Displaying publications 81 - 100 of 226 in total

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  1. Ley B, Luter N, Espino FE, Devine A, Kalnoky M, Lubell Y, et al.
    Malar J, 2015 Sep 29;14:377.
    PMID: 26416229 DOI: 10.1186/s12936-015-0896-8
    The only currently available drug that effectively removes malaria hypnozoites from the human host is primaquine. The use of 8-aminoquinolines is hampered by haemolytic side effects in glucose-6-phosphate dehydrogenase (G6PD) deficient individuals. Recently a number of qualitative and a quantitative rapid diagnostic test (RDT) format have been developed that provide an alternative to the current standard G6PD activity assays. The WHO has recently recommended routine testing of G6PD status prior to primaquine radical cure whenever possible. A workshop was held in the Philippines in early 2015 to discuss key challenges and knowledge gaps that hinder the introduction of routine G6PD testing. Two point-of-care (PoC) test formats for the measurement of G6PD activity are currently available: qualitative tests comparable to malaria RDT as well as biosensors that provide a quantitative reading. Qualitative G6PD PoC tests provide a binomial test result, are easy to use and some products are comparable in price to the widely used fluorescent spot test. Qualitative test results can accurately classify hemizygous males, heterozygous females, but may misclassify females with intermediate G6PD activity. Biosensors provide a more complex quantitative readout and are better suited to identify heterozygous females. While associated with higher costs per sample tested biosensors have the potential for broader use in other scenarios where knowledge of G6PD activity is relevant as well. The introduction of routine G6PD testing is associated with additional costs on top of routine treatment that will vary by setting and will need to be assessed prior to test introduction. Reliable G6PD PoC tests have the potential to play an essential role in future malaria elimination programmes, however require an improved understanding on how to best integrate routine G6PD testing into different health settings.
  2. Cerci JJ, Fanti S, Lobato EE, Kunikowska J, Alonso O, Medina S, et al.
    J Nucl Med, 2022 Feb;63(2):240-247.
    PMID: 34215674 DOI: 10.2967/jnumed.120.261886
    Biochemical recurrence (BCR) is a clinical challenge in prostate cancer (PCa) patients, as recurrence localization guides subsequent therapies. The use of PET with prostate-specific membrane antigen (PSMA) provides better accuracy than conventional imaging practice. This prospective, multicenter, international study was performed to evaluate the diagnostic performance and clinical impact of PSMA PET/CT for evaluating BCR in PCa patients in a worldwide scenario. Methods: Patients were recruited from 17 centers in 15 countries. Inclusion criteria were histopathologically proven prostate adenocarcinoma, previous primary treatment, clinically established BCR, and negative conventional imaging (CT plus bone scintigraphy) and MRI results for patients with PSA levels of 4-10 ng/mL. All patients underwent PET/CT scanning with 68Ga-PSMA-11. Images and data were centrally reviewed. Multivariate logistic regression analysis was applied to identify the independent predictors of PSMA-positive results. Variables were selected for this regression model on the basis of significant associations in the univariate analysis and previous clinical knowledge: Gleason score, the PSA level at the time of the PET scan, PSA doubling time, and primary treatment strategy. All patients were monitored for a minimum of 6 mo. Results: From a total of 1,004 patients, 77.7% were treated initially with radical prostatectomy and 22.3% were treated with radiotherapy. Overall, 65.1% had positive PSMA PET/CT results. PSMA PET/CT positivity was correlated with the Gleason score, PSA level at the time of the PET scan, PSA doubling time, and radiotherapy as the primary treatment (P < 0.001). Treatment was modified on the basis of PSMA PET/CT results in 56.8% of patients. PSMA PET/CT positivity rates were consistent and not statistically different among countries with different incomes. Conclusion: This multicenter, international, prospective trial of PSMA PET/CT confirmed its capability for detecting local and metastatic recurrence in most PCa patients in the setting of BCR. PSMA PET/CT positivity was correlated with the Gleason score, PSA level at the time of the PET scan, PSA doubling time, and radiotherapy as the primary treatment. PSMA PET/CT results led to changes in therapeutic management in more than half of the cohort. The study demonstrated the reliability and worldwide feasibility of PSMA PET/CT in the workup of PCa patients with BCR.
  3. Soon BH, Abu N, Abdul Murad NA, Then SM, Abu Bakar A, Fadzil F, et al.
    Per Med, 2022 01;19(1):25-39.
    PMID: 34873928 DOI: 10.2217/pme-2021-0033
    Aim: Mitochondrial DNA (mtDNA) alterations play an important role in the multistep processes of cancer development. Gliomas are among the most diagnosed brain cancer. The relationship between mtDNA alterations and different grades of gliomas are still elusive. This study aimed to elucidate the profile of somatic mtDNA mutations in different grades of gliomas and correlate it with clinical phenotype. Materials & methods: Forty histopathologically confirmed glioma tissue samples and their matched blood were collected and subjected for mtDNA sequencing. Results & conclusion: About 75% of the gliomas harbored at least one somatic mutation in the mtDNA gene, and 45% of these mutations were pathogenic. Mutations were scattered across the mtDNA genome, and the commonest nonsynonymous mutations were located at complex I and IV of the mitochondrial respiratory chain. These findings may have implication for future research to determine the mitochondrial energetics and its downstream metabolomics on gliomas.
  4. Vishwas S, Kumar R, Khursheed R, Ramanunny AK, Kumar R, Awasthi A, et al.
    Curr Neuropharmacol, 2023;21(7):1558-1574.
    PMID: 35950245 DOI: 10.2174/1570159X20666220810105421
    Quercetin (Qu), a dietary flavonoid, is obtained from many fruits and vegetables such as coriander, broccoli, capers, asparagus, onion, figs, radish leaves, cranberry, walnuts, and citrus fruits. It has proven its role as a nutraceutical owing to numerous pharmacological effects against various diseases in preclinical studies. Despite these facts, Qu and its nanoparticles are less explored in clinical research as a nutraceutical. The present review covers various neuroprotective actions of Qu against various neurodegenerative diseases (NDs) such as Alzheimer's, Parkinson's, Huntington's, and Amyotrophic lateral sclerosis. A literature search was conducted to systematically review the various mechanistic pathways through which Qu elicits its neuroprotective actions and the challenges associated with raw Qu that compromise therapeutic efficacy. The nanoformulations developed to enhance Qu's therapeutic efficacy are also covered. Various ongoing/completed clinical trials related to Qu in treating various diseases, including NDs, are also tabulated. Despite these many successes, the exploration of research on Qu-loaded nanoformulations is limited mostly to preclinical studies, probably due to poor drug loading and stability of the formulation, time-consuming steps involved in the formulation, and their poor scale-up capacity. Hence, future efforts are required in this area to reach Qu nanoformulations to the clinical level.
  5. Awasthi A, Gulati M, Kumar B, Kaur J, Vishwas S, Khursheed R, et al.
    Biomed Res Int, 2022;2022:1659338.
    PMID: 35832856 DOI: 10.1155/2022/1659338
    Diabetic wound (DW) is a secondary application of uncontrolled diabetes and affects about 42.2% of diabetics. If the disease is left untreated/uncontrolled, then it may further lead to amputation of organs. In recent years, huge research has been done in the area of wound dressing to have a better maintenance of DW. These include gauze, films, foams or, hydrocolloid-based dressings as well as polysaccharide- and polymer-based dressings. In recent years, scaffolds have played major role as biomaterial for wound dressing due to its tissue regeneration properties as well as fluid absorption capacity. These are three-dimensional polymeric structures formed from polymers that help in tissue rejuvenation. These offer a large surface area to volume ratio to allow cell adhesion and exudate absorbing capacity and antibacterial properties. They also offer a better retention as well as sustained release of drugs that are directly impregnated to the scaffolds or the ones that are loaded in nanocarriers that are impregnated onto scaffolds. The present review comprehensively describes the pathogenesis of DW, various dressings that are used so far for DW, the limitation of currently used wound dressings, role of scaffolds in topical delivery of drugs, materials used for scaffold fabrication, and application of various polymer-based scaffolds for treating DW.
  6. Savell E, Gilmore AB, Sims M, Mony PK, Koon T, Yusoff K, et al.
    Bull World Health Organ, 2015 Dec 01;93(12):851-61G.
    PMID: 26668437 DOI: 10.2471/BLT.15.155846
    OBJECTIVE: To examine and compare tobacco marketing in 16 countries while the Framework Convention on Tobacco Control requires parties to implement a comprehensive ban on such marketing.

    METHODS: Between 2009 and 2012, a kilometre-long walk was completed by trained investigators in 462 communities across 16 countries to collect data on tobacco marketing. We interviewed community members about their exposure to traditional and non-traditional marketing in the previous six months. To examine differences in marketing between urban and rural communities and between high-, middle- and low-income countries, we used multilevel regression models controlling for potential confounders.

    FINDINGS: Compared with high-income countries, the number of tobacco advertisements observed was 81 times higher in low-income countries (incidence rate ratio, IRR: 80.98; 95% confidence interval, CI: 4.15-1578.42) and the number of tobacco outlets was 2.5 times higher in both low- and lower-middle-income countries (IRR: 2.58; 95% CI: 1.17-5.67 and IRR: 2.52; CI: 1.23-5.17, respectively). Of the 11,842 interviewees, 1184 (10%) reported seeing at least five types of tobacco marketing. Self-reported exposure to at least one type of traditional marketing was 10 times higher in low-income countries than in high-income countries (odds ratio, OR: 9.77; 95% CI: 1.24-76.77). For almost all measures, marketing exposure was significantly lower in the rural communities than in the urban communities.

    CONCLUSION: Despite global legislation to limit tobacco marketing, it appears ubiquitous. The frequency and type of tobacco marketing varies on the national level by income group and by community type, appearing to be greatest in low-income countries and urban communities.

  7. Khatib R, McKee M, Shannon H, Chow C, Rangarajan S, Teo K, et al.
    Lancet, 2016 Jan 2;387(10013):61-9.
    PMID: 26498706 DOI: 10.1016/S0140-6736(15)00469-9
    BACKGROUND: WHO has targeted that medicines to prevent recurrent cardiovascular disease be available in 80% of communities and used by 50% of eligible individuals by 2025. We have previously reported that use of these medicines is very low, but now aim to assess how such low use relates to their lack of availability or poor affordability.
    METHODS: We analysed information about availability and costs of cardiovascular disease medicines (aspirin, β blockers, angiotensin-converting enzyme inhibitors, and statins) in pharmacies gathered from 596 communities in 18 countries participating in the Prospective Urban Rural Epidemiology (PURE) study. Medicines were considered available if present at the pharmacy when surveyed, and affordable if their combined cost was less than 20% of household capacity-to-pay. We compared results from high-income, upper middle-income, lower middle-income, and low-income countries. Data from India were presented separately given its large, generic pharmaceutical industry.
    FINDINGS: Communities were recruited between Jan 1, 2003, and Dec 31, 2013. All four cardiovascular disease medicines were available in 61 (95%) of 64 urban and 27 (90%) of 30 rural communities in high-income countries, 53 (80%) of 66 urban and 43 (73%) of 59 rural communities in upper middle-income countries, 69 (62%) of 111 urban and 42 (37%) of 114 rural communities in lower middle-income countries, eight (25%) of 32 urban and one (3%) of 30 rural communities in low-income countries (excluding India), and 34 (89%) of 38 urban and 42 (81%) of 52 rural communities in India. The four cardiovascular disease medicines were potentially unaffordable for 0·14% of households in high-income countries (14 of 9934 households), 25% of upper middle-income countries (6299 of 24,776), 33% of lower middle-income countries (13,253 of 40,023), 60% of low-income countries (excluding India; 1976 of 3312), and 59% households in India (9939 of 16,874). In low-income and middle-income countries, patients with previous cardiovascular disease were less likely to use all four medicines if fewer than four were available (odds ratio [OR] 0·16, 95% CI 0·04-0·57). In communities in which all four medicines were available, patients were less likely to use medicines if the household potentially could not afford them (0·16, 0·04-0·55).
    INTERPRETATION: Secondary prevention medicines are unavailable and unaffordable for a large proportion of communities and households in upper middle-income, lower middle-income, and low-income countries, which have very low use of these medicines. Improvements to the availability and affordability of key medicines is likely to enhance their use and help towards achieving WHO's targets of 50% use of key medicines by 2025.
    FUNDING: Population Health Research Institute, the Canadian Institutes of Health Research, Heart and Stroke Foundation of Ontario, AstraZeneca (Canada), Sanofi-Aventis (France and Canada), Boehringer Ingelheim (Germany and Canada), Servier, GlaxoSmithKline, Novartis, King Pharma, and national or local organisations in participating countries.
  8. Raina P, Sohel N, Oremus M, Shannon H, Mony P, Kumar R, et al.
    Inj Prev, 2016 Apr;22(2):92-98.
    PMID: 26512093 DOI: 10.1136/injuryprev-2014-041476
    To assess risk factors associated with non-fatal injuries (NFIs) from road traffic accidents (RTAs) or falls.
  9. Dagenais GR, Gerstein HC, Zhang X, McQueen M, Lear S, Lopez-Jaramillo P, et al.
    Diabetes Care, 2016 05;39(5):780-7.
    PMID: 26965719 DOI: 10.2337/dc15-2338
    OBJECTIVE: The goal of this study was to assess whether diabetes prevalence varies by countries at different economic levels and whether this can be explained by known risk factors.

    RESEARCH DESIGN AND METHODS: The prevalence of diabetes, defined as self-reported or fasting glycemia ≥7 mmol/L, was documented in 119,666 adults from three high-income (HIC), seven upper-middle-income (UMIC), four lower-middle-income (LMIC), and four low-income (LIC) countries. Relationships between diabetes and its risk factors within these country groupings were assessed using multivariable analyses.

    RESULTS: Age- and sex-adjusted diabetes prevalences were highest in the poorer countries and lowest in the wealthiest countries (LIC 12.3%, UMIC 11.1%, LMIC 8.7%, and HIC 6.6%; P < 0.0001). In the overall population, diabetes risk was higher with a 5-year increase in age (odds ratio 1.29 [95% CI 1.28-1.31]), male sex (1.19 [1.13-1.25]), urban residency (1.24 [1.11-1.38]), low versus high education level (1.10 [1.02-1.19]), low versus high physical activity (1.28 [1.20-1.38]), family history of diabetes (3.15 [3.00-3.31]), higher waist-to-hip ratio (highest vs. lowest quartile; 3.63 [3.33-3.96]), and BMI (≥35 vs. <25 kg/m(2); 2.76 [2.52-3.03]). The relationship between diabetes prevalence and both BMI and family history of diabetes differed in higher- versus lower-income country groups (P for interaction < 0.0001). After adjustment for all risk factors and ethnicity, diabetes prevalences continued to show a gradient (LIC 14.0%, LMIC 10.1%, UMIC 10.9%, and HIC 5.6%).

    CONCLUSIONS: Conventional risk factors do not fully account for the higher prevalence of diabetes in LIC countries. These findings suggest that other factors are responsible for the higher prevalence of diabetes in LIC countries.

  10. Leong DP, Teo KK, Rangarajan S, Kutty VR, Lanas F, Hui C, et al.
    J Cachexia Sarcopenia Muscle, 2016 12;7(5):535-546.
    PMID: 27104109
    BACKGROUND: The measurement of handgrip strength (HGS) has prognostic value with respect to all-cause mortality, cardiovascular mortality and cardiovascular disease, and is an important part of the evaluation of frailty. Published reference ranges for HGS are mostly derived from Caucasian populations in high-income countries. There is a paucity of information on normative HGS values in non-Caucasian populations from low- or middle-income countries. The objective of this study was to develop reference HGS ranges for healthy adults from a broad range of ethnicities and socioeconomically diverse geographic regions.

    METHODS: HGS was measured using a Jamar dynamometer in 125,462 healthy adults aged 35-70 years from 21 countries in the Prospective Urban Rural Epidemiology (PURE) study.

    RESULTS: HGS values differed among individuals from different geographic regions. HGS values were highest among those from Europe/North America, lowest among those from South Asia, South East Asia and Africa, and intermediate among those from China, South America, and the Middle East. Reference ranges stratified by geographic region, age, and sex are presented. These ranges varied from a median (25th-75th percentile) 50 kg (43-56 kg) in men <40 years from Europe/North America to 18 kg (14-20 kg) in women >60 years from South East Asia. Reference ranges by ethnicity and body-mass index are also reported.

    CONCLUSIONS: Individual HGS measurements should be interpreted using region/ethnic-specific reference ranges.

  11. Duong M, Islam S, Rangarajan S, Leong D, Kurmi O, Teo K, et al.
    Lancet Glob Health, 2019 05;7(5):e613-e623.
    PMID: 31000131 DOI: 10.1016/S2214-109X(19)30070-1
    BACKGROUND: The associations between the extent of forced expiratory volume in 1 s (FEV1) impairment and mortality, incident cardiovascular disease, and respiratory hospitalisations are unclear, and how these associations might vary across populations is unknown.

    METHODS: In this international, community-based cohort study, we prospectively enrolled adults aged 35-70 years who had no intention of moving residences for 4 years from rural and urban communities across 17 countries. A portable spirometer was used to assess FEV1. FEV1 values were standardised within countries for height, age, and sex, and expressed as a percentage of the country-specific predicted FEV1 value (FEV1%). FEV1% was categorised as no impairment (FEV1% ≥0 SD from country-specific mean), mild impairment (FEV1% <0 SD to -1 SD), moderate impairment (FEV1%

  12. Arku RE, Brauer M, Ahmed SH, AlHabib KF, Avezum Á, Bo J, et al.
    Environ Pollut, 2020 Jul;262:114197.
    PMID: 32146361 DOI: 10.1016/j.envpol.2020.114197
    Exposure to air pollution has been linked to elevated blood pressure (BP) and hypertension, but most research has focused on short-term (hours, days, or months) exposures at relatively low concentrations. We examined the associations between long-term (3-year average) concentrations of outdoor PM2.5 and household air pollution (HAP) from cooking with solid fuels with BP and hypertension in the Prospective Urban and Rural Epidemiology (PURE) study. Outdoor PM2.5 exposures were estimated at year of enrollment for 137,809 adults aged 35-70 years from 640 urban and rural communities in 21 countries using satellite and ground-based methods. Primary use of solid fuel for cooking was used as an indicator of HAP exposure, with analyses restricted to rural participants (n = 43,313) in 27 study centers in 10 countries. BP was measured following a standardized procedure and associations with air pollution examined with mixed-effect regression models, after adjustment for a comprehensive set of potential confounding factors. Baseline outdoor PM2.5 exposure ranged from 3 to 97 μg/m3 across study communities and was associated with an increased odds ratio (OR) of 1.04 (95% CI: 1.01, 1.07) for hypertension, per 10 μg/m3 increase in concentration. This association demonstrated non-linearity and was strongest for the fourth (PM2.5 > 62 μg/m3) compared to the first (PM2.5 
  13. Wang C, Bangdiwala SI, Rangarajan S, Lear SA, AlHabib KF, Mohan V, et al.
    Eur Heart J, 2019 05 21;40(20):1620-1629.
    PMID: 30517670 DOI: 10.1093/eurheartj/ehy695
    AIMS: To investigate the association of estimated total daily sleep duration and daytime nap duration with deaths and major cardiovascular events.

    METHODS AND RESULTS: We estimated the durations of total daily sleep and daytime naps based on the amount of time in bed and self-reported napping time and examined the associations between them and the composite outcome of deaths and major cardiovascular events in 116 632 participants from seven regions. After a median follow-up of 7.8 years, we recorded 4381 deaths and 4365 major cardiovascular events. It showed both shorter (≤6 h/day) and longer (>8 h/day) estimated total sleep durations were associated with an increased risk of the composite outcome when adjusted for age and sex. After adjustment for demographic characteristics, lifestyle behaviours and health status, a J-shaped association was observed. Compared with sleeping 6-8 h/day, those who slept ≤6 h/day had a non-significant trend for increased risk of the composite outcome [hazard ratio (HR), 1.09; 95% confidence interval, 0.99-1.20]. As estimated sleep duration increased, we also noticed a significant trend for a greater risk of the composite outcome [HR of 1.05 (0.99-1.12), 1.17 (1.09-1.25), and 1.41 (1.30-1.53) for 8-9 h/day, 9-10 h/day, and >10 h/day, Ptrend < 0.0001, respectively]. The results were similar for each of all-cause mortality and major cardiovascular events. Daytime nap duration was associated with an increased risk of the composite events in those with over 6 h of nocturnal sleep duration, but not in shorter nocturnal sleepers (≤6 h).

    CONCLUSION: Estimated total sleep duration of 6-8 h per day is associated with the lowest risk of deaths and major cardiovascular events. Daytime napping is associated with increased risks of major cardiovascular events and deaths in those with >6 h of nighttime sleep but not in those sleeping ≤6 h/night.

  14. Chow CK, Nguyen TN, Marschner S, Diaz R, Rahman O, Avezum A, et al.
    BMJ Glob Health, 2020 11;5(11).
    PMID: 33148540 DOI: 10.1136/bmjgh-2020-002640
    OBJECTIVES: We aimed to examine the relationship between access to medicine for cardiovascular disease (CVD) and major adverse cardiovascular events (MACEs) among people at high risk of CVD in high-income countries (HICs), upper and lower middle-income countries (UMICs, LMICs) and low-income countries (LICs) participating in the Prospective Urban Rural Epidemiology (PURE) study.

    METHODS: We defined high CVD risk as the presence of any of the following: hypertension, coronary artery disease, stroke, smoker, diabetes or age >55 years. Availability and affordability of blood pressure lowering drugs, antiplatelets and statins were obtained from pharmacies. Participants were categorised: group 1-all three drug types were available and affordable, group 2-all three drugs were available but not affordable and group 3-all three drugs were not available. We used multivariable Cox proportional hazard models with nested clustering at country and community levels, adjusting for comorbidities, sociodemographic and economic factors.

    RESULTS: Of 163 466 participants, there were 93 200 with high CVD risk from 21 countries (mean age 54.7, 49% female). Of these, 44.9% were from group 1, 29.4% from group 2 and 25.7% from group 3. Compared with participants from group 1, the risk of MACEs was higher among participants in group 2 (HR 1.19, 95% CI 1.07 to 1.31), and among participants from group 3 (HR 1.25, 95% CI 1.08 to 1.50).

    CONCLUSION: Lower availability and affordability of essential CVD medicines were associated with higher risk of MACEs and mortality. Improving access to CVD medicines should be a key part of the strategy to lower CVD globally.

  15. Chow CK, Corsi DJ, Gilmore AB, Kruger A, Igumbor E, Chifamba J, et al.
    BMJ Open, 2017 03 31;7(3):e013817.
    PMID: 28363924 DOI: 10.1136/bmjopen-2016-013817
    OBJECTIVES: This study examines in a cross-sectional study 'the tobacco control environment' including tobacco policy implementation and its association with quit ratio.

    SETTING: 545 communities from 17 high-income, upper-middle, low-middle and low-income countries (HIC, UMIC, LMIC, LIC) involved in the Environmental Profile of a Community's Health (EPOCH) study from 2009 to 2014.

    PARTICIPANTS: Community audits and surveys of adults (35-70 years, n=12 953).

    PRIMARY AND SECONDARY OUTCOME MEASURES: Summary scores of tobacco policy implementation (cost and availability of cigarettes, tobacco advertising, antismoking signage), social unacceptability and knowledge were associated with quit ratios (former vs ever smokers) using multilevel logistic regression models.

    RESULTS: Average tobacco control policy score was greater in communities from HIC. Overall 56.1% (306/545) of communities had >2 outlets selling cigarettes and in 28.6% (154/539) there was access to cheap cigarettes (<5cents/cigarette) (3.2% (3/93) in HIC, 0% UMIC, 52.6% (90/171) LMIC and 40.4% (61/151) in LIC). Effective bans (no tobacco advertisements) were in 63.0% (341/541) of communities (81.7% HIC, 52.8% UMIC, 65.1% LMIC and 57.6% LIC). In 70.4% (379/538) of communities, >80% of participants disapproved youth smoking (95.7% HIC, 57.6% UMIC, 76.3% LMIC and 58.9% LIC). The average knowledge score was >80% in 48.4% of communities (94.6% HIC, 53.6% UMIC, 31.8% LMIC and 35.1% LIC). Summary scores of policy implementation, social unacceptability and knowledge were positively and significantly associated with quit ratio and the associations varied by gender, for example, communities in the highest quintile of the combined scores had 5.0 times the quit ratio in men (Odds ratio (OR) 5·0, 95% CI 3.4 to 7.4) and 4.1 times the quit ratio in women (OR 4.1, 95% CI 2.4 to 7.1).

    CONCLUSIONS: This study suggests that more focus is needed on ensuring the tobacco control policy is actually implemented, particularly in LMICs. The gender-related differences in associations of policy, social unacceptability and knowledge suggest that different strategies to promoting quitting may need to be implemented in men compared to women.

  16. Lear SA, Hu W, Rangarajan S, Gasevic D, Leong D, Iqbal R, et al.
    Lancet, 2017 Dec 16;390(10113):2643-2654.
    PMID: 28943267 DOI: 10.1016/S0140-6736(17)31634-3
    BACKGROUND: Physical activity has a protective effect against cardiovascular disease (CVD) in high-income countries, where physical activity is mainly recreational, but it is not known if this is also observed in lower-income countries, where physical activity is mainly non-recreational. We examined whether different amounts and types of physical activity are associated with lower mortality and CVD in countries at different economic levels.

    METHODS: In this prospective cohort study, we recruited participants from 17 countries (Canada, Sweden, United Arab Emirates, Argentina, Brazil, Chile, Poland, Turkey, Malaysia, South Africa, China, Colombia, Iran, Bangladesh, India, Pakistan, and Zimbabwe). Within each country, urban and rural areas in and around selected cities and towns were identified to reflect the geographical diversity. Within these communities, we invited individuals aged between 35 and 70 years who intended to live at their current address for at least another 4 years. Total physical activity was assessed using the International Physical Activity Questionnaire (IPQA). Participants with pre-existing CVD were excluded from the analyses. Mortality and CVD were recorded during a mean of 6·9 years of follow-up. Primary clinical outcomes during follow-up were mortality plus major CVD (CVD mortality, incident myocardial infarction, stroke, or heart failure), either as a composite or separately. The effects of physical activity on mortality and CVD were adjusted for sociodemographic factors and other risk factors taking into account household, community, and country clustering.

    FINDINGS: Between Jan 1, 2003, and Dec 31, 2010, 168 916 participants were enrolled, of whom 141 945 completed the IPAQ. Analyses were limited to the 130 843 participants without pre-existing CVD. Compared with low physical activity (<600 metabolic equivalents [MET] × minutes per week or <150 minutes per week of moderate intensity physical activity), moderate (600-3000 MET × minutes or 150-750 minutes per week) and high physical activity (>3000 MET × minutes or >750 minutes per week) were associated with graded reduction in mortality (hazard ratio 0·80, 95% CI 0·74-0·87 and 0·65, 0·60-0·71; p<0·0001 for trend), and major CVD (0·86, 0·78-0·93; p<0·001 for trend). Higher physical activity was associated with lower risk of CVD and mortality in high-income, middle-income, and low-income countries. The adjusted population attributable fraction for not meeting the physical activity guidelines was 8·0% for mortality and 4·6% for major CVD, and for not meeting high physical activity was 13·0% for mortality and 9·5% for major CVD. Both recreational and non-recreational physical activity were associated with benefits.

    INTERPRETATION: Higher recreational and non-recreational physical activity was associated with a lower risk of mortality and CVD events in individuals from low-income, middle-income, and high-income countries. Increasing physical activity is a simple, widely applicable, low cost global strategy that could reduce deaths and CVD in middle age.

    FUNDING: Population Health Research Institute, the Canadian Institutes of Health Research, Heart and Stroke Foundation of Ontario, Ontario SPOR Support Unit, Ontario Ministry of Health and Long-Term Care, AstraZeneca, Sanofi-Aventis, Boehringer Ingelheim, Servier, GSK, Novartis, King Pharma, and national and local organisations in participating countries that are listed at the end of the Article.
  17. Mente A, Dehghan M, Rangarajan S, McQueen M, Dagenais G, Wielgosz A, et al.
    Lancet Diabetes Endocrinol, 2017 10;5(10):774-787.
    PMID: 28864143 DOI: 10.1016/S2213-8587(17)30283-8
    BACKGROUND: The relation between dietary nutrients and cardiovascular disease risk markers in many regions worldwide is unknown. In this study, we investigated the effect of dietary nutrients on blood lipids and blood pressure, two of the most important risk factors for cardiovascular disease, in low-income, middle-income, and high-income countries.

    METHODS: We studied 125 287 participants from 18 countries in North America, South America, Europe, Africa, and Asia in the Prospective Urban Rural Epidemiology (PURE) study. Habitual food intake was measured with validated food frequency questionnaires. We assessed the associations between nutrients (total fats, saturated fatty acids, monounsaturated fatty acids, polyunsaturated fatty acids, carbohydrates, protein, and dietary cholesterol) and cardiovascular disease risk markers using multilevel modelling. The effect of isocaloric replacement of saturated fatty acids with other fats and carbohydrates was determined overall and by levels of intakes by use of nutrient density models. We did simulation modelling in which we assumed that the effects of saturated fatty acids on cardiovascular disease events was solely related to their association through an individual risk marker, and then compared these simulated risk marker-based estimates with directly observed associations of saturated fatty acids with cardiovascular disease events.

    FINDINGS: Participants were enrolled into the study from Jan 1, 2003, to March 31, 2013. Intake of total fat and each type of fat was associated with higher concentrations of total cholesterol and LDL cholesterol, but also with higher HDL cholesterol and apolipoprotein A1 (ApoA1), and lower triglycerides, ratio of total cholesterol to HDL cholesterol, ratio of triglycerides to HDL cholesterol, and ratio of apolipoprotein B (ApoB) to ApoA1 (all ptrend<0·0001). Higher carbohydrate intake was associated with lower total cholesterol, LDL cholesterol, and ApoB, but also with lower HDL cholesterol and ApoA1, and higher triglycerides, ratio of total cholesterol to HDL cholesterol, ratio of triglycerides to HDL cholesterol, and ApoB-to-ApoA1 ratio (all ptrend<0·0001, apart from ApoB [ptrend=0·0014]). Higher intakes of total fat, saturated fatty acids, and carbohydrates were associated with higher blood pressure, whereas higher protein intake was associated with lower blood pressure. Replacement of saturated fatty acids with carbohydrates was associated with the most adverse effects on lipids, whereas replacement of saturated fatty acids with unsaturated fats improved some risk markers (LDL cholesterol and blood pressure), but seemed to worsen others (HDL cholesterol and triglycerides). The observed associations between saturated fatty acids and cardiovascular disease events were approximated by the simulated associations mediated through the effects on the ApoB-to-ApoA1 ratio, but not with other lipid markers including LDL cholesterol.

    INTERPRETATION: Our data are at odds with current recommendations to reduce total fat and saturated fats. Reducing saturated fatty acid intake and replacing it with carbohydrate has an adverse effect on blood lipids. Substituting saturated fatty acids with unsaturated fats might improve some risk markers, but might worsen others. Simulations suggest that ApoB-to-ApoA1 ratio probably provides the best overall indication of the effect of saturated fatty acids on cardiovascular disease risk among the markers tested. Focusing on a single lipid marker such as LDL cholesterol alone does not capture the net clinical effects of nutrients on cardiovascular risk.

    FUNDING: Full funding sources listed at the end of the paper (see Acknowledgments).

  18. Joseph P, Yusuf S, Lee SF, Ibrahim Q, Teo K, Rangarajan S, et al.
    Heart, 2018 04;104(7):581-587.
    PMID: 29066611 DOI: 10.1136/heartjnl-2017-311609
    OBJECTIVE: To evaluate the performance of the non-laboratory INTERHEART risk score (NL-IHRS) to predict incident cardiovascular disease (CVD) across seven major geographic regions of the world. The secondary objective was to evaluate the performance of the fasting cholesterol-based IHRS (FC-IHRS).

    METHODS: Using measures of discrimination and calibration, we tested the performance of the NL-IHRS (n=100 475) and FC-IHRS (n=107 863) for predicting incident CVD in a community-based, prospective study across seven geographic regions: South Asia, China, Southeast Asia, Middle East, Europe/North America, South America and Africa. CVD was defined as the composite of cardiovascular death, myocardial infarction, stroke, heart failure or coronary revascularisation.

    RESULTS: Mean age of the study population was 50.53 (SD 9.79) years and mean follow-up was 4.89 (SD 2.24) years. The NL-IHRS had moderate to good discrimination for incident CVD across geographic regions (concordance statistic (C-statistic) ranging from 0.64 to 0.74), although recalibration was necessary in all regions, which improved its performance in the overall cohort (increase in C-statistic from 0.69 to 0.72, p<0.001). Regional recalibration was also necessary for the FC-IHRS, which also improved its overall discrimination (increase in C-statistic from 0.71 to 0.74, p<0.001). In 85 078 participants with complete data for both scores, discrimination was only modestly better with the FC-IHRS compared with the NL-IHRS (0.74 vs 0.73, p<0.001).

    CONCLUSIONS: External validations of the NL-IHRS and FC-IHRS suggest that regionally recalibrated versions of both can be useful for estimating CVD risk across a diverse range of community-based populations. CVD prediction using a non-laboratory score can provide similar accuracy to laboratory-based methods.

  19. Duong M, Rangarajan S, Zaman M, Nasir NM, Seron P, Yeates K, et al.
    PLOS Glob Public Health, 2022;2(2):e0000141.
    PMID: 36962310 DOI: 10.1371/journal.pgph.0000141
    INTRODUCTION: Portable spirometers are commonly used in longitudinal epidemiological studies to measure and track the forced expiratory volume in first second (FEV1) and forced vital capacity (FVC). During the course of the study, it may be necessary to replace spirometers with a different model. This raise questions regarding the comparability of measurements from different devices. We examined the correlation, mean differences and agreement between two different spirometers, across diverse populations and different participant characteristics.

    METHODS: From June 2015 to Jan 2018, a total of 4,603 adults were enrolled from 628 communities in 18 countries and 7 regions of the world. Each participant performed concurrent measurements from the MicroGP and EasyOne spirometer. Measurements were compared by the intra-class correlation coefficient (ICC) and Bland-Altman method.

    RESULTS: Approximately 65% of the participants achieved clinically acceptable quality measurements. Overall correlations between paired FEV1 (ICC 0.88 [95% CI 0.87, 0.88]) and FVC (ICC 0.84 [0.83, 0.85]) were high. Mean differences between paired FEV1 (-0.038 L [-0.053, -0.023]) and FVC (0.033 L [0.012, 0.054]) were small. The 95% limits of agreement were wide but unbiased (FEV1 984, -1060; FVC 1460, -1394). Similar findings were observed across regions. The source of variation between spirometers was mainly at the participant level. Older age, higher body mass index, tobacco smoking and known COPD/asthma did not adversely impact on the inter-device variability. Furthermore, there were small and acceptable mean differences between paired FEV1 and FVC z-scores using the Global Lung Initiative normative values, suggesting minimal impact on lung function interpretation.

    CONCLUSIONS: In this multicenter, diverse community-based cohort study, measurements from two portable spirometers provided good correlation, small and unbiased differences between measurements. These data support their interchangeable use across diverse populations to provide accurate trends in serial lung function measurements in epidemiological studies.

  20. Iqbal R, Dehghan M, Mente A, Rangarajan S, Wielgosz A, Avezum A, et al.
    Am J Clin Nutr, 2021 09 01;114(3):1049-1058.
    PMID: 33787869 DOI: 10.1093/ajcn/nqaa448
    BACKGROUND: Dietary guidelines recommend limiting red meat intake because it is a major source of medium- and long-chain SFAs and is presumed to increase the risk of cardiovascular disease (CVD). Evidence of an association between unprocessed red meat intake and CVD is inconsistent.

    OBJECTIVE: The study aimed to assess the association of unprocessed red meat, poultry, and processed meat intake with mortality and major CVD.

    METHODS: The Prospective Urban Rural Epidemiology (PURE) Study is a cohort of 134,297 individuals enrolled from 21 low-, middle-, and high-income countries. Food intake was recorded using country-specific validated FFQs. The primary outcomes were total mortality and major CVD. HRs were estimated using multivariable Cox frailty models with random intercepts.

    RESULTS: In the PURE study, during 9.5 y of follow-up, we recorded 7789 deaths and 6976 CVD events. Higher unprocessed red meat intake (≥250 g/wk vs. <50 g/wk) was not significantly associated with total mortality (HR: 0.93; 95% CI: 0.85, 1.02; P-trend = 0.14) or major CVD (HR: 1.01; 95% CI: 0.92, 1.11; P-trend = 0.72). Similarly, no association was observed between poultry intake and health outcomes. Higher intake of processed meat (≥150 g/wk vs. 0 g/wk) was associated with higher risk of total mortality (HR: 1.51; 95% CI: 1.08, 2.10; P-trend = 0.009) and major CVD (HR: 1.46; 95% CI: 1.08, 1.98; P-trend = 0.004).

    CONCLUSIONS: In a large multinational prospective study, we did not find significant associations between unprocessed red meat and poultry intake and mortality or major CVD. Conversely, a higher intake of processed meat was associated with a higher risk of mortality and major CVD.

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