Variations in common diseases, hospital admissions, and deaths in middle-aged adults in 21 countries from five continents (PURE): a prospective cohort study

BACKGROUND: To our knowledge, no previous study has prospectively documented the incidence of common diseases and related mortality in high-income countries (HICs), middle-income countries (MICs), and low-income countries (LICs) with standardised approaches. Such information is key to developing global and context-specific health strategies. In our analysis of the Prospective Urban Rural Epidemiology (PURE) study, we aimed to evaluate differences in the incidence of common diseases, related hospital admissions, and related mortality in a large contemporary cohort of adults from 21 HICs, MICs, and LICs across five continents by use of standardised approaches. METHODS: The PURE study is a prospective, population-based cohort study of individuals aged 35-70 years who have been enrolled from 21 countries across five continents. The key outcomes were the incidence of fatal and non-fatal cardiovascular diseases, cancers, injuries, respiratory diseases, and hospital admissions, and we calculated the age-standardised and sex-standardised incidence of these events per 1000 person-years. FINDINGS: This analysis assesses the incidence of events in 162 534 participants who were enrolled in the first two phases of the PURE core study, between Jan 6, 2005, and Dec 4, 2016, and who were assessed for a median of 9·5 years (IQR 8·5-10·9). During follow-up, 11 307 (7·0%) participants died, 9329 (5·7%) participants had cardiovascular disease, 5151 (3·2%) participants had a cancer, 4386 (2·7%) participants had injuries requiring hospital admission, 2911 (1·8%) participants had pneumonia, and 1830 (1·1%) participants had chronic obstructive pulmonary disease (COPD). Cardiovascular disease occurred more often in LICs (7·1 cases per 1000 person-years) and in MICs (6·8 cases per 1000 person-years) than in HICs (4·3 cases per 1000 person-years). However, incident cancers, injuries, COPD, and pneumonia were most common in HICs and least common in LICs. Overall mortality rates in LICs (13·3 deaths per 1000 person-years) were double those in MICs (6·9 deaths per 1000 person-years) and four times higher than in HICs (3·4 deaths per 1000 person-years). This pattern of the highest mortality in LICs and the lowest in HICs was observed for all causes of death except cancer, where mortality was similar across country income levels. Cardiovascular disease was the most common cause of deaths overall (40%) but accounted for only 23% of deaths in HICs (vs 41% in MICs and 43% in LICs), despite more cardiovascular disease risk factors (as judged by INTERHEART risk scores) in HICs and the fewest such risk factors in LICs. The ratio of deaths from cardiovascular disease to those from cancer was 0·4 in HICs, 1·3 in MICs, and 3·0 in LICs, and four upper-MICs (Argentina, Chile, Turkey, and Poland) showed ratios similar to the HICs. Rates of first hospital admission and cardiovascular disease medication use were lowest in LICs and highest in HICs. INTERPRETATION: Among adults aged 35-70 years, cardiovascular disease is the major cause of mortality globally. However, in HICs and some upper-MICs, deaths from cancer are now more common than those from cardiovascular disease, indicating a transition in the predominant causes of deaths in middle-age. As cardiovascular disease decreases in many countries, mortality from cancer will probably become the leading cause of death. The high mortality in poorer countries is not related to risk factors, but it might be related to poorer access to health care. (AU)

Education and risk for acute myocardial infarction in 52 high, middle and low-income countries: INTERHEART case-control study

Objective: To determine the effect of education and other measures of socioeconomic status (SES) on risk ofacute myocardial infarction (AMI) in patients and controls from countries with diverse economic circumstances(high, middle, and low income countries). Design: Case-control study.Setting: 52 countries from all inhabited regions of the world.Participants: 12242 cases and 14622 controls. Main outcome measures: First non-fatal AMI. Results: SES was measured using education, familyincome, possessions in the household and occupation. Low levels of education ((8 years) were more commonin cases compared to controls (45.0% and 38.1%; p,0.0001). The odds ratio (OR) for low education adjusted for age, sex and region was 1.56 (95% confidence interval 1.47 to 1.66). After further adjustment for psychosocial, lifestyle, other factors and mutually forother socioeconomic factors, the OR associated with education (8 years was 1.31 (1.20 to 1.44) (p,0.0001). Modifiable lifestyle factors (smoking, exercise, consumption of vegetables and fruits, alcohol and abdominal obesity) explained about half of the socioeconomic gradient. Family income, numbers of possessions and non-professional occupation were only weakly or not at all independently related to AMI. In high-income countries (World Bank Classification), the risk factor adjusted OR associated with low education was 1.61 (1.33 to 1.94), whereas it was substantially lower in lowincome and middle-income countries: 1.25 (1.14 to 1.37) (p for interaction 0.045). Conclusion: Of the SES measures we studied, low education was the marker most consistently associated with increased risk for AMI globally, most markedly in high-income countries.

Education and risk for acute myocardial infarction in 52 high, middle and low-income countries: INTERHEART case-control study.

OBJECTIVE: To determine the effect of education and other measures of socioeconomic status (SES) on risk of acute myocardial infarction (AMI) in patients and controls from countries with diverse economic circumstances (high, middle, and low income countries). DESIGN: Case-control study. SETTING: 52 countries from all inhabited regions of the world. PARTICIPANTS: 12242 cases and 14622 controls. MAIN OUTCOME MEASURES: First non-fatal AMI. RESULTS: SES was measured using education, family income, possessions in the household and occupation. Low levels of education (< or =8 years) were more common in cases compared to controls (45.0% and 38.1%; p<0.0001). The odds ratio (OR) for low education adjusted for age, sex and region was 1.56 (95% confidence interval 1.47 to 1.66). After further adjustment for psychosocial, lifestyle, other factors and mutually for other socioeconomic factors, the OR associated with education < or =8 years was 1.31 (1.20 to 1.44) (p<0.0001). Modifiable lifestyle factors (smoking, exercise, consumption of vegetables and fruits, alcohol and abdominal obesity) explained about half of the socioeconomic gradient. Family income, numbers of possessions and non-professional occupation were only weakly or not at all independently related to AMI. In high-income countries (World Bank Classification), the risk factor adjusted OR associated with low education was 1.61 (1.33 to 1.94), whereas it was substantially lower in low-income and middle-income countries: 1.25 (1.14 to 1.37) (p for interaction 0.045). CONCLUSION: Of the SES measures we studied, low education was the marker most consistently associated with increased risk for AMI globally, most markedly in high-income countries.

Effectiveness of research training workshop taught by traditional and video-teleconference methods in a developing country.

The developing countries are currently facing a double burden of communicable and non-communicable diseases. Physician-scientists, trained in patient care and research skills are crucial in performing cutting-edge clinical research in the developing countries. A major unmet challenge has been the lack of local expertise and the increasing problem of 'brain drain'. The current study was an effort to present and assess a model of research training to health-care professionals in Pakistan in order to increase the research skills. The objective of the current study was to assess the effectiveness of two different methods of research training. An epidemiologic research training workshop was offered to health-care professionals in Pakistan by face-to-face (F2F) and video-teleconferencing (VTC) methods. A total of 38 F2F and 18 VTC participants were included in the workshop which was conducted by research faculty from the University of Pittsburgh. To assess knowledge, pre- and post-test were done. Within each group, paired sample T-test showed significant improvement in scores after the completion of workshop (p<0.001 for F2F and VTC). In the F2F group, mean scores increased from 11.13 (pre-test) to 15.08 (post-test) and in the VTC group, scores increased from 10.67 (pre-test) to 13.22 (post-test). Two sample T-test was found statistically significant (p<0.001). We present a model for training physicians in public health by providing in-house research skills training which can be used to strengthen the local capacity and reduce increasing problems of brain drain.

Measuring elevated microvascular permeability and predicting hemorrhagic transformation in acute ischemic stroke using first-pass dynamic perfusion CT imaging.

BACKGROUND AND PURPOSE: Hemorrhagic transformation (HT) can be a devastating complication of acute ischemic stroke (AIS). The purpose of this study was to determine whether increased microvascular permeability (PS) of the blood-brain barrier was detected in early AIS by using first-pass dynamic perfusion CT (PCT) and whether PS was significantly higher in infarcts destined for HT. MATERIALS AND METHODS: Fifty patients with AIS less than 3 hours old and evaluated by PCT were included. PS color maps were retrospectively generated from PCT data using the Patlak model. One reader analyzed each PS map by drawing 4 circular 10-mm regions of interest on any focal abnormality. The mean of these 4 regions of interest represented the PS of the infarct (PSinfarct). The mean of 4 mirror regions of interest on the nonischemic contralateral hemisphere was also obtained (PScontrol). PSinfarct and PScontrol were compared by using an exact Wilcoxon test. PSinfarct for infarcts that developed HT on follow-up (PSHT) was compared with all of the others (PSNo-HT) using an exact Mann-Whitney test. RESULTS: Forty-four infarcts (88%) showed focal PS elevation in the region of infarct. In units of milliliters per 100 milliliters per minute, PSinfarct ranged from 0 to 13 (mean: 3.5+/-3.1) versus PScontrol of 0-0.8 (mean: 0.28+/-0.27; P<.0001). Six infarcts (12%) developed HT, all of which were within the region of PS elevation. PSHT ranged from 5.2 to 13 (mean: 9.8+/-2.9) versus PSNo-HT of 0-5.9 (mean: 2.7+/-2.0; P<.0001). Eighteen infarcts (36%) were treated with recombinant tissue plasminogen activator (rtPA). A significant difference between PSHT and PSNo-HT persisted irrespective of rtPA treatment. CONCLUSIONS: Elevated permeability was detectable in AIS by using first-pass PCT and it predicted subsequent HT.

Role of vitamins B6, B12 and folic acid on hyperhomocysteinemia in a Pakistani population of patients with acute myocardial infarction.

BACKGROUND AND AIM: Pakistani people belong to an ethnic group which has the highest rate of coronary artery disease (CAD). We investigated the possible correlation between deficiency of vitamins B6, B12 or folic acid and hyperhomocysteinemia in Pakistani patients with acute myocardial infarction (AMI). A case-control study was carried out involving 224 AMI patients (age 30-70 years; 55 females and 169 males) and 126 normal healthy subjects (age 31-70 years; 35 females and 91 males). METHODS AND RESULTS: Fasting venous blood was obtained from cases and controls. Serum was analyzed for folic acid and B12 using radioassays. Plasma was analyzed for pyridoxal phosphate (PLP; coenzymic form of B6) using a radioenzymatic assay and for total homocysteine using a fluorescence polarization immunoassay. Mean serum B12 concentration in AMI patients was found to be significantly lower than the mean for controls (241+/-185 pg/ml vs 608+/-341 pg/ml; p < 0.001). Mean serum folate level in patients was also found to be lower than controls (3.35+/-3.78 ng/ml vs 4.93+/-2.93 ng/ml), however, the differences were not statistically significant. Similarly, mean PLP concentration in plasma of cases (19.4+/-24.4 nmol/l) was lower than the concentration in controls (23.2+/-17.6 nmol/l), but the difference was not statistically significant. Mean plasma homocysteine level in AMI cases (18+/-8.36 micromol/l) was higher than the mean level in controls (16.4+/-4.9 micromol/l), but not to a significant extent. However, this mean homocysteine concentration in normal healthy subjects was among the highest reported in the literature and was significantly more than mean values reported in most Eastern and Western studies. Compared to controls, there was significantly greater deficiency of folate (32.5% vs 67.1%), B12 (3.2% vs 63.4%) and PLP (49.2% vs 74.1%) in AMI patients. Deficiencies of folate, B12 and PLP were defined as serum folate levels less than 3.5 ng/ml, serum levels of B12 less than 200 pg/ml and plasma PLP levels less than 20 nmol/l. Mean plasma homocysteine levels in smokers were found to be significantly higher in both cases and controls. Similarly, mean serum folate levels in smokers (compared to nonsmokers) were significantly lower in both cases and controls. CONCLUSIONS: Substantial nutritional deficiencies of these three vitamins along with mild hyperhomocysteinemia, perhaps through an interplay with the classical cardiovascular risk factors (highly prevalent in this population), could be further aggravating the risk of CAD in the Pakistani population.

Closure of aortopulmonary window with amplatzer duct occluder device.

Aortopulmonary window is a relatively uncommon congenital heart defect. We report on a patient with a small aortopulmonary window, who presented with an asymptomatic murmur and in whom catheter closure was successfully performed with an Amplatzer Duct Occluder.

Sickle cell anaemia in Pakistan.

The sickle cell gene is found predominantly in Equatorial Africa and amongst the negro population in the United States. It has also been reported in Saudi Arabia, the Middle East, Southern India and Iran. Despite human migration from the Middle East, Iran and India to Pakistan, there have to date been no reported cases of sickle cell disease in Pakistan to the best of our knowledge. But unfortunately there has been no population screening to find out the true incidence of the disease. Our study demonstrates that the disease is not totally non-existent in Pakistan: over a two-year period we have collected eight cases in our department. Electrophoretic screening is obviously needed to find out the true incidence of the disease/trait.

Transverse myelitis and hepatitis in varicella.

We describe a case with several grave complications of varicella rarely encountered in previously healthy young individuals.

Primary hepatic actinomycosis: a diagnostic problem.

A fatal case of hepatic actinomycosis in an immuno-compromised host is described. Diagnosis was delayed because of the rarity of this disease and because amoebic liver abscess, common in the tropics, has a similar presentation.