Rheumatic heart disease (RHD) is a neglected disease affecting 33 million people, mainly in low and middle income countries. Yet very few large trials or registries have been conducted in this ...population. The INVICTUS program of research in RHD consists of a randomized-controlled trial (RCT) of 4500 patients comparing rivaroxaban with vitamin K antagonists (VKA) in patients with RHD and atrial fibrillation (AF), a registry of 17,000 patients to document the contemporary clinical course of patients with RHD, including a focused sub-study on pregnant women with RHD within the registry. This paper describes the rationale, design, organization and baseline characteristics of the RCT and a summary of the design of the registry and its sub-study. Patients with RHD and AF are considered to be at high risk of embolic strokes, and oral anticoagulation with VKAs is recommended for stroke prevention. But the quality of anticoagulation with VKA is poor in developing countries. A drug which does not require monitoring, and which is safe and effective for preventing stroke in patients with valvular AF, would fulfill a major unmet need.
The INVestIgation of rheumatiC AF Treatment Using VKAs, rivaroxaban or aspirin Studies (INVICTUS-VKA) trial is an international, multicentre, randomized, open-label, parallel group trial, testing whether rivaroxaban 20 mg given once daily is non-inferior (or superior) to VKA in patients with RHD, AF, and an elevated risk of stroke (mitral stenosis with valve area ≤2 cm2, left atrial spontaneous echo-contrast or thrombus, or a CHA2DS2VASc score ≥2). The primary efficacy outcome is a composite of stroke or systemic embolism and the primary safety outcome is the occurrence of major bleeding. The trial has enrolled 4565 patients from 138 sites in 23 countries from Africa, Asia and South America. The Registry plans to enroll an additional 17,000 patients with RHD and document their treatments, and their clinical course for at least 2 years. The pregnancy sub-study will document the clinical course of pregnant women with RHD.
INVICTUS is the largest program of clinical research focused on a neglected cardiovascular disease and will provide new information on the clinical course of patients with RHD, and approaches to anticoagulation in those with concomitant AF.
Phenolic compounds are natural substances that can be obtained from plants. Many of them are potent growth inhibitors of foodborne pathogenic microorganisms, however, phenolic activities against ...spoilage yeasts are rarely studied. In this study, planktonic and biofilm growth, and the adhesion capacity of Pichia anomala, Saccharomyces cerevisiae, Schizosaccharomyces pombe and Debaryomyces hansenii spoilage yeasts were investigated in the presence of hydroxybenzoic acid, hydroxycinnamic acid, stilbene, flavonoid and phenolic aldehyde compounds. The results showed significant anti-yeast properties for many phenolics. Among the tested molecules, cinnamic acid and vanillin exhibited the highest antimicrobial activity with minimum inhibitory concentration (MIC) values from 500 µg/mL to 2 mg/mL. Quercetin, (−)-epicatechin, resveratrol, 4-hydroxybenzaldehyde, p-coumaric acid and ferulic acid were also efficient growth inhibitors for certain yeasts with a MIC of 2 mg/mL. The D. hansenii, P. anomala and S. pombe biofilms were the most sensitive to the phenolics, while the S. cerevisiae biofilm was quite resistant against the activity of the compounds. Fluorescence microscopy revealed disrupted biofilm matrix on glass surfaces in the presence of certain phenolics. Highest antiadhesion activity was registered for cinnamic acid with inhibition effects between 48% and 91%. The active phenolics can be natural interventions against food-contaminating yeasts in future preservative developments.
Natural compounds are a suitable alternative to synthetic food preservatives due to their natural origin and health-promoting properties. In the current study, phenolic-phenolic and ...phenolic-synthetic combinations were tested for their antibiofilm formation, anti-planktonic growth, and anti-adhesion properties against
,
(formerly
),
, and
. The phenolics were vanillin and cinnamic acid, while the synthetic preservatives were sodium benzoate, potassium sorbate, and sodium diacetate. The vanillin-cinnamic acid combination had synergistic effect in all the tested yeasts for the biofilm inhibition with a fractional inhibitory concentration index (FICI) of ≤0.19 for
, 0.25 for
, 0.31 for
.
, and 0.5 for
. Most of the phenolic-synthetic combinations had indifferent interaction regarding biofilm formation. The vanillin-cinnamic acid combination also had higher activity against spoilage yeasts adhesion on the abiotic surface and planktonic growth compared to the phenolic-synthetic combinations. For the phenolic-synthetic anti-planktonic activity, synergistic interaction was present in all the vanillin-synthetic combinations in
, vanillin-sodium benzoate and vanillin-potassium sorbate in
, vanillin-sodium benzoate in
, and cinnamic acid-sodium diacetate in
. These results suggest a novel antimicrobial strategy that may broaden the antimicrobial spectrum and reduce compound toxicity against food spoilage yeasts.
Background: Acute coronary syndrome (ACS) is understudied in sub-Saharan Africa despite its increasing disease burden. We sought to create an ACS registry at Kenyatta National Hospital to evaluate ...the presentation, management and outcomes of ACS patients. Methods: From November 2016 to April 2017, we conducted a retrospective review of ACS cases managed at Kenyatta National Hospital between 2013 and 2016, with a primary discharge diagnosis of ACS, based on International Classification of Diseases (ICD) 10 coding (I20-I24). We compared the presentation, management and outcomes by ACS subtype using analysis of variance testing. We created multivariable logistic regression models using the Global Registry of Acute Coronary Events (GRACE) risk score to evaluate the association between clinical variables, including guideline-directed medical therapy and in-hospital outcomes. Results: Among 196 ACS admissions, the majority (65%) was male, and the median age was 58 years. Most (57%) ACS admissions were for ST-segment-elevation myocardial infarction (STEMI). In-hospital dual antiplatelet (> 85%), beta-blockade (72%) and anticoagulant (72%) therapy was common. A minority (33%) of patients with STEMI was eligible for reperfusion therapy but only 5% received reperfusion. In-hospital mortality rate was 17%, and highest among individuals presenting with STEMI (21%). After multivariable adjustment, higher serum creatinine level was associated with higher odds of in-hospital death (OR = 1.84, 95% CI: 1.21– 2.78), and STEMI and Killip class > 1 were associated with in-hospital composite of death, re-infarction, stroke, major bleeding or cardiac arrest (STEMI: OR = 8.70, 95% CI: 2.52–29.93; Killip > 1: OR = 10.7, 95% CI: 3.34–34.6). Conclusions: We describe the largest ACS registry at Kenyatta National Hospital to date and identify potential areas for improved ACS care related to diagnostics and management to optimise in-hospital outcomes.
Abstract
Elevated blood pressure (BP) is the leading cause of global mortality, but control rates remain poor because most patients, especially in Africa, are unaware. May Measurement Month (MMM) is ...an annual global BP screening campaign that was initiated by the International Society of Hypertension (ISH) in 2017 to raise awareness of raised BP. Following participation in 2017 and 2018, Kenya participated again in 2019 and the results are reported here. Screening was carried out in 30 sites by volunteers coordinated by the Kenya Cardiac Society. Participants had three BP readings by standard methods with the last two being averaged and recorded. Heart rate, weight, height, socio-demographic parameters, and co-morbidities were documented. Hypertension was defined as a systolic BP (SBP) ≥140 mmHg and/or a diastolic BP (DBP) ≥90 mmHg or being on treatment with at least one antihypertensive medication. A total of 33 992 participants were screened, mean age was 42.5 (SD 16.8) years and 58.7% of participants were female. Only 27.3% had their BPs checked within the preceding 12 months. After multiple imputation, 26.1% were hypertensive, of whom 34.5% were aware of their hypertension and 31.5% were on treatment. Of those on treatment, 59.7% were controlled translating to 18.8% of all hypertensives. Being on treatment for hypertension, overweight, obese or having had hypertension in previous pregnancy were associated with increased SBP and DBP, while diabetes was associated with raised SBP. Two-thirds of hypertensives were unaware. Only a third of those aware were on treatment, with about 60% of these controlled. Lack of awareness remains a significant barrier to BP control. Programmes to raise awareness such as MMM are significant in raising population awareness.
Elevated blood pressure (BP) is a growing burden worldwide leading to over 10 million deaths each year. Sub-Saharan Africa has the highest age-adjusted prevalence of hypertension. In Kenya, 24.5% of ...adults have elevated BP with lack of awareness being the main barrier to achieving satisfactory control rates. May Measurement Month (MMM17) is a global initiative aimed at raising awareness of high BP and to act as a temporary solution to the lack of screening programmes worldwide. An opportunistic cross-sectional survey of volunteers aged ≥18 years was carried out in May 2017. Screening was coordinated by the Kenya Cardiac Society in 17 sites across the country. Blood pressure measurements, the definition of hypertension and statistical analysis followed the standard MMM protocol. A total of 14 847 individuals were screened. After multiple imputation, 3647 (24.6%) had hypertension. Of individuals not receiving any antihypertensive medication, 2019 (15.3%) were hypertensive. Of individuals receiving antihypertensive medication, 740 (45.5%) had uncontrolled BP. Being diabetic and having a body mass index (BMI) ≥25 kg/m
were associated with higher BP. Lack of awareness and poor control in those identified is a major challenge in Kenya. The MMM project demonstrated that mass screening for elevated BP is feasible, even in settings with limited resources. The presence of hypertension in a quarter of Kenyan adults with poor awareness and control rates demonstrates the need for programmes to raise awareness in the community.
Abstract
Hypertension (HTN) is highly prevalent and the leading cardiovascular risk factor for death globally. A large proportion of individuals with high blood pressure (BP) are unaware leading to ...under treatment and poor control. To address this, the International Society of Hypertension (ISH) initiated a global mass screening campaign, the May Measurement Month 2017 (MMM17), in which Kenya participated. Following the success of the campaign, its successor MMM18 was launched. Here, we present the Kenyan results for MMM18. Opportunistic screening of consenting adults was done in various sites across Kenya in May 2018, by volunteers trained using ISH material, under the co-ordination of the Kenya Cardiac Society. Blood pressure, pulse rate, weight, and height were measured by standard methods. Definitions of HTN and statistical methods all adhered to the standard MMM protocol. We screened 49 548 subjects, mean age 39.95 (15.3) years. In total, 49.4% had never had a BP measurement taken. After multiple imputation, 17.1% were hypertensive and of those who were hypertensive, 30.7% were aware, 26.6% were on antihypertensive treatment, and 13.0% had controlled BP. Alcohol use, excess weight, and treatment for HTN were associated with higher BP. The Kenyan MMM18 sites successfully screened more than three times the number screened in 2017, hence improving public awareness. Less than half the population had ever had a BP check. Less than a third of the hypertensives were aware with correspondingly poor treatment and control rates. Opportunistic mass screening is useful in raising public awareness.
Background: The prevalence of ischaemic heart disease and its acute manifestation, acute coronary syndrome (ACS), is growing throughout sub-Saharan Africa, including Kenya. To address this increasing ...problem, we sought to understand the facilitators, context of and barriers to ACS care at Kenyatta National Hospital, with the aim of improving the quality of care of ACS.Methods: We conducted in-depth interviews with healthcare providers involved in the management of ACS patients from January to February 2017 at Kenyatta National Hospital in Nairobi, Kenya. We selected an initial sample of key participants for interviewing and used a snowballing technique to identify additional participants until we achieved saturation. After transcription of audio recordings of the interviews, two authors conducted data coding and analysis using a framework approach.Results: We conducted 16 interviews with healthcare providers. Major themes included the need to improve the diagnostic and therapeutic capabilities of the hospital, including increasing the number of ECG machines and access to thrombolytics. Participants highlighted an overall wide availability of other guideline-directed medical therapies, including antiplatelets, beta-blockers, statins, anticoagulants and ACE inhibitors. All participants also stated the need for and openness to accepting future interventions for improvement of quality of care, including checklists and audits to improve ACS care at Kenyatta National Hospital.Conclusion: Major barriers to ACS care at Kenyatta National Hospital include inadequate diagnostic and therapeutic capabilities, lack of hospital-wide ACS guidelines, undertraining of healthcare providers and delayed presentation of patients seeking care. We also identified potential targets, including checklists and audits for future improvements in quality of care from the perspective of healthcare providers.
Rheumatic heart disease (RHD) accounts for over a million premature deaths annually; however, there is little contemporary information on presentation, complications, and treatment.
This prospective ...registry enrolled 3343 patients (median age 28 years, 66.2% female) presenting with RHD at 25 hospitals in 12 African countries, India, and Yemen between January 2010 and November 2012. The majority (63.9%) had moderate-to-severe multivalvular disease complicated by congestive heart failure (33.4%), pulmonary hypertension (28.8%), atrial fibrillation (AF) (21.8%), stroke (7.1%), infective endocarditis (4%), and major bleeding (2.7%). One-quarter of adults and 5.3% of children had decreased left ventricular (LV) systolic function; 23% of adults and 14.1% of children had dilated LVs. Fifty-five percent (n = 1761) of patients were on secondary antibiotic prophylaxis. Oral anti-coagulants were prescribed in 69.5% (n = 946) of patients with mechanical valves (n = 501), AF (n = 397), and high-risk mitral stenosis in sinus rhythm (n = 48). However, only 28.3% (n = 269) had a therapeutic international normalized ratio. Among 1825 women of childbearing age (12-51 years), only 3.6% (n = 65) were on contraception. The utilization of valvuloplasty and valve surgery was higher in upper-middle compared with lower-income countries.
Rheumatic heart disease patients were young, predominantly female, and had high prevalence of major cardiovascular complications. There is suboptimal utilization of secondary antibiotic prophylaxis, oral anti-coagulation, and contraception, and variations in the use of percutaneous and surgical interventions by country income level.
There are few contemporary data on the mortality and morbidity associated with rheumatic heart disease or information on their predictors. We report the 2-year follow-up of individuals with rheumatic ...heart disease from 14 low- and middle-income countries in Africa and Asia.
Between January 2010 and November 2012, we enrolled 3343 patients from 25 centers in 14 countries and followed them for 2 years to assess mortality, congestive heart failure, stroke or transient ischemic attack, recurrent acute rheumatic fever, and infective endocarditis.
Vital status at 24 months was known for 2960 (88.5%) patients. Two-thirds were female. Although patients were young (median age, 28 years; interquartile range, 18-40), the 2-year case fatality rate was high (500 deaths, 16.9%). Mortality rate was 116.3/1000 patient-years in the first year and 65.4/1000 patient-years in the second year. Median age at death was 28.7 years. Independent predictors of death were severe valve disease (hazard ratio HR, 2.36; 95% confidence interval CI, 1.80-3.11), congestive heart failure (HR, 2.16; 95% CI, 1.70-2.72), New York Heart Association functional class III/IV (HR, 1.67; 95% CI, 1.32-2.10), atrial fibrillation (HR, 1.40; 95% CI, 1.10-1.78), and older age (HR, 1.02; 95% CI, 1.01-1.02 per year increase) at enrollment. Postprimary education (HR, 0.67; 95% CI, 0.54-0.85) and female sex (HR, 0.65; 95% CI, 0.52-0.80) were associated with lower risk of death. Two hundred and four (6.9%) patients had new congestive heart failure (incidence, 38.42/1000 patient-years), 46 (1.6%) had a stroke or transient ischemic attack (8.45/1000 patient-years), 19 (0.6%) had recurrent acute rheumatic fever (3.49/1000 patient-years), and 20 (0.7%) had infective endocarditis (3.65/1000 patient-years). Previous stroke and older age were independent predictors of stroke/transient ischemic attack or systemic embolism. Patients from low- and lower-middle-income countries had significantly higher age- and sex-adjusted mortality than patients from upper-middle-income countries. Valve surgery was significantly more common in upper-middle-income than in lower-middle- or low-income countries.
Patients with clinical rheumatic heart disease have high mortality and morbidity despite being young; those from low- and lower-middle-income countries had a poorer prognosis associated with advanced disease and low education. Programs focused on early detection and the treatment of clinical rheumatic heart disease are required to improve outcomes.