Availability and affordability of cardiovascular disease medicines and their effect on use in high-income, middle-income, and low-income countries: an analysis of the PURE study data

17 million people are estimated to die of cardiovascular diseases worldwide every year.1 About 20% occur in those with known vascular disease.2 Many of these deaths could be avoided if the use3 of proven medicines among patients with vascular disease (secondary prevention) were increased. Clinical guidelines recommend the use of four medicines for the secondary prevention of cardiovascular disease: aspirin, β blockers, angiotensin-converting enzyme (ACE) inhibitors or angiotensin-II receptor blockers (ARBs), and statins.4 However, in a previous report from the Prospective Urban Rural Epidemiology (PURE) study, only 25% of patients with established cardiovascular disease were taking aspirin, 17% β blockers, 20% ACE inhibitors or ARBs, and 15% statins. In high-income countries, 11% of eligible patients were not taking any of these medicines, compared with 80% in low-income countries.

Statistical modelling optimisation of cellulase enzyme immobilisation on functionalised multi-walled carbon nanotubes for empty fruit bunches degradation

Cellulase obtained from the fermentation of sewage treatment plant sludge (STP) by Trichoderma-reesei RUT C-30 was covalently immobilised on functionalised multi-wall carbon nanotubes. Statistical optimisation using the Plackett–Burman design method was implemented to identify parameters with significant effects on the process of immobilisation. The results obtained from this Plackett–Burman design show that three parameters have a significant effect on immobilisation: pH, temperature, and N-ethyl-N-(3-dimethyl aminopropyl) carbodiimide hydrochloride (EDC) concentration. Based on our Plackett-Burman design results, these parameters were further optimised using a face-centred central composite design. The resulting optimum conditions for cellulase immobilisation, as determined by face-centred central composite design, were pH 4.5, 30°C, and 1 mL of 10mg/mL EDC. The amount of immobilised cellulase was approximately 98% using these optimum conditions. The resulting MWCNT-cellulase composite was further characterized by FTIR and SEM. The FTIR spectrum of MWCNT-cellulase composite showed an amide group peak (O = C-NH) corresponding to cellulase enzyme, which confirms that immobilisation took place

Immobilization of cellulases enzyme on Carbon Nanotubes (CNTs) for cellulosic compounds degradation

The fast growing palm oil industry in Malaysia generates, amongst other wastes, Empty Fruit Bunch (EFB) which consists of cellulosic materials. It is one of the major sources of Greenhouse Gases (GHG). However, the bioconversion of cellulosic materials in EFB, a renewable biomass, to valuable products will be the solution to the disposal problem and hence minimize the pollution. The bioconversion of cellulosic materials is carried out by using cellulase enzyme, which itself was extracted from sludge, immobilized on functionalized carbon nanotubes (CNTs) in the presence of coupling reagent. The process parameters such as reaction temperature, reaction time, pH, and amount of enzyme, CNTs dosage and EDC were optimized by using design expert software. The morphology and the structure of CNTs were characterized by Field Emission Scanning Electron Microscopy (FSEM) and Fourier Transform Infrared Absorption Spectroscopic (FTIR). Firstly, carbon nanotubes were functionalized by acidic treatment. Then, the cellulase enzyme is immobilized on the functionalized (CNTs) in a solution of Nhydroxysuccinimide (NHS) and 1-ethyl-3-(3-dimethylamino propyl)-carbodiimide hydrochloride (EDC). The amount of enzyme attached on (CNTs) will be measured through UV spectrometer to determine the cellulases catalytic activity after immobilization and compare it with the free enzyme. Finally, the immobilized enzyme will be tested in the degradation of cellulosic material of empty fruit bunch (EFB) from palm oil mill effluent

Challenges to conducting epidemiology research in chronic conflict areas : examples from PURE- Palestine

Challenges encountered in working within a fragmented health care system include: difficulties in planning for data collection; standardizing data collection when resources are limited; working in communities with access restricted by the military; and other considerations related to the study setting in the occupied Palestinian territory. Data collected from conflict regions may contrast with those solely from politically and economically stable regions. Special efforts to collect epidemiologic data from regions engulfed by strife are essential. This paper describes issues encountered in designing and conducting the Prospective Urban Rural Epidemiology (PURE) study in the occupied Palestinian territory (oPt).Population Health Research Institut

Patient and healthcare provider barriers to hypertension awareness, treatment and follow up: a systematic review and meta-analysis of qualitative and quantitative studies.

BACKGROUND: Although the importance of detecting, treating, and controlling hypertension has been recognized for decades, the majority of patients with hypertension remain uncontrolled. The path from evidence to practice contains many potential barriers, but their role has not been reviewed systematically. This review aimed to synthesize and identify important barriers to hypertension control as reported by patients and healthcare providers. METHODS: Electronic databases MEDLINE, EMBASE and Global Health were searched systematically up to February 2013. Two reviewers independently selected eligible studies. Two reviewers categorized barriers based on a theoretical framework of behavior change. The theoretical framework suggests that a change in behavior requires a strong commitment to change [intention], the necessary skills and abilities to adopt the behavior [capability], and an absence of health system and support constraints. FINDINGS: Twenty-five qualitative studies and 44 quantitative studies met the inclusion criteria. In qualitative studies, health system barriers were most commonly discussed in studies of patients and health care providers. Quantitative studies identified disagreement with clinical recommendations as the most common barrier among health care providers. Quantitative studies of patients yielded different results: lack of knowledge was the most common barrier to hypertension awareness. Stress, anxiety and depression were most commonly reported as barriers that hindered or delayed adoption of a healthier lifestyle. In terms of hypertension treatment adherence, patients mostly reported forgetting to take their medication. Finally, priority setting barriers were most commonly reported by patients in terms of following up with their health care providers. CONCLUSIONS: This review identified a wide range of barriers facing patients and health care providers pursuing hypertension control, indicating the need for targeted multi-faceted interventions. More methodologically rigorous studies that encompass the range of barriers and that include low- and middle-income countries are required in order to inform policies to improve hypertension control

Availability, aff ordability, and consumption of fruits and vegetables in 18 countries across income levels: fi ndings from the Prospective Urban Rural Epidemiology (PURE) study

Background Several international guidelines recommend the consumption of two servings of fruits and three servings of vegetables per day, but their intake is thought to be low worldwide. We aimed to determine the extent to which such low intake is related to availability and aff ordability. Methods We assessed fruit and vegetable consumption using data from country-specifi c, validated semi-quantitative food frequency questionnaires in the Prospective Urban Rural Epidemiology (PURE) study, which enrolled participants from communities in 18 countries between Jan 1, 2003, and Dec 31, 2013. We documented household income data from participants in these communities; we also recorded the diversity and non-sale prices of fruits and vegetables from grocery stores and market places between Jan 1, 2009, and Dec 31, 2013. We determined the cost of fruits and vegetables relative to income per household member. Linear random eff ects models, adjusting for the clustering of households within communities, were used to assess mean fruit and vegetable intake by their relative cost. Findings Of 143 305 participants who reported plausible energy intake in the food frequency questionnaire, mean fruit and vegetable intake was 3·76 servings (95% CI 3·66–3·86) per day. Mean daily consumption was 2·14 servings (1·93–2·36) in low-income countries (LICs), 3·17 servings (2·99–3·35) in lower-middle-income countries (LMICs), 4·31 servings (4·09–4·53) in upper-middle-income countries (UMICs), and 5·42 servings (5·13–5·71) in highincome countries (HICs). In 130 402 participants who had household income data available, the cost of two servings of fruits and three servings of vegetables per day per individual accounted for 51·97% (95% CI 46·06–57·88) of household income in LICs, 18·10% (14·53–21·68) in LMICs, 15·87% (11·51–20·23) in UMICs, and 1·85% (–3·90 to 7·59) in HICs (ptrend=0·0001). In all regions, a higher percentage of income to meet the guidelines was required in rural areas than in urban areas (p<0·0001 for each pairwise comparison). Fruit and vegetable consumption among individuals decreased as the relative cost increased (ptrend=0·00040). Interpretation The consumption of fruit and vegetables is low worldwide, particularly in LICs, and this is associated with low aff ordability. Policies worldwide should enhance the availability and aff ordability of fruits and vegetables

Joint association of urinary sodium and potassium excretion with cardiovascular events and mortality: Prospective cohort study

Objective: To evaluate the joint association of sodium and potassium urinary excretion (as surrogate measures of intake) with cardiovascular events and mortality, in the context of current World Health Organization recommendations for daily intake (\u3c2.0 g sodium, \u3e3.5 g potassium) in adults.Design: International prospective cohort study.Setting: 18 high, middle, and low income countries, sampled from urban and rural communities.Participants: 103 570 people who provided morning fasting urine samples.Main outcome measures: Association of estimated 24 hour urinary sodium and potassium excretion (surrogates for intake) with all cause mortality and major cardiovascular events, using multivariable Cox regression. A six category variable for joint sodium and potassium was generated: sodium excretion (low (\u3c3 g/day), moderate (3-5 g/day), and high (\u3e5 g/day) sodium intakes) by potassium excretion (greater/equal or less than median 2.1 g/day).Results: Mean estimated sodium and potassium urinary excretion were 4.93 g/day and 2.12 g/day, respectively. After a median follow-up of 8.2 years, 7884 (6.1%) participants had died or experienced a major cardiovascular event. Increasing urinary sodium excretion was positively associated with increasing potassium excretion (unadjusted r=0.34), and only 0.002% had a concomitant urinary excretion of \u3c2.0 g/day of sodium and \u3e3.5 g/day of potassium. A J-shaped association was observed of sodium excretion and inverse association of potassium excretion with death and cardiovascular events. For joint sodium and potassium excretion categories, the lowest risk of death and cardiovascular events occurred in the group with moderate sodium excretion (3-5 g/day) and higher potassium excretion (21.9% of cohort). Compared with this reference group, the combinations of low potassium with low sodium excretion (hazard ratio 1.23, 1.11 to 1.37; 7.4% of cohort) and low potassium with high sodium excretion (1.21, 1.11 to 1.32; 13.8% of cohort) were associated with the highest risk, followed by low sodium excretion (1.19, 1.02 to 1.38; 3.3% of cohort) and high sodium excretion (1.10, 1.02 to 1.18; 29.6% of cohort) among those with potassium excretion greater than the median. Higher potassium excretion attenuated the increased cardiovascular risk associated with high sodium excretion (P for interaction=0.007).Conclusions: These findings suggest that the simultaneous target of low sodium intake (\u3c2 g/day) with high potassium intake (\u3e3.5 g/day) is extremely uncommon. Combined moderate sodium intake (3-5 g/day) with high potassium intake is associated with the lowest risk of mortality and cardiovascular events

Potential Deaths Averted and Serious Adverse Events Incurred From Adoption of the SPRINT (Systolic Blood Pressure Intervention Trial) Intensive Blood Pressure Regimen in the United States: Projections From NHANES (National Health and Nutrition Examination Survey)

BACKGROUND: SPRINT (Systolic Blood Pressure Intervention Trial) demonstrated a 27% reduction in all-cause mortality with a systolic blood pressure (SBP) goal ofmellitus, stroke, or heart failure. To quantify the potential benefits and risks of SPRINT intensive goal implementation, we estimated the deaths prevented and excess serious adverse events incurred if the SPRINT intensive SBP treatment goal were implemented in all eligible US adults. METHODS: SPRINT eligibility criteria were applied to the 1999 to 2006 National Health and Nutrition Examination Survey and linked with the National Death Index through December 2011. SPRINT eligibility included age ≥50 years, SBP of 130 to 180 mm Hg (depending on the number of antihypertensive medications being taken), and high cardiovascular disease risk. Exclusion criteria were diabetes mellitus, history of stroke, \u3e1 g proteinuria, heart failure, estimated glomerular filtration ratemL·min RESULTS: The mean age was 68.6 years, and 83.2% and 7.4% were non-Hispanic white and non-Hispanic black, respectively. The annual mortality rate was 2.20% (95% confidence interval [CI], 1.91-2.48), and intensive SBP treatment was projected to prevent ≈107 500 deaths per year (95% CI, 93 300-121 200) and give rise to 56 100 (95% CI, 50 800-61 400) episodes of hypotension, 34 400 (95% CI, 31 200-37 600) episodes of syncope, 43 400 (95% CI, 39 400-47 500) serious electrolyte disorders, and 88 700 (95% CI, 80 400-97 000) cases of acute kidney injury per year. The analysis-of-extremes approach indicated that the range of estimated lower- and upper-bound number of deaths prevented per year with intensive SBP control was 34 600 to 179 600. Intensive SBP control was projected to prevent 46 100 (95% CI, 41 800-50 400) cases of heart failure annually. CONCLUSIONS: If fully implemented in eligible US adults, intensive SBP treatment could prevent ≈107 500 deaths per year. A consequence of this treatment strategy, however, could be an increase in serious adverse events

Availability and affordability of blood pressure-lowering medicines and the effect on blood pressure control in high-income, middle-income, and low-income countries: an analysis of the PURE study data.

BACKGROUND: Hypertension is considered the most important risk factor for cardiovascular diseases, but its control is poor worldwide. We aimed to assess the availability and affordability of blood pressure-lowering medicines, and the association with use of these medicines and blood pressure control in countries at varying levels of economic development. METHODS: We analysed the availability, costs, and affordability of blood pressure-lowering medicines with data recorded from 626 communities in 20 countries participating in the Prospective Urban Rural Epidemiological (PURE) study. Medicines were considered available if they were present in the local pharmacy when surveyed, and affordable if their combined cost was less than 20% of the households' capacity to pay. We related information about availability and affordability to use of these medicines and blood pressure control with multilevel mixed-effects logistic regression models, and compared results for high-income, upper-middle-income, lower-middle-income, and low-income countries. Data for India are presented separately because it has a large generic pharmaceutical industry and a higher availability of medicines than other countries at the same economic level. FINDINGS: The availability of two or more classes of blood pressure-lowering drugs was lower in low-income and middle-income countries (except for India) than in high-income countries. The proportion of communities with four drug classes available was 94% in high-income countries (108 of 115 communities), 76% in India (68 of 90), 71% in upper-middle-income countries (90 of 126), 47% in lower-middle-income countries (107 of 227), and 13% in low-income countries (nine of 68). The proportion of households unable to afford two blood pressure-lowering medicines was 31% in low-income countries (1069 of 3479 households), 9% in middle-income countries (5602 of 65 471), and less than 1% in high-income countries (44 of 10 880). Participants with known hypertension in communities that had all four drug classes available were more likely to use at least one blood pressure-lowering medicine (adjusted odds ratio [OR] 2·23, 95% CI 1·59-3·12); p<0·0001), combination therapy (1·53, 1·13-2·07; p=0·054), and have their blood pressure controlled (2·06, 1·69-2·50; p<0·0001) than were those in communities where blood pressure-lowering medicines were not available. Participants with known hypertension from households able to afford four blood pressure-lowering drug classes were more likely to use at least one blood pressure-lowering medicine (adjusted OR 1·42, 95% CI 1·25-1·62; p<0·0001), combination therapy (1·26, 1·08-1·47; p=0·0038), and have their blood pressure controlled (1·13, 1·00-1·28; p=0·0562) than were those unable to afford the medicines. INTERPRETATION: A large proportion of communities in low-income and middle-income countries do not have access to more than one blood pressure-lowering medicine and, when available, they are often not affordable. These factors are associated with poor blood pressure control. Ensuring access to affordable blood pressure-lowering medicines is essential for control of hypertension in low-income and middle-income countries. FUNDING: Population Health Research Institute, the Canadian Institutes of Health Research, Heart and Stroke Foundation of Ontario, Canadian Institutes of Health Research Strategy for Patient Oriented Research through the Ontario SPOR Support Unit, the Ontario Ministry of Health and Long-Term Care, pharmaceutical companies (with major contributions from AstraZeneca [Canada], Sanofi Aventis [France and Canada], Boehringer Ingelheim [Germany amd Canada], Servier, and GlaxoSmithKline), Novartis and King Pharma, and national or local organisations in participating countries

Cardiovascular risk status of Afro-origin populations across the spectrum of economic development: findings from the Modeling the Epidemiologic Transition Study

Background: Cardiovascular risk factors are increasing in most developing countries. To date, however, very little standardized data has been collected on the primary risk factors across the spectrum of economic development. Data are particularly sparse from Africa. Methods: In the Modeling the Epidemiologic Transition Study (METS) we examined population-based samples of men and women, ages 25–45 of African ancestry in metropolitan Chicago, Kingston, Jamaica, rural Ghana, Cape Town, South Africa, and the Seychelles. Key measures of cardiovascular disease risk are described. Results: The risk factor profile varied widely in both total summary estimates of cardiovascular risk and in the magnitude of component factors. Hypertension ranged from 7% in women from Ghana to 35% in US men. Total cholesterol was well under 200 mg/dl for all groups, with a mean of 155 mg/dl among men in Ghana, South Africa and Jamaica. Among women total cholesterol values varied relatively little by country, following between 160 and 178 mg/dl for all 5 groups. Levels of HDL-C were virtually identical in men and women from all study sites. Obesity ranged from 64% among women in the US to 2% among Ghanaian men, with a roughly corresponding trend in diabetes. Based on the Framingham risk score a clear trend toward higher total risk in association with socioeconomic development was observed among men, while among women there was considerable overlap, with the US participants having only a modestly higher risk score. Conclusions: These data provide a comprehensive estimate of cardiovascular risk across a range of countries at differing stages of social and economic development and demonstrate the heterogeneity in the character and degree of emerging cardiovascular risk. Severe hypercholesterolemia, as characteristic in the US and much of Western Europe at the onset of the coronary epidemic, is unlikely to be a feature of the cardiovascular risk profile in these countries in the foreseeable future, suggesting that stroke may remain the dominant cardiovascular event