Atypical presentation of a posterior fossa tumour: A case report.

BACKGROUND: We described a case of a patient with a meningioma in the posterior fossa presenting atypically with an isolated unilateral vocal cord palsy causing severe respiratory distress. This is of interest as the patient had no other symptomatology, especially given the size of the mass, which would typically cause a pressure effect leading to neurological and auditory symptoms. CASE SUMMARY: This case report described a 48-year-old male who was married with two children and employed as a car guard. He had a medical history of asthma for the past 10 years controlled with an as-needed beta 2 agonist metered dose inhaler. He initially presented to our facility with severe respiratory distress. He reported a 1-wk history of shortness of breath and wheezing that was not relieved by his bronchodilator. He had no constitutional symptoms or impairment of hearing. On clinical examination, the patient's chest was "silent." Our initial assessment was status asthmaticus with type 2 respiratory failure, based on the history of asthma, a "silent chest," and the arterial blood gas results. CONCLUSION: A posterior fossa meningioma of such a large size and with extensive infiltration rarely presents with an isolated unilateral vocal cord palsy. The patient's chief presenting feature was severe respiratory distress, which combined with his background medical history of asthma, was misleading. Clinicians should thus consider meningioma as a differential diagnosis for a unilateral vocal cord palsy even without audiology involvement.

Access to novel anti-diabetic agents in resource limited settings: A brief commentary.

The prevalence of diabetes mellitus is increasing in resource limited settings. Simultaneously, there has been an increase in the number of novel therapies for the management of diabetes mellitus. However, use of novel antidiabetic therapies is limited because of major market access challenges in resource limited settings. Niching products to those patients with the highest absolute risk for major adverse cardiovascular outcomes, and thus most likely to benefit from the therapy, are less likely to have negative budget impact for funders. To improve access, and reduce morbidity and mortality, requires alignment amongst key stakeholders including patient advocacy groups, health care professional councils, national departments of health, the pharmaceutical industry, treasury and finance departments.

Multiple fusiform and saccular aneurysms in a person living with Human Immunodeficiency Virus.

Cerebral aneurysms secondary to human immunodeficiency virus vasculopathy are a diagnosis by exclusion and its mechanism is unknown. We report on a 21-year-old male with human immunodeficiency virus infection and suboptimal virological control, despite highly active antiretroviral therapy. An incidental discovery of multiple cerebral aneurysms occurred in this patient, who initially presented with signs of disorientation, acute psychosis, and a history of blunt cranial trauma. A non-contrasted computerized tomography scan of the encephalon showed no intracranial hemorrhage but multiple cerebral (saccular and fusiform) aneurysms. Subsequently, a non-urgent computerized tomography angiogram of the cerebral vasculature corroborated the existence of multiple cerebral aneurysms. Despite investigation, no secondary etiological factors for the aneurysmal condition were identified. The multitude of cerebral aneurysms was consequently ascribed to human immunodeficiency virus-associated vasculopathy. The patient was managed conservatively. At discharge, he was lucid and apsychotic. A unique aspect of the case is the presence of both fusiform and saccular cerebral aneurysms.

Health Care Resource Utilization in Adults Living With Type 1 Diabetes Mellitus in the South African Public Health Sector: Protocol for a 1-Year Retrospective Analysis With a 5-, 10-, and 25-Year Projection.

BACKGROUND: Type 1 diabetes mellitus (T1DM) is less common than type 2 diabetes mellitus but is increasing in frequency in South Africa. It tends to affect younger individuals, and upon diagnosis, exogenous insulin is essential for survival. In South Africa, the health care system is divided into private and public health care systems. The private system is well resourced, whereas the public sector, which treats more than 80% of the population, has minimal resources. There are currently no studies in South Africa, and Africa at large, that have evaluated the immediate and long-term costs of managing people living with T1DM in the public sector. OBJECTIVE: The primary objective was to quantify the cost of health care resource utilization over a 12-month period in patients with controlled and uncontrolled T1DM in the public health care sector. In addition, we will project costs for 5, 10, and 25 years and determine if there are cost differences in managing subsets of patients who achieve glycemic control (hemoglobin A1c [HbA1c] <7%) and those who do not. METHODS: The study was performed in accordance with Good Epidemiological Practice. Ethical clearance and institutional permissions were acquired. Clinical data were collected from 2 tertiary hospitals in South Africa. Patients with T1DM, who provided written informed consent, and who satisfied the inclusion criteria were enrolled in the study. Data collection included demographic and clinical characteristics, acute and chronic complications, hospital admissions, and so on. We plan to perform a cost-effectiveness analysis to quantify the costs of health care utilization in the preceding 12 months. In addition, we will estimate projected costs over the next 10 years, assuming that study participants maintain their current HbA1c level. The cost-effectiveness analysis will be modeled using the IQVIA CORE Diabetes Model. The primary outcome measures are incremental quality-adjusted life years, incremental costs, incremental cost-effectiveness ratios, and incremental life years. RESULTS: Ethical clearance and institutional approval were obtained (reference number 200407). Enrollment began on February 9, 2021, and was completed on August 24, 2021, with 224 participants. A database lock was performed on October 29, 2021. The statistical analysis and clinical study report were completed in January 2022. CONCLUSIONS: At present, there are no data assessing the short- and long-term costs of managing patients with T1DM in the South African public sector. It is hoped that the findings of this study will help policy makers optimally use limited resources to reduce morbidity and mortality in people living with T1DM. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/44308.

Optimal dosing of gliclazide-A model-based approach.

Gliclazide was approved as a treatment for type 2 diabetes in an era before model-based drug development, and consequently, the recommended doses were not optimised with modern methods. To investigate various dosing regimens of gliclazide, we used publicly available data to characterise the dose-response relationship using pharmacometric models. A literature search identified 21 published gliclazide pharmacokinetic (PK) studies with full profiles. These were digitised, and a PK model was developed for immediate- (IR) and modified-release (MR) formulations. Data from a gliclazide dose-ranging study of postprandial glucose were used to characterise the concentration-response relationship using the integrated glucose-insulin model. Simulations from the full model showed that the maximum effect was 44% of the patients achieving HbA1c <7%, with 11% experiencing glucose <3 mmol/L and the most sensitive patients (i.e., 5% most extreme) experiencing 35 min of hypoglycaemia. Simulations revealed that the recommended IR dose (320 mg) was appropriate with no efficacy gain with increased dose. However, the recommended dose for the MR formulation may be increased to 270 mg, with more patients achieving HbA1c goals (i.e., HbA1c <7%) without a hypoglycaemic risk higher than the resulting risk from the recommended IR dose.

Healthcare Resource Utilization in Controlled Versus Uncontrolled Adults Living With Type 1 Diabetes in the South African Public Healthcare Sector.

OBJECTIVES: This study aimed to understand the cost implications of managing people living with type 1 diabetes mellitus in the South African public healthcare system. METHODS: A multicenter, noninterventional retrospective chart review study was performed. Data on healthcare resource consumption, demographics, risk factors, clinical history, and acute events were collected. Direct medical costs were collected over a 1-year period, stratified by controlled versus uncontrolled patients. In addition, the costs in people with controlled (glycated hemoglobin < 7%) versus uncontrolled glycated hemoglobin (≥ 7%) at time horizons of 1, 5, 10, and 25 years were modeled using the IQVIA Core Diabetes Model. RESULTS: The costs based on the retrospective chart review were $630 versus $1012 (controlled versus uncontrolled population). The modeled costs at various time horizons were as follows: at 1 year, $900 versus $1331; at 5 years, $4163 versus $6423; at 10 years, $7759 versus $16 481; and at 25 years, $16 969 versus $66 268. The largest cost in the controlled population was severe hypoglycemia requiring nonmedical assistance, severe hypoglycemia requiring medical assistance, and treatment costs. In the uncontrolled population, the largest cost was the cost of diabetic ketoacidosis, severe hypoglycemia requiring nonmedical assistance, severe hypoglycemia requiring medical assistance, and foot complications. CONCLUSIONS: Strict glycemic control reduces healthcare resource use overall. Patients in the controlled group still experienced high resource use related to hypoglycemic events. The introduction of a structured patient education program and analog insulins may result in less episodes of hypoglycemia and potential cost savings.

Post-tuberculous lung disease: should we be using Theophylline?

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, anti-inflammatory and potential pleotrophic effects.

Real-world evidence and product development: Opportunities, challenges and risk mitigation.

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 real-world 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 and RWE must be fit for purpose and one must be cognizant of inherent biases.

Safety and Efficacy of Enoxaparin in Pregnancy: A Systematic Review and Meta-Analysis.

INTRODUCTION: International guidelines support the use of low molecular weight heparins for the treatment of thromboembolism and thromboprophylaxis during pregnancy. However, evidence of the benefit and harm associated with specific low molecular weight heparins such as enoxaparin is dated. No current systematic review and meta-analysis describing the safety and efficacy of enoxaparin for thromboembolism and thromboprophylaxis during pregnancy exists. METHODS: PubMed, Embase, and Cochrane databases were searched on August 17, 2018 for clinical trials or observational studies in pregnant women receiving enoxaparin; patients with a prosthetic heart valve were excluded. Risk ratios (RR) with 95% confidence intervals (CI) were calculated using a random effects model, and heterogeneity was measured using the I2 statistic. RESULTS: Of the 485 records identified in the search, 24 studies published clinical trials, and observational studies were found dating back to 2000. Only one observational cohort and one randomized control trial focused on the use of enoxaparin for thromboprophylaxis and therefore efficacy was not assessed; the other studies included women with recurrent pregnancy loss (15 studies), history of placental vascular complications (five studies), and recurrent in vitro fertilization failure (two studies) and were therefore analyzed in terms of safety only. Bleeding events were non-significantly more often reported for enoxaparin compared to untreated controls (RR 1.35 [0.88-2.07]) but less often reported for enoxaparin versus aspirin (RR 0.93 [0.62-1.39]); thromboembolic events, thrombocytopenia, and teratogenicity were rarely reported events; in patients with a history of recurrent pregnancy loss, encouragingly the rates of pregnancy loss were significantly lower for enoxaparin compared to untreated controls (RR 0.58 [0.34-0.96]) and enoxaparin + aspirin versus aspirin alone (RR 0.42 [0.32-0.56]) as well as observably lower for enoxaparin versus aspirin alone (RR 0.39 [0.15-1.01]), though significant heterogeneity was observed (I2 > 60). CONCLUSION: Literature on the efficacy and safety of enoxaparin for thromboembolism and thromboprophylaxis remains scanty, and therefore efficacy was not assessed; in terms of safety, when including other indications for enoxaparin in pregnancy, we found that enoxaparin was associated with significantly lower complications than aspirin. Given differences in study design and study heterogeneity, pregnancy loss results should be interpreted with caution. Moreover, reports of thromboembolic events, thrombocytopenia, and congenital malformations were rare. FUNDING: Sanofi.

The therapeutic management of South African dyslipidaemic patients at very high cardiovascular risk (CARDIO TRACK): a cross-sectional study.

BACKGROUND: Dyslipidaemia is a major modifiable risk factor for atherosclerotic cardiovascular disease. At the time the study was conducted, guidelines recommended a low-density lipoprotein cholesterol (LDL-C) target of less than 1.8 mmol/l and a reduction of at least 50% if the baseline LDL-C was between 1.8 and 3.5 mmol/l in patients with either very high cardiovascular risk or established atherosclerosis. In South Africa, there is a paucity of data on attainment of LDL-C goal in patients with very high cardiovascular risk who are on maximum tolerated statin with or without ezetimibe. OBJECTIVE: The aim was to assess the percentage of very high cardiovascular risk South African patients with dyslipidaemia not reaching an LDL-C goal of less than 1.8 mmol/l, despite maximum tolerated statin with or without ezetimibe. METHODS: This was a multi-centre, observational, cross-sectional study conducted at 15 private healthcare sector sites and one public sector site. Adults (> 18 years) with very high cardiovascular risk of familial hypercholesterolaemia receiving stable, maximum-tolerated statin therapy for at least four weeks prior to their latest lipid profile were enrolled into the study, and electronic case report forms were completed after written informed consent was provided. LDL-C goal attainment was modelled, first assuming an increase in the statin dose to the registered maximum, followed by the addition of ezetimibe or a PCSK9-inhibitor. RESULTS: In total, 507 patients were screened, of whom 492 were eligible for study participation. One patient was excluded from the analysis because of a missing LDL-C value. Most participants were male (male 329, 67%; female 162, 33%). Most patients were either obese (223, 46.0%) or overweight (176, 36.3%). Hypertension and diabetes mellitus were frequent co-morbidities and were found in 381 (77.6%) and 316 (64.4%) patients, respectively. Eighty (16.3%) patients reported current smoking. Only 68 (13.8%) patients were taking ezetimibe in addition to a statin. Reasons for not using ezetimibe included no requirement for ezetimibe in the opinion of the treating physician (229, 48.7%), cost (149, 31.7%), Physician's choice (39, 8.3%), or other (53, 11.3%). Only 161 (32.8%) of the patients attained their goal LDL-C level. In our modelling analysis, increasing the statin dose to the registered maximum and adding ezetimibe brought an additional 34.5% of patients to goal, while adding a PCSK9-inhibitor, irrespective of any other changes to lipid-lowering therapy brought over 90% of not-at-goal patients to goal. CONCLUSIONS: Most study participants were not at LDL-C goal despite maximum-tolerated statin, highlighting the need for treatment intensification in this high-risk population. Although intensifying treatment by adding a PCSK9-inhibitor brought more patients to goal, the initial addition of ezetimibe would be more reasonable, given the cost of PCSK9-inhibitors.

Management of adult patients with type 1 diabetes mellitus in Africa: A post-hoc cohort analysis of 12 African countries participating in the International Diabetes Management Practices Study (Wave 7).

There is a paucity of information on real world management of African adult patients with type 1 diabetes mellitus (T1DM). We aimed to describe a cohort of African adults with T1DM.The International Diabetes Management Practices Study is an observational survey conducted from 2005 to 2017. Data were collected in seven individual waves from countries in Asia, Africa, East Europe, and Latin America. Wave 7 was conducted from 2016 to 2017 and the African cohort included 12 countries. Questionnaires were administered to clinicians and patients. Analyses were mainly descriptive. Logistic regressions were performed to identify predictive factors for glycaemic control.A total of 788 patients were enrolled in the study. HbA1c values were available for 712 patients; only 16.6% had HbA1c values <7%. A total of 196 (24.9%) reported being hospitalized in the preceding year, with the most common reasons being diabetic ketoacidosis (58.1%, 93/160) and hypoglycaemia (31.1%; 52/167). Over half of the patients (55.4%) stated that the cost of test strips limited regular glycemic monitoring; a minority of patients (15%, 120/788) received structured diabetes education. Predictors of HbA1c <7% included patients receiving diabetes education (odds ratio [OR] [95% confidence interval, CI] = 2.707 [1.157-6.335] P = .022), following a healthy diet and exercise plan (OR [95% CI] = 2.253 [1.206-4.209], P < .001) and self-managing (monitoring glucose levels and adjusting insulin accordingly) (OR [95% CI] 2.508 [1.500-4.191] P < .001).African adults with T1DM have suboptimal glycemic control with almost one-quarter reporting hospitalization within the preceding year. Most patients felt comfortable with self-adjustment of insulin dose but said that the cost of test strips was the main factor that limited regular monitoring. Reducing direct costs of testing strips and insulin, and improving education will address major challenges within these settings.

PCSK9 Inhibitors: From Nature's Lessons to Clinical Utility.

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.

Management of low-density lipoprotein cholesterol levels in South Africa: the International ChoLesterol management Practice Study (ICLPS).

The International Cholesterol Management Practice Study (ICLPS) South Africa investigated achievement of European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) guideline low-density lipoprotein cholesterol (LDL-C) targets in real-world clinical practice. Demographic data, clinical characteristics, cardiovascular risk factors, lipid-modifying medications, lipid values and investigator's assessment of cardiovascular risk were recorded for 396 patients on stable lipid-modifying therapy. Most (98.7%) patients received statins; 25.1% of statin-treated patients were receiving high-intensity statins. Overall, 41.4% of patients achieved their LDL-C target; among 354 (89.4%) patients in whom cardiovascular disease risk, based on ESC Systematic Coronary Risk Estimation (SCORE) was calculated, achievement rate was 14.3% for moderate-risk (n = 7), 59.3% for high-risk (n = 123) and 32.3% for very high-risk patients (n = 223). Half of Asian (54.7%) and black African (53.2%) patients were at LDL-C target compared with 29.8% of European/Caucasian and 27.3% of 'other' patients. Improved guideline adherence and greater use of combination therapy may increase LDL-C goal achievement.

Does the use of adjunct urine lipopolysaccharide lipoarabinomannan in HIV-infected hospitalized patients reduce the utilization of healthcare resources? A post hoc analysis of the LAM multi-country randomized controlled trial.

BACKGROUND: The World Health Organization (WHO) recommends the use of adjunctive urine lipopolysaccharide lipoarabinomannan (LAM) testing in hospitalized HIV-infected persons with suspected tuberculosis (TB) and a CD4 count <100cells/ml. However, the recommendation is conditional, and uptake by individual treatment programmes depends on perceived additional benefit. The aim of this study was to determine whether adjunctive LAM testing has additional clinical benefits including a reduction in healthcare-related use of resources. METHODS: A post hoc analysis was performed of a published multicentre, multi-country, randomized controlled trial that showed an approximate 20% mortality benefit in HIV-infected hospitalized patients who underwent adjunctive LAM testing as part of their diagnostic workup. In that parent study, adult HIV-infected hospitalized patients with suspected TB (n=2528) were randomly allocated to either routine diagnostics (smear microscopy, Xpert MTB/RIF, and culture; n=1271), or routine diagnostics plus adjunctive urine LAM testing (n=1257). Data were further analyzed to determine whether there were other potential benefits of LAM usage based on CD4 count and illness severity. Aspects evaluated included: (1) the reduction in number of diagnostic sputum samples tested, (2) the utilization of additional imaging, (3) disease resolution based on follow-up signs and symptoms of illness severity, and (4) the reduction in hospital readmission. RESULTS: Adjuvant LAM did not reduce the number of diagnostic sputum samples requested, the need for additional imaging, or the hospital readmission rate. However, adjunctive LAM was associated with a more rapid rate of disease resolution (dyspnoea) in the severely ill subgroup. Higher LAM grade (grades 4 and 5), compared to lower grade positivity (≤3), was associated with lower use of ultrasound, lower Karnofsky performance score, lower CD4 cell count, and shorter time to culture positivity. CONCLUSIONS: Although, adjunct LAM was associated with a mortality benefit in the parent study, no benefit could be demonstrated in the secondary analysis with respect to the number of diagnostic sputum samples requested, the use of additional imaging, or hospital readmission rates. However, given the limitations of the present study, further appropriately designed studies are required to determine the effect of adjunct urine LAM on the utilization of healthcare resources.

Medical Science Liaisons (MSL) in Africa: a perspective.

The role of a Medical Science Liaison (MSL) is of growing importance to pharmaceutical, biotechnology, diagnostic and medical device companies. Through scientific engagement MSLs add value to clinical practice, ultimately benefiting patients. The MSL role is dynamic and encompasses in-depth product and disease knowledge together with the ability to communicate relevant, unbiased scientific information concisely and timely. Tasks are focused on contributing towards the advancement of medical knowledge, scientific data generation and dissemination. Professional relationships are developed, fostering collaboration between external experts and typically the medical affairs departments of pharmaceutical companies through a credible liaison. Through such relationships, critical insights are shared that shape the development pipeline, promote successful clinical translation and guide the market deployment strategy of therapeutic interventions through-out their life cycle. Despite the rising number of MSLs in the field and the implicit medical value of the role, there remains a lack of understanding for what the roles of a MSL entails. In Africa, where exponential growth of the pharmaceutical industry is expected, the number of MSLs will increase rapidly. Given the complexities of the African continent, the MSLs in this burgeoning environment will face various challenges including remote locations, time-constraints, regulatory and bureaucratic hurdles and importantly physician misperception of the MSL role that collectively may thwart the goal of meaningful scientific engagement; but these challenges can be surmounted through astute proactive planning and utilization of opportunities including digital communication strategies.

Long-term safety and efficacy of alirocumab in South African patients with heterozygous familial hypercholesterolaemia: the ODYSSEY Open-Label Extension study.

BACKGROUND: Alirocumab reduces low-density lipoprotein cholesterol (LDL-C) levels by up to 61%. The ODYSSEY Open-Label Extension study investigated the effect of alirocumab in patients with heterozygous familial hypercholesterolaemia (HeFH) over 144 weeks. METHODS: Eligible patients with HeFH had completed an earlier double-blind, randomised, placebo-controlled parent study. Patients were initiated on 75 mg alirocumab Q2W subcutaneous (SC) unless baseline LDL-C was > 8.9 mmol/l, in which case they received 150 mg alirocumab Q2W. Dose titration to 150 mg Q2W was at the investigator's discretion. RESULTS: The study enrolled 167 patients and the parent study mean (± SD) baseline LDL-C level was 3.65 ± 1.9 mmol/l. Mean LDL-C level was reduced by 48.7% at week 144; mean on-treatment LDL-C was 2.30 ± 1.24 mmol/l. Eight patients reported injection-site reactions, with one treatment discontinuation. Treatment emergent anti-drug antibodies were identified in five patients but these did not affect the efficacy. CONCLUSIONS: Alirocumab effectively and safely reduced LDL-C in these patients.

Viscosupplementation for knee osteoarthritis: a focus on Hylan G-F 20.

Knee osteoarthritis is a chronic degenerative joint disease characterized by destruction of articular cartilage with resultant para-articular bone changes. It is a major cause of disability in older persons and is managed by surgical and nonsurgical interventions. Pharmacotherapy includes acetaminophen, nonsteroidal anti-inflammatory agents, and intra-articular steroids. Another treatment option is viscosupplementation with intra-articular injection of hyaluronan (HA). The full mechanism of action of exogenous HA is uncertain, but studies indicate that it may promote endogenous HA production, reduce inflammation, prevent degeneration of cartilage and promote cartilage regeneration. Clinically, HA may improve symptoms of osteoarthritis and delay time to total knee replacement surgery. However, clinical studies are heterogenous and of varying quality, and thus there is a need for more robust studies to determine the place of viscosupplementation in the management of knee osteoarthritis.

Paraoxonase (PON)-1: a brief overview on genetics, structure, polymorphisms and clinical relevance.

Paraoxonase-1 (PON1) is a high-density lipoprotein-associated esterase and is speculated to play a role in several human diseases including diabetes mellitus and atherosclerosis. Low PON1 activity has been associated with increased risk of major cardiovascular events, therefore a variety of studies have been conducted to establish the cardioprotective properties and clinical relevance of PON1. The major aim of this review was to highlight the important studies and to subsequently assess if PON1 has clinical relevance. A review of the literature showed that there is currently insufficient data to suggest that PON1 has clinical relevance. It is our opinion that robust studies are required to clarify the clinical relevance of PON1.

Therapeutic Management of Dyslipidemia Patients at Very High Cardiovascular Risk (CARDIO TRACK): Protocol for the Observational Registry Study.

BACKGROUND: Dyslipidemia is a major modifiable risk factor for atherosclerotic cardiovascular disease. Current South African guidelines recommend titrating lipid-lowering therapy (LLT) to low-density lipoprotein cholesterol (LDL-C) targets stratified by cardiovascular risk. The LDL-C goal for very high-risk patients is <1.8 mmol/L. In international studies, approximately 30% of patients do not achieve this goal despite receiving maximally tolerated statin doses. There is, however, a paucity of data on LDL-C goal achievement in very high-risk South African patients receiving maximal statin doses. OBJECTIVE: The goal of the research it to assess LDL-C goal achievement in, and clinical characteristics of, very high cardiovascular risk dyslipidemic patients receiving maximal tolerated statin doses with or without ezetimibe. METHODS: This is an observational, cross-sectional South African registry study that plans to include up to 30 sites and 500 study participants. Adult patients with very high cardiovascular risk status receiving stable, maximally tolerated statin doses (with or without ezetimibe) will be eligible for inclusion. RESULTS: Funding has been awarded and enrollment began on November 15, 2017, and was completed on April 13, 2018, with 507 participants. Database lock was done on June 21, 2018. The statistical analysis has commenced and we expect the final clinical study report to be completed by October 2018. CONCLUSIONS: This study will document the adequacy of LLT in those at highest risk and will thus fill an important data gap in South Africa. This data may be useful in assessing the need for novel LLTs like proprotein convertase subtilisin/kexin 9 inhibitors that substantially lower cholesterol levels in addition to optimal statin therapy. REGISTERED REPORT IDENTIFIER: RR1-10.2196/9248.