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African countries are preparing to face the outbreak of COVID-19, which the World Health Organization declared a Global Public Health Emergency of International Concern on 31 January 2020 [1] and a pandemic 40 days later. [2] COVID-19 is caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The virus, emerging in early December 2019 in Wuhan, Hubei Province, China, [3] has since spread explosively throughout the world. Most of Europe and the USA has been severely affected in recent weeks despite their relatively high income per capita and robust public healthcare systems. In contrast, African countries are poorly resourced, have a sizeable vulnerable population, and in recent years noticeably demonstrated vulnerability to epidemics. [4] Many South Africans of all ages have significant risk factors for severe COVID-19 outcomes. The pre-existing colliding epidemics of HIV infection and tuberculosis (TB), as well as the high prevalence of non-communicable diseases such as hypertension, diabetes and cardiovascular disease, place a large segment of the population at high risk. [5] This open-access article is distributed under Creative Commons licence CC-BY-NC 4.0.

Real-world evidence (RWE) is derived from real-world data (RWD) sources including electronic health records, claims data, registries (disease, product) and pragmatic clinical trials. The importance of RWE derived from RWD has been once again demonstrated during the coronavirus disease 2019 (COVID-19) pandemic, as it can improve patient care by complementing information obtained from traditional clinical trial programs. Additionally, RWE can generate insights into disease mechanisms, epidemiology, patient flows in and out of healthcare systems, and drivers and barriers to optimal clinical care in realworld settings. Identifying unmet medical needs is crucial as it often can inform which investigational new drugs enter clinical trial testing, and RWE studies from hospital settings have contributed substantial progress here. RWE can also optimize the design of clinical studies, inform benefit risk assessments and use networks of pragmatic studies to help with clinical trial feasibilities and eventual trial initiation. The challenges of RWD include data quality, reproducibility and accuracy which may affect validity. RWD

Background: Proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors are a novel class of non-statin lipid lowering therapy that reduce LDL-cholesterol by 50 - 60%. PCSK9 inhibitors decrease LDL-cholesterol by preventing intracellular degradation of LDL receptors; subsequently, a greater number of LDL-receptors are available on the cell surface to extract circulating LDL. Objective: To describe the origins of PCSK9 inhibitors and their current use in clinical practice. Methods: We performed a narrative review of the PCSK9 inhibitor class of drugs. Results: Current data indicate that PCSK9 inhibitors effectively reduce LDL-cholesterol and are well tolerated and safe. PCSK9 inhibitors have also been shown to reduce cardiovascular event rates in patients with stable atherosclerotic cardiovascular disease and in patients with a recent (up to one year) acute coronary syndrome. Given the costs, chronicity of the treatment and the potential budget impact, PCSK9 inhibitors are often limited to patients with the highest absolute risk for major adverse cardiovascular events despite optimal treatment with high-intensity statin and ezetimibe. Conclusion: PCSK9 inhibitors have a favorable safety, efficacy and tolerability profile. Postmarketing safety surveillance and real-world studies are needed to further support the long-term safety profile of this class of medicine.

Lupus myocarditis (LM) is a potentially fatal manifestation of systemic lupus erythematosus (SLE), occurring in 5–10% of patients. Clinical manifestations may vary from an unexplained tachycardia to fulminant congestive cardiac failure (CCF). With no single clinical or imaging modality being diagnostic, a rational and practical approach to the patient presenting with possible LM is essential. Markers of myocyte injury (including troponin-I and creatine kinase) may be unelevated and do not exclude a diagnosis of LM. Findings on electrocardiogram are non-specific but remain essential to exclude other causes of CCF such as an acute coronary syndrome or conduction disorders. Echocardiographic modalities including wall motion abnormalities and speckle tracking echocardiography may demonstrate regional and/or global left ventricular dysfunction and is more sensitive than conventional echocardiography, especially early in the course of LM. Cardiac magnetic resonance imaging (CMR) is regarded as the non-invasive diagnostic modality of choice in myocarditis. Whilst more sensitive and specific than echocardiography, CMR has certain limitations in the context of SLE including technical challenges in acutely unwell and uncooperative patients, contra-indications to gadolinium use in the context of renal impairment (including lupus nephritis) and limited literature regarding the application of recommended diagnostic CMR criteria in SLE. Both echocardiography as well as CMR may detect subclinical myocardial dysfunction and/or injury of which the clinical significance remains uncertain. Considering these challenges, a combined decision-making approach by rheumatologist and cardiologist, interpreting diagnostic test results within the clinical context of the patient is essential to ensure an accurate, early diagnosis of LM.

Tuberculosis affects 10 million people and over 320,000 South Africans every year. A significant proportion of patients treated for tuberculosis develop post-tuberculous lung disease (PTBLD), a disease of chronic respiratory impairment for which there is a lack of affordable treatment options.PTBLD a heterogenous disorder that shares phenotypical features with chronic obstructive lung disease, bronchiectasis, lung fibrosis and destruction as well as pulmonary hypertension. There remains a paucity of proven pharmacotherapy for the management of PTBLD. Theophylline, a widely available and affordable medicine that has largely fell out of favour in high-income settings due to its toxicity and narrow therapeutic index, may be repositioned for the treatment of PTBLD. In this review, we unpack the potential role of theophylline in the management of PTBLD by reviewing the evidence for its bronchodilatory, antiinflammatory and potential pleotrophic effects.

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