, three are a triplet, and more than three successive PVCs are termed VT. 2 Couplets are further defined by the interval between the PVC and the subsequent normal beat: Fixed coupling if the interval is stable, and variable coupling if it changes. PVCs are considered frequent if they occur >30 times per hour or constitute more than 20% of total heartbeats. 2

What causes PVC?

Studies show that various lifestyle factors can increase the risk of PVCs. These include stress, caffeine, illicit drug use (eg cocaine),

CARDIOLOGY | Premature ventricular contractions

excessive alcohol intake, cigarette smoking, sleep disturbances, and physical exercise –even in healthy, asymptomatic individuals.1,2

Caffeine and illicit drugs stimulate the heart, while excessive alcohol and nicotine use disrupt electrical pathways, both leading to PVCs. Obesity, insomnia, and stress levels are also linked to higher PVC rates due to autonomic system imbalances.1

PVC can also be caused by electrolyte abnormalities (most commonly hypokalaemia and hypomagnesaemia), volume overload, and hypoxia. Furthermore, the American Heart Association cautions that many commonly used pharmaceutical agents can cause or worsen arrhythmias. Some anti-arrhythmic drugs (AADs), antimicrobials, psychotropic medications, methadone, and a growing list of drugs from other therapeutic classes such as neurological drugs, anti-cancer agents, and others can prolong the QT interval. 2,6

How do you treat symptomatic PVC?

According to Marcus, if PVC burden is low, no underlying structural heart disease is found, reassurance alone may suffice. It should be noted that patients with HF and PVCs tend to have a higher PVC burden, which is a significant risk factor for cardiomyopathy including sudden cardiac death.7

Although there is currently not a definitive threshold for PVC burden, studies do however, suggest that PVC-induced cardiomyopathy is more likely at burdens of 16% to 24%, with most cases occurring at burdens exceeding 10%.7

Catheter ablation is recommended as first-line treatment due to its high success rate and low complication risk. Successful ablation typically involves a combination of activation and pace-mapping guided by fluoroscopy, electro-anatomical mapping, and intracardiac echocardiography. 8

However, like any invasive procedure, the potential benefits of catheter ablation must be carefully weighed against the risk of major complications, which may occur in up to 3% of patients. These complications include vascular issues such as femoral pseudoaneurysm, arteriovenous fistula, or groin hematoma, as well as cardiac perforation leading to tamponade, intraprocedural stroke, or even death. 8

When considering catheter ablation, factors such as pharmacological alternatives, patient comorbidities, the anatomical location of the PVC, and the operator’s experience should all be considered. 8

In cases where symptoms are present, beta-blockers are typically the initial

pharmacological treatment. For patients with a slow baseline heart rate or increased PVC burden due to bradycardia, beta-blockers (BBs) with intrinsic sympathomimetic activity may be particularly beneficial. 8

Alternatively, in patients intolerant to BBs without HF, non-dihydropyridine calcium channel blockers (CCBs) may be considered due to their relatively low adverse effect profile. 8

Second-line treatment includes the use of antiarrhythmic drugs (AADs) such as flecainide or propafenone. Class I and III AADs have shown higher rates of PVC reduction compared to BBs or CCBs. However, Class I AADs were traditionally contraindicated in patients with LV dysfunction or significant structural heart disease.

8

Nevertheless, in a small cohort of patients with suspected PVC-induced cardiomyopathy who had previously undergone unsuccessful ablation procedures, treatment with class IC AADs effectively suppressed PVCs with no adverse events during follow-up. In this cohort, the mean PVC burden decreased significantly, and LV ejection fraction improved. 8

catheter ablation is recommended. 3,6,10

Pharmacological management of idiopathic PVCs aims to reduce cyclic adenosine monophosphate (cAMP) levels, which are elevated in these conditions.9

The latest European Society of Cardiology (ESC) guidelines recommend the following for idiopathic PVC: Betablockers, non-dihydropyridine CCBs or sodium channel blockers when catheter ablation is not available, not desired, or is particularly risky in symptomatic patients with idiopathic PVCs from the RVOT or the left fascicles. Catheter ablation or flecainide should be considered in symptomatic patients with idiopathic PVCs from an origin other than the RVOT or the left fascicles. 3,7,10

When these medications are ineffective or poorly tolerated, other AADs like flecainide, propafenone, sotalol, and amiodarone may be considered.

Flecainide is noted for its high efficacy and tolerability in treating PVCs, though it is contraindicated in patients with structural heart disease due to the risk of re-entrant VAs.9,11,12

Conclusion

Stress, caffeine, illicit drugs, too much alcohol, smoking, sleep disturbances, and exercise can increase the risk of PVCs

PVCs are more prevalent than commonly perceived, affecting between 1%-4% of the population. Despite historically being viewed as benign, emerging evidence suggests PVCs significantly elevate the risk of adverse CV outcomes.

Treating patients with no underlying structural heart disease

Idiopathic PVCs occur in the absence of structural heart disease or inherited ion channelopathies. These PVCs have a focal mechanism related to delayed afterdepolarisations and triggered activity. Stress or exertion often triggers these adrenergically mediated arrhythmias.9

PVCs originating in the RVOT usually appear in patients without structural heart disease. They may present in the form of isolated or incessant PVC, or as tachycardia (up to 80% of idiopathic VT). PVCs originating in the left fascicles are rare. In patients with a cardiomyopathy suspected to be caused by frequent and predominately monomorphic PVCs,

Effective diagnosis and management of PVCs require a comprehensive approach. Pharmacological management typically starts with beta-blockers or CCBs, with AADs reserved for cases refractory to initial therapy.

Catheter ablation has emerged as a firstline treatment option for patients with PVCs originating from specific sites. However, the decision to pursue catheter ablation must be carefully considered, weighing the potential benefits against the risks of major complications.

Ultimately, a tailored approach that considers individual patient factors, symptomatology, and risk profile is essential for optimising outcomes in individuals living with PVCs.

References are available on request. SF

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

CARDIOLOGY | Hypertension

This article was independently sourced by Specialist Forum.

Lifestyle changes key to managing hypertension

The International Society of Hypertension (ISH) recently issued a position paper emphasising the essential role of lifestyle changes in managing hypertension. The ISH recommends lifestyle modifications as first-line treatment to prevent hypertension, which affects over 1.5 billion people globally and is a major driver of cardiovascular disease (CVD). Additionally, the ISH advocates for antihypertensive medications for those diagnosed with hypertension.

Key recommendations include weight loss, increased physical activity, adherence to specific diets, reduction of sodium and sugar intake, moderation of alcohol and caffeine consumption, intermittent fasting, stress reduction, sufficient sleep, and smoking cessation.

Weight loss is one of the cornerstones of hypertension management, with studies demonstrating that even modest reductions in body weight (ranging from 3% to 10% of baseline) can lead to significant improvements in BP levels. This weight reduction often translates to decreased reliance on antihypertensive medications and reductions in both systolic BP (SBP) and diastolic BP (DBP) by ~3mmHg. Furthermore, strategies aimed at reducing abdominal obesity, such as achieving a waist-to-height ratio <0.5 across all populations are recommended.

Regular physical activity is another indispensable component in

Controlling Hypertension in Southern Africa: The New Frontier

The Southern African Hypertension Society Biennial Congress will be held from 16 - 18 August 2024, and we invite all health care practitioners, case managers, medical aid advisors, nurses, pharmacists, primary care providers, researchers, and students from both private and public sectors. The CPD-accredited event features a scientific program with updates on guidelines, clinical lectures, debates, practical advice, ethical discussions, and the latest research. The theme for this year is "Controlling Hypertension in Southern Africa: The New Frontier," focusing on cardiac and kidney disease, stroke, obesity, and genetics. The congress offers multidisciplinary learning, interaction, and networking opportunities with international experts such as Prof Gianfranco Parati, Prof Dike Ojji, Prof Albertino Damasceno, Prof Alta Schutte, and local opinion leaders in hypertension

the battle against hypertension. The benefits of exercise (aerobic and strength training) extend beyond mere weight loss, with each increase in cardiorespiratory fitness correlating with an 8% reduction in hypertension risk.

Dietary modifications play a pivotal role in hypertension management, with the Dietary Approaches to Stop Hypertension (DASH) and Mediterranean diets being widely acknowledged for their effectiveness. These diets advocate for reduced sodium and saturated fat intake while promoting the consumption of high-fibre foods such as whole grains, fruits, and vegetables. Additionally, increasing potassium consumption through dietary sources like fruits, vegetables, nuts, and legumes complements efforts to lower BP.

Limiting the intake of added sugars and alcoho l is paramount, as excessive consumption contributes to metabolic disturbances, adiposity, and insulin resistance, thereby exacerbating hypertension and CVD risk. Similarly, moderation in caffeine consumption (three cups), particularly from sources like coffee and tea, is advised, with evidence suggesting a nonlinear association between intake and cardiovascular outcomes.

Intermittent fasting has garnered attention for its potential benefits in weight loss and blood pressure reduction, though further research is warranted to elucidate its long-term effects.

Stress management techniques, including mindfulness, yoga, and cognitive-behavioral therapy, offer holistic approaches to reduce sympathetic hyperactivity and enhance BP control.

Adequate sleep duration and quality are crucia l for maintaining healthy BP levels, as sleep disturbances disrupt sympathetic nervous system activity and impair BP regulation. Addressing sleep disorders such as obstructive sleep apnoea is essential, as it is considered a significant contributor to secondary hypertension.

Smoking cessation is imperative, given its detrimental effects on CV health. Smokers exhibit acute increases in BP and are at increased risk of CVD. The avoidance of e-cigarette use is also advised due to its potential adverse effects on blood pressure.

To Register Scan with Smart Phone Camera or visit

www.hypertension.org.za

Vitamins, minerals and micronutrients should be part of a healthy, nutrient-rich and balanced diet. Limited evidence suggests a connection between vitamin intake and hypertension, with some studies indicating that multivitamin supplementation may decrease high-BP-related mortality, though not consistently across all populations. Hydro-soluble vitamins and vitamin C supplementation have shown potential in reducing both SBP and DBP. Micronutrient status, including vitamin D, magnesium, potassium, and chlorogenic acids from foods like apples and green tea, may influence BP regulation. Functional foods containing onion, garlic, and catechins from green tea could aid in BP management. However, further research is needed to fully understand their impact on hypertension.

Reference available on request. SF

The advent of non-vitamin K antagonist oral anticoagulants (NOACs) such as apixaban represented a pivotal advancement in stroke management among patients living with atrial fibrillation (AFib).

Traditionally, it was believed that reducing the frequency of dosing (eg once-daily dosing) could enhance adherence. Comparisons between once-daily and twice-daily dosing regimens reveal that despite a higher percentage of prescribed doses being taken with once-daily dosing, twice-daily dosing ensures a greater degree of continuity in drug action.

Furthermore, stress Vrijens and Hedibuchel, while once-daily dosing may appear to simplify dosing regimens and improve patient adherence, it requires nearperfect adherence to achieve intended pharmacodynamic and clinical outcomes. In contrast, twice-daily dosing, depending on the agent’s pharmacokinetics, is more forgiving of variations in dose timing or

occasional missed doses.

According to Ido et al, opting for twicedaily dosing over once-daily dosing could theoretically reduce the peak level of drug concentration in both the gut lumen and blood plasma. This adjustment may lead to a narrower range of drug concentration within the twice-daily regimen compared to the once-daily regimen, potentially contributing to an improved safety profile. Clemens et al compared the risk-benefit balance between twice- and once-daily dosing regimens of NOACs. The authors concluded that twice-daily dosing regimen appears to offer a more balanced riskbenefit profile concerning stroke prevention and intracranial haemorrhage.

A recent study by Hwang et al assessed

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Is twice-daily dosing the key to unlocking optimal anticoagulation benefits?

the impact of once- or twice-daily dosing on adherence and clinical outcomes in patients living with AFib. The study found that 95% of patients achieved high adherence to NOAC therapy, with no significant differences observed based on dosing regimen. Across all dosing regimens, the mean proportion of days covered for NOACs was ~96%.

Notably, adherence was highest among apixaban users, followed by rivaroxaban users, and lowest among dabigatran users, irrespective of dosing frequency. Adverse outcomes were more prevalent among patients with low adherence to NOAC therapy, regardless of the dosing regimen.

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

20

INFECTIOUS DISEASES | Hepatitis C

Changing the trajectory of Hepatitis C infections in SA

Viral hepatitis presents a substantial public health concern, with ~304 million individuals worldwide living with chronic hepatitis B (hep B) and C (hep C) infections in 2022. An estimated 50 million individuals were infected with the hep C virus (HCV). Regrettably, viral hepatitis accounted for around 1.3 million deaths, equating to an alarming average of 3651 deaths per day. Hep C contributed to 17% of these fatalities.1

An estimated eight million individuals in the African region are living with HCV. Furthermore, ~172 000 new infections are reported in the African region annually. Importance of screening, testing and diagnosing HCV Between 15%-25 % of infected individuals naturally eliminate the virus within six months.1

However, the remaining 75%-85% will progress to chronic hep C. Among those with chronic infection, the risk of cirrhosis ranges from 15%-30% within 20 years, with an annual risk of hepatocellular carcinoma ranging from 1%-4%. 2

The authors of the South African National Department of Health’s Guidelines for the Management of Viral Hepatitis, stress that without proper diagnosis and treatment, ~30 % of individuals chronically infected with viral hepatitis will die as a result of severe liver conditions such as cirrhosis, liver failure, and hepatocellular carcinoma. 2

According to the World Health Organization (WHO) Global Hepatitis Report 2024, two major challenges in the effective management of hep C in the African region are the lack of diagnostics and access to curative treatment. Currently, only South Africa and Rwanda provide hep C diagnosis and treatment free of charge in the public sector, either fully or partly for specific subpopulations.1

In the African region, only ~13% of

individuals living with chronic HCV were diagnosed, and only ~3 % had access to treatment in 2022. Diagnostic coverage (24%) and access to treatment (19 %) were slightly better in South Africa compared to the rest of Africa.1

Subpopulations at risk of HCV infection

Subpopulations at high risk of HCV infection include individuals who inject drugs, men who have sex with men (particularly those living with HIV), patients living with HIV, and the incarcerated population. 3,4

Findings from a South African study suggest that ~50 % of individuals who inject drugs, and between 3%-6% of men who have sex with men, especially if HIV positive, are re living with chronic Hep C virus infection. 2

Among South Africans who inject drugs, there is notable regional disparity in viraemic prevalence, with the highest rates observed in Pretoria (~84%) and between 30%-40 % in Durban and Cape Town. 2

The prevalence of documented HIV/HCV co-infection in South Africa varies from 1% to 13.4%. This co-infection significantly alters the natural progression of HCV and is considered a priority for treatment with direct-acting antivirals (DAAs). 2

This is due to several factors, including accelerated fibrosis leading to cirrhosis, increased risk of hepatocellular carcinoma,

increased HCV transmission risk (especially mother-to-child transmission), elevated susceptibility to liver injuries induced by antiretroviral therapy and tuberculosis medications, and reduced effectiveness of interferon-based therapy. 2

In sub-Saharan Africa, hep C transmission risk also arises in healthcare settings due to unsafe medical practices. In South Africa, unsafe medical practices account for 10% of cases. 3,4

Additional risk groups include healthcare professionals (due to occupational hazards like needle stick injuries), and individuals undergoing chronic haemodialysis (~10%) or surgical procedures including dental or orthodontic procedures without adequate sterilisation. Furthermore, individuals involved in high-risk or traumatic sexual practices, intranasal cocaine users, or those who have tattoos or body piercings done, or opt for acupuncture procedures, are at increased risk. Traditional or cultural practices such as circumcision and scarification rituals also pose potential risks. 2

Despite a historically secure blood and blood products supply system, individuals living with haemophilia, and those who received blood or blood products before 1992 are at risk of infection. During acute hep C infection, individuals may experience symptoms such as malaise, nausea, and right upper quadrant pain, followed by dark

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

INFECTIOUS DISEASES | Hepatitis C

urine and jaundice. These manifestations are clinically similar to those of other acute viral hepatitis cases. 4,5

Chronically infected individuals typically remain asymptomatic. Symptoms, when present, are non-specific and may include fatigue, intermittent right upper quadrant pain, joint pain, and a general feeling of being unwell, leading to a reduced overall quality of life. However, attributing these symptoms solely to hep C is challenging, as there may also be a psychological component due to the awareness of having an underlying chronic disease. 5

Prevalent hep C genotypes in SA and symptoms

There are six clinically significant hep C genotypes and over 80 subtypes. The prevalence of genotypes varies depending on the geographic region and the route of acquisition. In South Africa, multiple genotypes, including 1 to 5, are observed, with genotypes 1 and 5 being the most common, and genotype 4 being increasingly detected. 2

Notably, genotype 5a, initially discovered in South Africa, is unique to the region. This viral genotype significantly influences the response to interferon/ribavirin combination therapy, but not with the newer DAAs. 2

The DAA revolution

DAAs have changed the trajectory of hep C management. DAA therapy boasts a high sustained viral response rate (SVR) at 12 weeks post-treatment completion and is linked with a decreased risk of mortality and hepatocellular carcinoma. 6

According to the National Department of Health guidelines for the management of viral hepatitis, all patients with hep C must be offered therapy unless concomitant co-morbidities will result in short-term mortality. 2

The WHO recommends pan-genotypic DAA regimens for all adults, adolescents and children (≥3-years) living with chronic hep C, regardless of the stage of the disease.1

In South Africa, registered pan-genotypic DAA regimens are recommend for children >12-years. Pan-genotypic regimens include sofosbuvir/velpatasvir (SOF/VEL). Nonpangenotypic DAA regimens may be considered in settings where genotype 3 is minimal.1,2

How effective is sofosbuvir-velpatasvir?

The fixed-dose combination (FDC) of SOF/VEL became available in South Africa in 2023. It is approved for treating chronic hep C infection, regardless of

genotype, in both treatment-naïve and treatment-experienced patients aged ≥12-years, weighing at least 30kg, and without cirrhosis or with compensated cirrhosis. This regimen can also be used in combination with ribavirin for patients with decompensated cirrhosis.7

SOF/VEL is the first pan-genotypic, panfibrotic, protease inhibitor-free, all-oral single-tablet regimen and can be used as a fixed 12-week treatment duration in all adult patients with chronic hep C. 8

FDC SOF/VEL is a once-daily singletablet regimen that combines two pangenotypic antiviral agents with high potency, a high genetic barrier, and with favourable safety and tolerability profiles observed in a wide range of patients, including those with decompensated cirrhosis. SOF is a nucleotide analogue inhibitor targeting the HCV NS5B polymerase. VEL is a last generation, pangenotypic HCV NS5A inhibitor.9

In a comprehensive real-world analysis conducted by Mangia et al, the effectiveness of SOF/VEL without ribavirin in achieving SVR in individuals (n=5552) living with hep C was assessed across 12 clinical cohorts worldwide. 8

Some 13.3% of participants were treatment-experienced, 20.7% had liver cirrhosis, 30.2% were infected with genotype 1, 29.5% with genotype 2, 32.9% with genotype 3, and 4.7 % with genotype 4. Furthermore, 3.7% were living with HIV co-infection, 13.4 % were current/former intravenous drug users. 8

Overall, 98.9% of patients achieved SVRs with high rates observed across all genotypes, including genotype 3 (98.3%) and among those with compensated cirrhosis (97.9%). Compensated cirrhosis was identified as a significant risk factor for not achieving SVR. Non-virological reasons accounted for 6% of cases not achieving SVR, primarily due to loss to follow-up or early treatment discontinuation. 8

In the Sofosbuvir and Velpatasvir for HCV Genotype 1, 2, 4, 5, and 6 Infection (ASTRAL 1) study, Feld et al (2015) demonstrated that once-daily SOF/VEL for 12 weeks achieved high rates of SVR (99 %) among patients infected with hep C genotypes 1, 2, 4, 5, or 6, including those with compensated cirrhosis.10

In the Sofosbuvir and Velpatasvir for HCV Genotype 2 and 3 Infection (ASTRAL 2 and 3) study, Foster et al (2015) assessed the efficacy of SOF/VEL compared to SOF-ribavirin. Participants included some living with compensated cirrhosis. Among patients with genotype 2, the SOF/VEL group achieved a significantly

higher SVR rate of 99% compared to 94% in the SOF-ribavirin group. Similarly, among patients with genotype 3, the SVR rate was notably higher in the SOF/VEL group at 95%, compared to 80% in the SOF-ribavirin group.11

Furthermore, Curry et al (2015) highlighted the increasing prevalence of decompensated cirrhosis among HCVinfected individuals. In the Sofosbuvir and Velpatasvir for HCV in Patients with Decompensated Cirrhosis (ASTRAL 4), SVR rates of 83% were reported in individuals living with decompensated cirrhosis who received 12 weeks of SOF/VEL, 94% among those who received 12 weeks SOF/VEL plus ribavirin, and 86% among those who received 24 weeks of SOF/VEL.12

Wyles et al (2017) assessed the efficacy of SOF/VEL in patients coinfected with HCV and HIV-1 in the Sofosbuvir and Velpatasvir for the Treatment of Hepatitis C Virus in Patients Coinfected with Human Immunodeficiency Virus Type 1 (ASTRAL 5) study, demonstrating favourable SVR rates and safety profiles.13

In addition, the AIDS Clinical Trials Group A5360 Minimal Monitoring trial explored simplified monitoring strategies for hep C treatment, emphasising the use of SOF/ VEL. The trial revealed high SVR rates (95%) and safety outcomes (4% of the study population experienced adverse effects) with minimal monitoring, suggesting the potential for this approach to enhance treatment accessibility and contribute to global hep C elimination efforts.14

Conclusion

Hep C infection remains a significant global healthcare challenge, with millions of individuals affected. The introduction of pan-genotypic effective treatments like SOF/VEL represents a crucial advancement in hep C management, offering high cure rates across diverse patient populations, including those with compensated cirrhosis. Real-world analyses have demonstrated the effectiveness of SOF/VEL in achieving SVR rates >98 % across various genotypes and patient cohorts. Importantly, SOF/ VEL’s once-daily single-tablet regimen and predictable safety profile make it an option for simplifying treatment and improving adherence. However, challenges persist, including limited diagnostic coverage and treatment access, especially in resourceconstrained settings. Efforts to expand screening, testing, and treatment initiatives are crucial for maximising the impact of SOF/VEL and moving closer to the goal of hep C elimination by 2030.

References are available on request. SF

This article was independently sourced by Specialist Forum.

Revolutionising HIV treatment in South Africa: The advantages of switching to TLD

According to a Human Sciences Research Council report, HIV prevalence in South Africa decreased from 14% in 2017 to 12.7% in 2022. However, prevalence varies across regions, genders, ethnicities, and age groups, ranging from 8% in the Western Cape to 22% in KwaZulu-Natal. Women and individuals of African descent have higher prevalence rates compared to men and other ethnic groups.

Antiretroviral treatment (ART), introduced in the public sector in 2004, has dramatically reduced HIV-related deaths and improved health outcomes. By 2010, ART had contributed to a 51% global reduction in HIV-related deaths. In South Africa, ART availability has led to a yearly 27% reduction

in mortality among adults aged 25 to 49 years and a 35% decrease in poor health reporting.

The treatment landscape evolved significantly with the development of combination therapies. Initially, monotherapy with azidothymidine (AZT) faced challenges due to rapid drug resistance. The introduction of protease inhibitors (PIs), nucleoside reverse transcriptase inhibitors (NRTIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs) marked a shift in HIV treatment.

Subsequent advancements included integrase strand transfer inhibitors (InSTIs) like dolutegravir (DTG), which, in combination with other drugs, became a preferred treatment due to its efficacy, ease of administration, and reduced risk of side effects.

South Africa, with the world’s largest population of people living with HIV (7.6 million), has made notable progress in reducing HIV infection rates and related mortality since the first reported case in 1982.

Current guidelines recommend initiating treatment with a combination of two NRTIs and an InSTI, PI, or NNRTI, with DTG being the favoured option. DTG-based regimens, such as tenofovir disoproxil fumarate/ lamivudine/dolutegravir, offer superior potency, durability, and fewer side effects compared to older regimens.

These combinations have simplified treatment protocols, improved patient adherence, and reduced costs. Updated guidelines by South African health authorities advocate for transitioning eligible patients to DTG-based regimens to enhance treatment outcomes.

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

– a TLD regimen by Cipla.1

Patients currently on TDF +FTC/3TC and EFV or NVP should be switched to TLD regardless of whether their VL is suppressed or not suppressed. 2

One-size treatment approach to HIV does not fit all

RPV, a second-generation nonnucleoside reverse transcriptase inhibitor, disrupts viral replication by binding to the reverse transcriptase enzyme. FTC and TAF, both nucleoside reverse transcriptase inhibitors, inhibit viral DNA chain elongation, further preventing replication.

When prescribing ART, individual patient factors such as age, comorbidities, social status, lifestyle, and genetic makeup are crucial in tailoring treatment. Monitoring the efficacy and side effects of ART regimens is essential, with adjustments made for drug toxicity or resistance.

The World Health Organization and South African guidelines recommend a first-line regimen of tenofovir disoproxil fumarate (TDF), lamivudine (3TC), and dolutegravir (DTG), with alternative options including efavirenz (EFV) and RPV.

While DTG is well-tolerated, EFV can cause neuropsychiatric events and, rarely, severe conditions like Stevens-Johnson syndrome. TDF can lead to renal and bone toxicities, while TAF, designed to minimise these issues, may result in greater weight gain and adverse lipid profiles.

Switching to the single-tablet RPV/FTC/ TAF formulation has proven effective and

South Africa’s antiretroviral therapy (ART) regimen has been significantly enhanced with the introduction of a new single-tablet formulation combining rilpivirine (RPV), emtricitabine (FTC), and tenofovir alafenamide (TAF). This combination provides a convenient and effective treatment option for HIV, marking a pivotal development in managing the disease. safe. Studies have demonstrated noninferiority in maintaining viral suppression compared to previous regimens. The new formulation also showed fewer adverse effects, particularly in renal and bone health.

RPV/FTC/TAF represents a significant advancement in HIV treatment, offering a more convenient, effective, and safer option for patients, thereby enhancing adherence and overall management of the disease.

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

ONLINE CPD: INFECTIOUS DISEASES |

Rethinking the necessity of three-drug ART

Recently, the focus has shifted towards dual ARV therapy, potentially reducing overall drug exposure, mitigating specific toxicities, and lowering costs. Dual regimens, particularly those involving dolutegravir (DTG) with either lamivudine (3TC) or rilpivirine (RPV), have gained traction. In 2018, a single-tablet regimen combining DTG and RPV was approved, followed by DTG/3TC in 2020. DTG/3TC became the first dual regimen approved as first-line therapy for treatment-naïve individuals. In South Africa, both DTG/3TC and DTG/RPV became available in 2022.

The 2023 Southern African HIV Clinicians Society guidelines recommend switching

most patients to DTG-based regimens, with dual therapy being an option under specific conditions, such as excluding hepatitis B before considering DTG/3TC. Additionally, DTG/3TC should not be used for rapid ART initiation without available lab results.

Clinical trials, including the ASPIRE, TANGO, and GEMINI studies, have shown that DTG/3TC is non-inferior to triple therapy in maintaining virologic suppression, with similar adherence rates, safety profiles, and minimal resistance development. The SALSA trial further confirmed the effectiveness of DTG/3TC in maintaining suppression, highlighting improvements in renal and bone health markers.

For DTG/RPV, the SWORD studies

In the mid-1990s, the standard HIV treatment paradigm shifted to triple antiretroviral (ARV) regimens, which effectively suppressed viral replication and minimised resistance development. Despite the efficacy of this approach, long-term adverse effects necessitated considering the minimum drug number needed for effective treatment. demonstrated its non-inferiority in maintaining suppression compared to triple regimens, with manageable adverse effects.

Real-world studies also support the efficacy and safety of DTG/RPV, showing high rates of viral suppression and favourable safety profiles even in individuals with extensive treatment histories.

Overall, switching to dual regimens like DTG/3TC and DTG/RPV is a viable option for maintaining virologic suppression, offering simplified treatment while mitigating long-term adverse effects associated with triple therapy.

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

An option for patients who are virologically suppressed (VL < 50 copies / mL) while receiving a regimen of NNRTI + two NRTIs, and who have never experienced virological failure, is a switch to the two-drug combination of DTG + RPV.2

DISEASES

This article was independently sourced by Specialist Forum.

Managing dermatological conditions in individuals living with HIV

Dermatological conditions represent a significant burden among individuals living with HIV (ILWH), further impacting their quality of life and overall health outcomes. It is crucial that dermatologists and healthcare providers understand and effectively manage these conditions.

Dermatological conditions are common in ILWH, affecting up to 90% of individuals during the course of their disease. While some conditions may occur with similar frequency as in the general population, others, such as psoriasis, seborrheic dermatitis (SD), and papular pruritic eruption (PPE), exhibit distinct clinical features in the context of HIV. Furthermore, severe cutaneous adverse drug reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), are more prevalent in ILWH, posing significant challenges in management.

Dermatological conditions may present differently in ILWH Psoriasis, a chronic inflammatory skin condition, may present differently in ILWH compared to the general population. While plaque psoriasis remains the most common manifestation, atypical morphologies such as rupoid, sebopsoriasis, and annular forms are more prevalent in ILWH.

Diagnosis can be challenging due to clinical mimickers and coexisting conditions like tinea and secondary syphilis. Treatment options include topical medications, oral retinoids, phototherapy, and systemic therapies like cyclosporine and methotrexate, with careful consideration of potential drug interactions with antiretroviral therapy (ART).

SD, characterised by erythematous and greasy scales, is significantly more common in ILWH, although its prevalence has decreased with ART. HIV-associated SD may present with more severe manifestations, requiring systemic antifungal therapy in refractory cases. ART has shown efficacy in managing SD, underscoring the importance of viral suppression in controlling dermatological conditions.

PPE, marked by pruritic papules on the trunk and extremities, mostly affects individuals with higher levels of immunosuppression. Differential diagnosis includes conditions like acne and eosinophilic folliculitis, necessitating biopsy for confirmation. Treatment involves ART as first-line therapy, supplemented with antihistamines and topical steroids for symptomatic relief.

EF, characterised by pruritic follicular papules, is associated with low CD4+ counts. Diagnosis can be clinical but may require biopsy for confirmation. ART remains the cornerstone of treatment, with phototherapy and oral agents can be considered for refractory cases. SJS/TEN, although rare, are more with certain medications like nevirapine. Management involves discontinuing the offending drug and providing supportive care, with systemic steroids used cautiously. Additionally, drug reactions with eosinophilia and systemic symptoms may occur in ILWH, necessitating prompt discontinuation of the culprit medication and consideration of systemic steroids.

Conclusion

Dermatological conditions pose unique challenges in the management of ILWH, requiring tailored approaches that consider both HIV and dermatological aspects.

With advancements in ART and evolving treatment options, effective management of these conditions is achievable, enhancing both patient outcomes and QoL.

Collaboration between dermatologists, HIV specialists, and other healthcare providers is essential in optimising care for ILWH and dermatological conditions.

References are available on request. SF

This article was independently sourced by Specialist Forum.

Stopping the surgical stress cascade

Globally, >310 million major surgeries are performed annually. It is estimated that 1%4% of patients who undergo major surgery will die, up to 15% will experience serious post-operative complications, and 5%-15% will be readmitted within 30 days. With an annual global mortality of ~8 million patients, major surgery ranks among the leading causes of death, comparable to CV disease, stroke, cancer, and injury.1

According to Dobson, a key starting point to prevent and manage complications after major surgery is to recognise that the anaesthetised brain is still physiologically ‘awake’ and responsive to surgical stress.1

Surgical stress is defined as an acute response to breaches in the body’s barrier functions due to sterile injury (such as incision, excision, manipulation, and pain), pathogen invasion (such as gut bacterial translocation or postoperative wound infection), and anaesthesia.1

This stress response starts with increased sympathetic discharge following anaesthesia induction and the first incision. If uncontrolled, it disrupts whole-body homeostasis, increasing inflammation, altering coagulation, modifying immune competency and T cell mobilisation via β2-adrenergic pathways, heightening infection susceptibility, and reducing tissue oxygenation.1

This cascade of secondary injuries can lead to multiple organ dysfunction by disrupting homeostatic circuits connecting the brain, heart, lungs, kidneys, liver, gut, and muscles.1

It should be noted that the trauma of surgery alone is not the only contributor to secondary injury. Intraoperative bleeding, coagulopathy, cardiac issues, metabolic dysregulation, and organ

dysfunction also play critical roles. These factors are closely linked to the patient’s physiological reserve and overall stress response.1

The extent of a patient’s stress response to surgery is influenced by factors such as the type and duration of surgery, age, gender, ethnicity, health status, medication profile, prior surgeries, and other variables. Generally, open surgical procedures trigger a greater stress response compared to less invasive laparoscopic or robotic surgeries.1

Major non-cardiac surgeries, such as median sternotomies, thoracotomies, laparotomies, abdominal hysterectomies, and orthopedic hip or knee replacements, elicit significant stress responses.1

Can the stress response be controlled?

The Systems Hypothesis of Trauma (SHOT) postulates that the central nervous system (CNS) is the primary controller of the stress response and by targeting the hypothalamic-pituitary-adrenal axis and nucleus tractus solitarius in the anesthaetised brain, interventions may improve CV function, endothelial health, tissue perfusion, and energy production. Key pillars of this approach include CNS-CV coupling, endothelial glycocalyx health, and mitochondrial integrity.1

CNS-CV coupling

CV complications are a leading cause of death within 30 days post non-cardiac surgery. Suppressing CNS neurohormonal outflows before surgical stress is essential for protecting cardiovascular function and preventing secondary injury. Ventricular-arterial (VA) coupling, defined as the ratio of left-ventricular elastance to arterial elastance, is a crucial parameter linking CNS to cardiac output and endothelial health. Optimal VA coupling ensures efficient CV performance, while imbalances can lead to adverse clinical outcomes, including reduced blood flow to major organs, hyperinflammation, coagulopathy, and immune dysfunction.

Endothelial glycocalyx health

The endothelial glycocalyx plays a vital role in coupling CNS-CV function to oxygen transport and energy production. Surgical stress and related factors such as hypoperfusion, ischaemia-reperfusion injury, and inflammation can lead to glycocalyx shedding, causing widespread inflammation, coagulopathy, and vascular dysfunction.

Protecting the endothelial glycocalyx through drug therapies may improve postoperative outcomes. Although specific peri-operative treatments are not yet available, promising strategies are being developed using various drugs and liposomal nanocarriers.

Mitochondrial integrity

Surgical-induced ischaemia can cause mitochondrial dysfunction and oxidative stress in peripheral tissues, immune cells, and platelets. This dysfunction is linked to impaired myocardial function, contractile dysfunction, and ventricular arrhythmias.

Protecting mitochondrial function is crucial for maintaining cellular energy production and preventing secondary injury. New therapies targeting mitochondrial integrity could help reduce surgical stress and its complications.

Reference available on request. SF

Closing the critical knowledge gaps in diabetes management

Diabetes, a chronic condition affecting millions worldwide, imposes significant challenges to individuals and healthcare systems alike. Its implications extend far beyond blood sugar control, encompassing a myriad of complications that can severely impact quality of life (QoL) and longevity.

Lower limb amputation, cardiovascular diseases, retinopathy, neuropathies, and nephropathy are among the long-term complications associated with diabetes, often resulting in debilitating consequences and, tragically, premature death.

Statistics paint a grim picture

In 2021 alone, diabetes claimed 6.7 million lives globally. Alarming still is the revelation that in South Africa, >38% of people with diabetes are unaware of their status, increasing, the risk of more severe disease progression and increased risk of complications. According to Statistics South Africa, the demographic hardest hit by diabetes falls within the age range of 21- to 79-years. In 2018, the direct cost incurred for diagnosed, treated, and controlled patients were >2.7 billion. Notably, 50% of this expenditure was allocated to the treatment and management of type 2 diabetes (T2DM).

Management complexities

Management of diabetes is complex. The pathophysiology of T2DM is linked to socioeconomic determinants, lifestyle factors, and genetic predispositions. While genetics plays a role in predicting the risk of developing T2DM, it is the interplay of physical and social determinants that significantly influences its onset and progression. Thus, conventional treatments must be complemented with behavioral changes, dietary modifications, regular physical activity, and vigilant disease management to effectively mitigate its impact.

Gap in patient knowledge

Crucially, individuals living with diabetes must be empowered to monitor their health status diligently, ensuring adherence to medication regimens and lifestyle recommendations. However, studies indicate a concerning gap in knowledge among diabetes populations, particularly concerning follow-up care, dietary choices, and physical activity. This underscores the importance of widespread education on diabetes management and the adoption of healthy lifestyles. Diabetes education is a linchpin in transforming behaviours, fostering disease self-management, and ultimately enhancing health outcomes. Meta-analyses of randomised controlled trials have shown the efficacy of educational interventions in improving diabetes-related knowledge and glycaemic control. Furthermore, understanding one’s illness perception and diabetes knowledge are pivotal in driving self-care practices and informed decision-making regarding exercise, diet, medication use, and health monitoring.

Misconceptions and knowledge gaps

Pervasive misconceptions about diabetes persist, negatively impacting effective diabetes management. Studies reveal alarming beliefs among individuals living with diabetes, such as the notion that only sugar impacts blood glucose levels or that bitter foods can reduce elevated levels. Furthermore, there are concerning knowledge gaps regarding medication effects and self-care practices, further

exacerbating the challenge of disease management.

Ferreira et al conducted a study to assess the diabetes knowledge among individuals with T2DM and identified critical gaps and areas for intervention. The study revealed significant disparities in knowledge levels, particularly concerning the identification of ketoacidosis signs and appropriate dietary choices during hypoglycaemia. Such insights are invaluable in tailoring targeted interventions to bolster patient knowledge and prevent potentially life-threatening complications.

Conclusion

Addressing knowledge gaps in diabetes management is crucial to enhance patients’ QoL and curbing the staggering burden of this disease. By prioritising comprehensive education, promoting selfmanagement practices, and fostering informed decision-making, individuals living with diabetes can be empowered to navigate their disease effectively and mitigate its devastating consequences. References are available on request. SF

This article was independently sourced by Specialist Forum.

Uncontrolled BP: What to do

In this webinar entitled: My patient’s blood pressure is not controlled. What should I do? Prof Brian Rayner explored the subject of uncontrolled hypertension and offered valuable insights and practical tips on addressing this issue.

This webinar was sponsored by Viatris in the interest of education, awareness, and support. The content and opinions expressed were entirely the speakers’ own work and not influenced by Viatris in any way. This webinar is accredited for one (1) CPD point. Certificates of attendance are available for attendees from other countries on request.

Diagnosing resistant hypertension

Defining resistant hypertension is pivotal in understanding the scope of the problem. The criterion for identifying resistant hypertension is inadequate blood pressure (BP) control despite being on multiple antihypertensive medications.

It is extremely important to exclude factors such as non-adherence or white coat effect before confirming true resistance, stressed Prof Rayner.

Factors contributing to resistance include age, obesity, salt intake, chronic kidney disease, diabetes, and race, with individuals of African descent being particularly susceptible.

Non-adherence and medicationrelated issues are identified as significant contributors to apparent resistance, underscoring the necessity for thorough diagnostic evaluation.

He highlighted the disparity in hypertension control between high-income countries and regions like sub-Saharan Africa. While there has been notable improvement in control rates in the former,

the latter continues to face challenges with rising prevalence rates.

Furthermore, he stressed that importance of timeous diagnosis and initiation of effective treatment, urging healthcare professionals at all levels to prioritise hypertension management.

Diagnostic approaches include accurate BP measurement using automated devices. Ambulatory BP monitoring is recommended to differentiate true resistance from white coat effect. Lifestyle modifications, including dietary changes and exercise are essential components of hypertension management.

Secondary causes of hypertension are addressed, with a call to consider and investigate conditions such as renal artery stenosis or primary aldosteronism.

Combination therapy as initial treatment

According to Prof Rayner, combination therapy should be used as first-line initial treatment. Specifically, a combination of an angiotensin receptor blocker or angiotensin-converting enzyme inhibitor with a calcium channel blocker (CCB) is often prescribed. Prof Rayner pointed out a deviation in treatment approach for patients of African descent, who may commence therapy with a CCB and a diuretic combination.

In cases of resistant hypertension, the addition of low-dose spironolactone is recommended, with careful monitoring for hyperkalaemia. Other treatment

options include doxazosin, beta-blockers, and loop diuretics, chosen based on patient characteristics and response to previous  herapies.

Prof Rayner stressed the importance of optimising medication dosing and addressing secondary causes of hypertension to achieve optimal blood pressure control.

Conclusion

The multifaceted nature of hypertension management requires a holistic approach that includes lifestyle modifications, adherence promotion, and appropriate medication selection.

To watch a replay of the video, click here or scan the QR code. If you watched the replay video, please send an email to john.woodford@newmedia.co.za to claim your CPD point. Include the name of the webinar in the subject line and your HPCSA number in the text. You can also email John for a certificate of attendance. Please confirm the validity of the certificate of attendance with your regulatory body. SF

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Viatris CV portfolio - Helping you prevent microvascular and macrovascular diseases 1, 2

References:

1. Petrie JR, Guzik TJ, Touyz RM. Diabetes, Hypertension, and Cardiovascular Disease: Clinical Insights and Vascular Mechanisms. Canadian Journal of Cardiology 2018; 34: 575-584. 2. 2018 ESC/ESH Guidelines for the management of arterial hypertension. European Heart Journal 2018; 39: 3021–3104. doi:10.1093/eurheartj/ehy339

S3 MIZART 40 mg, 80 mg (tablets) Reg.Nos: 45/7.1.3/0606, 45/7.1.3/0607. Each tablet contains telmisartan 40 mg and 80 mg respectively. Contains sugar: Mannitol 170,200 mg and 340,400 mg respectively.

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For full prescribing information refer to the professional information approved by the medicines regulatory authority. Viatris Healthcare (Pty) Ltd. Reg No: 1949/035112/07, 4 Brewery Street, Isando, Gauteng, 1609. Tel: 011 451 1300. www.viatris.co.za.

S3 LOMANOR 5 mg, 10 mg (tablets) Reg.Nos: 38/7.1/0271, 38/7.1/0272. Each tablet contains amlodipine besylate equivalent to 5 mg and 10 mg amlodipine base respectively. Sugar free. S3 MYLACAND 8 mg, 16 mg (tablets) Reg.Nos: 45/7.1.3/0301, 45/7.1.3/0302. Each tablet contains candesartan cilexitil 8 mg and 16 mg respectively. Contains lactose (sugar).

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For full prescribing information refer to the professional information approved by the medicines regulatory authority. Viatris South Africa (Pty) Ltd. Reg No: 1991/003162/07, 4 Brewery Street, Isando, Gauteng, 1609. Tel: 011 451 1300. www.viatris.co.za.

AML-2024-00001 Exp 04/2026

The interplay between

allergic rhinitis and asthma

Prof Claudia Gray, a paediatrician with specialised accreditation in allergology and paediatric pharmacology, part-time consultant at the Allergy and Asthma clinic at Red Cross Children’s Hospital, and an Associate Professor in Paediatrics at the University of Cape Town, recently presented a webinar on the interplay between allergic rhinitis (AR) and asthma. The webinar was sponsored by Inova in the interest of education, awareness, and support.

AR, often known as hay fever, extends beyond being a mere seasonal inconvenience. It manifests when the immune system reacts excessively to harmless substances, resulting in symptoms like itching, sneezing, congestion, and eye irritation.

Despite sometimes being trivialised, AR can significantly impact both physical and emotional well-being, causing discomfort and reducing functionality in daily life. Understanding the immune response involved in AR reveals the formation of specific immunoglobulin E antibodies upon initial allergen exposure. Upon subsequent encounters, these antibodies trigger mast cells to release various mediators, leading to symptoms like itching, sneezing, and congestion. Additionally, cytokines released during this process can perpetuate inflammation, worsening symptoms over time.

Traditional classification focused on seasonal versus perennial AR, but newer guidelines prioritise symptom duration and severity. Allergic Rhinitis and its Impact on Asthma guidelines categorise AR into intermittent and persistent forms, with further subdivisions based on impact on quality of life (QoL). AR, especially when moderate to severe, disrupts sleep, hinders work or school performance, and interferes with leisure activities.

It is vital to recognise AR’s substantial impact beyond inconvenience and address it comprehensively to improve patients’ QoL, stressed Prof Gray.

Early testing for environmental allergies in children is feasible and beneficial, helping differentiate between infections and allergies for appropriate treatment.

Myths and misconceptions

Correcting misconceptions about AR is crucial for accurate diagnosis and treatment. Differentiating between allergies and infections can be challenging due to overlapping symptoms, but allergy testing is instrumental in proper classification.

A prevalent myth is that allergy medications should only be taken when symptoms are present. In reality, proactive medication use can be more effective as allergic inflammation can occur before symptoms emerge, noted Prof Gray.

Furthermore, the belief that using only one brand of allergy medication leads to tolerance build-up lacks evidence. Dispelling these myths can lead to betterinformed treatment decisions and improved patient outcomes, she stressed.

Managing allergic rhinitis

Managing AR involves minimising allergen exposure and utilising pharmacological interventions tailored to individual needs. Intranasal corticosteroids and antihistamines are mainstays in treatment, with newer formulations offering improved efficacy and reduced side effects.

According to Prof Gray, antihistamines capable of inhibiting both histamine and platelet-activating factor hold a theoretical advantage for alleviating allergic AR symptoms, particularly nasal congestion – a

benefit that many antihistamines lack. Furthermore, combination nasal sprays containing intranasal antihistamine corticosteroids offer an advantage by providing multiple benefits in a single device.

Recognising the interconnectedness of AR and asthma and adopting a proactive approach to treatment is essential for optimal disease control.

Conclusion

Comprehensive management of AR requires understanding its pathogenesis, tailoring treatment, and considering the latest advancements in pharmacotherapy. Addressing both symptom relief and underlying inflammation is key to enhancing outcomes and improving patients’ QoL.

To watch a replay of the video, scan the QR code or click here. The webinar is accredited for one (1) CPD point. Once you have watched the video, 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

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§Allergic Rhinitis

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References: 1. South African Medicine Price Registry. Database of Medicine Prices, 01 November 22 [online]. [cited 2022 Nov 17]; Available from URL: http://www.mpr.gov.za/. 2. Marmouz F, Giralt J, Izquierdo I, et al. Morning and evening efficacy evaluation of rupatadine (10 and 20 mg), compared with cetirizine 10 mg in perennial allergic rhinitis: a randomized, double-blind, placebo-controlled trial. J Asthma Allergy 2011;4:27–35. 3. Picado C. Rupatadine: pharmacological profile and its use in the treatment of allergic disorders. Exp Opin Pharmacother. 2006;7(14):1989-2001. 4. Ridolo E, et al. Rupatadine for the treatment of allergic rhinitis and urticaria: a look at the clinical data. Clin Invest 2014;4(5):453-461. 5. Smolensky MH, Lemmer B, Reinberg AE. Chronobiology and chronotherapy of allergic rhinitis and bronchial asthma. Adv Drug Deliv Rev 2007;59:852–882. 6. Alfaro V. Role of histamine and platelet-activating factor in allergic rhinitis. J Physiol Biochem 2004;60(2):101-112. 7. RUPANASE® professional information, 02 October 2014. 8. Steubner P, et al. Effects of rupatadine vs placebo on allergen-induced symptoms in patients exposed to aeroallergens in the Vienna Challenge Chamber. Ann Allergy Asthma Immunol 2006;96:37-44.

Scheduling status: S2 Proprietary name (and dosage form): RUPANASE

This article was independently sourced by Specialist Forum.

Integrating cardio-oncology in prostate cancer care Addressing cardiovascular risks in cancer survivors

Dr Alexander Lyon, a senior lecturer in cardiology at Imperial College London and a consultant cardiologist at the Royal Brompton Hospital, recently hosted a CPD webinar focusing on cardio-oncology. The webinar was chaired by Dr Trishun Singh, Africa’s first certified cardio-oncologist, and founder of the first Cardio-Oncology Centre of Excellence in South Africa. This webinar was sponsored by Astellas Pharma in the interest of education, awareness, and support.

In recent years, we have seen a significant transformation in cancer treatment outcomes. This progress has led to the development of a new field: Cardio-oncology. Cardio-oncology focuses on optimising cardiovascular (CV) health in cancer patients before, during, and after their cancer therapy. This approach is essential because many cancer treatments can have adverse effects (AEs) on the CV system, requiring integrated care between oncologists and cardiologists.

The importance of cardio-oncology becomes evident when considering the survival rates of prostate cancer (PCa) patients. Many men no longer die from PCa but live with it as a controlled, chronic disease. However, some men living with PCa may develop CV diseases, often exacerbated by cancer treatments as mentioned.

Studies have shown that men living with PCa – especially those undergoing androgen deprivation therapy (ADT) – face an increased risk of CVDs, including myocardial infarction (MI), heart failure (HF), and stroke. This risk is particularly pronounced in men with pre-existing CV conditions.

A Swedish study involving 76 000 participants living with PCa, showed that men treated with ADT had a 40% higher risk of CVD than those not on such therapy. This risk translates into an increased incidence

of MI, arrhythmias, ischaemic heart disease, HF, and stroke. The study emphasised that ADT therapy accelerates CV risks through mechanisms such as increased diabetes incidence, hypertension, and prothrombotic effects.

One potential solution to mitigate these CV risks is to consider the type of ADT used. Research has suggested that gonadotropin hormone-releasing hormone (GnRH) antagonists may present a lower CV risk compared to GnRH agonists.

GnRH agonists are known to cause significant metabolic changes. These changes include muscle mass loss, increased abdominal adiposity, and a rise in cholesterol levels, which can contribute to new-onset diabetes and increased CV risk.

The Oral relugolix for AndrogenDeprivation Therapy in Advanced Prostate Cancer study showed that relugolix, a GnRH antagonist, not only maintained effective testosterone suppression but also significantly reduced major adverse cardiac events compared to GnRH agonists.

In response to these findings, the European Society of Cardiology (ESC) has developed guidelines for cardiooncology, emphasising the need for CV risk assessments before starting cancer treatment. These guidelines recommend using 10-year CV risk scores and regular

monitoring of CV health during treatment. For high-risk patients, GnRH antagonists may be preferable, and ongoing assessments of blood pressure (BP), cholesterol, and glucose levels are essential. Primary care physicians and cardiologists play a crucial role in managing the CV health of patients living with PCa. They should educate patients on healthy lifestyles, monitor BP and cholesterol levels, and manage diabetes and hypertension effectively. The integration of cardiooncology into routine cancer care ensures that patients receive comprehensive treatment that addresses their cancer and CV health, improving overall survival and quality of life.

If you missed the webinar, you can access the replay video here or scan the QR code. Once you have finished watching the webinar, send an e-mail to john.woodford@newmedia.co.za to have your CPD point allocated. SF

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