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1.  Dietary patterns in India and their association with obesity and central obesity 
Public health nutrition  2015;18(16):3031-3041.
Objective
Obesity is a growing problem in India, dietary determinants of which have been studied using an ‘individual food/nutrient’ approach. Examining dietary patterns may provide more coherent findings, but few studies in developing countries have adopted this approach. This study aimed to identify dietary patterns in an Indian population and assess their relationship with anthropometric risk factors.
Design
Food Frequency Questionnaire data from the cross-sectional sib-pair Indian Migration Study (IMS) (n=7067), was used to identify dietary patterns using principal component analysis. Mixed-effects logistic regression was used to examine associations with obesity and central obesity.
Setting
IMS was conducted at four factory locations across India: Lucknow, Nagpur, Hyderabad, Bangalore.
Subjects
The participants were rural-to-urban migrant and urban non-migrant factory workers, their rural and urban resident siblings, and their co-resident spouses.
Results
Three dietary patterns were identified, ‘cereals-savoury foods’ (cooked grains, rice/rice-based dishes, snacks, condiments, soups, nuts), ‘fruit-veg-sweets-snacks’ (western cereals, vegetables, fruit, fruit juices, cooked milk products, snacks, sugars, sweets), and ‘animal-food’ (red meat, poultry, fish/seafood, eggs). In adjusted analysis, positive graded associations were found between the ‘animal-food’ pattern and both anthropometric risk factors. Moderate intake of the ‘cereals-savoury foods’ pattern was associated with reduced odds of obesity and central obesity.
Conclusion
Distinct dietary patterns were identified in a large Indian sample, which were different from those identified in previous literature. A clear ‘plant-based/animal food-based pattern’ dichotomy emerged, with the latter being associated with higher odds of anthropometric risk factors. Longitudinal studies are needed to further clarify this relationship in India.
doi:10.1017/S1368980015000312
PMCID: PMC4831640  PMID: 25697609
2.  Migration and DNA methylation: a comparison of methylation patterns in type 2 diabetes susceptibility genes between indians and europeans 
Background
Type 2 diabetes is a global problem that is increasingly prevalent in low and middle income countries including India, and is partly attributed to increased urbanisation. Genotype clearly plays a role in type 2 diabetes susceptibility. However, the role of DNA methylation and its interaction with genotype and metabolic measures is poorly understood. This study aimed to establish whether methylation patterns of type 2 diabetes genes differ between distinct Indian and European populations and/or change following rural to urban migration in India.
Methods
Quantitative DNA methylation analysis in Indians and Europeans using Sequenom® EpiTYPER® technology was undertaken in three genes: ADCY5, FTO and KCNJ11. Metabolic measures and genotype data were also analysed.
Results
Consistent differences in DNA methylation patterns were observed between Indian and European populations in ADCY5, FTO and KCNJ11. Associations were demonstrated between FTO rs9939609 and BMI and between ADCY5rs17295401 and HDL levels in Europeans. However, these observations were not linked to local variation in DNA methylation levels. No differences in methylation patterns were observed in urban-dwelling migrants compared to their non-migrant rural-dwelling siblings in India.
Conclusions
Analysis of DNA methylation at three type 2 diabetes susceptibility loci highlighted geographical and ethnic differences in methylation patterns. These differences may be attributed to genetic and/or region-specific environmental factors.
doi:10.7243/2050-0866-2-6
PMCID: PMC4835020  PMID: 27099715
Type 2 diabetes; DNA methylation; ethnicity
3.  Quantifying the impact of rising food prices on child mortality in India: a cross-district statistical analysis of the District Level Household Survey 
Background: Rates of child malnutrition and mortality in India remain high. We tested the hypothesis that rising food prices are contributing to India’s slow progress in improving childhood survival.
Methods: Using rounds 2 and 3 (2002—08) of the Indian District Level Household Survey, we calculated neonatal, infant and under-five mortality rates in 364 districts, and merged these with district-level food price data from the National Sample Survey Office. Multivariate models were estimated, stratified into 27 less deprived states and territories and 8 deprived states (‘Empowered Action Groups’).
Results: Between 2002 and 2008, the real price of food in India rose by 11.7%. A 1% increase in total food prices was associated with a 0.49% increase in neonatal (95% confidence interval (CI): 0.13% to 0.85%), but not infant or under-five mortality rates. Disaggregating by type of food and level of deprivation, in the eight deprived states, we found an elevation in neonatal mortality rates of 0.33% for each 1% increase in the price of meat (95% CI: 0.06% to 0.60%) and 0.10% for a 1% increase in dairy (95% CI: 0.01% to 0.20%). We also detected an adverse association of the price of dairy with infant (b = 0.09%; 95% CI: 0.01% to 0.16%) and under-five mortality rates (b = 0.10%; 95% CI: 0.03% to 0.17%). These associations were not detected in less deprived states and territories.
Conclusions: Rising food prices, particularly of high-protein meat and dairy products, were associated with worse child mortality outcomes. These adverse associations were concentrated in the most deprived states.
doi:10.1093/ije/dyv359
PMCID: PMC4864878  PMID: 27063607
food prices; mortality; child health; India
4.  Plasma urate concentration and risk of coronary heart disease: a Mendelian randomisation analysis 
Summary
Background
Increased circulating plasma urate concentration is associated with an increased risk of coronary heart disease, but the extent of any causative effect of urate on risk of coronary heart disease is still unclear. In this study, we aimed to clarify any causal role of urate on coronary heart disease risk using Mendelian randomisation analysis.
Methods
We first did a fixed-effects meta-analysis of the observational association of plasma urate and risk of coronary heart disease. We then used a conventional Mendelian randomisation approach to investigate the causal relevance using a genetic instrument based on 31 urate-associated single nucleotide polymorphisms (SNPs). To account for potential pleiotropic associations of certain SNPs with risk factors other than urate, we additionally did both a multivariable Mendelian randomisation analysis, in which the genetic associations of SNPs with systolic and diastolic blood pressure, HDL cholesterol, and triglycerides were included as covariates, and an Egger Mendelian randomisation (MR-Egger) analysis to estimate a causal effect accounting for unmeasured pleiotropy.
Findings
In the meta-analysis of 17 prospective observational studies (166 486 individuals; 9784 coronary heart disease events) a 1 SD higher urate concentration was associated with an odds ratio (OR) for coronary heart disease of 1·07 (95% CI 1·04–1·10). The corresponding OR estimates from the conventional, multivariable adjusted, and Egger Mendelian randomisation analysis (58 studies; 198 598 individuals; 65 877 events) were 1·18 (95% CI 1·08–1·29), 1·10 (1·00–1·22), and 1·05 (0·92–1·20), respectively, per 1 SD increment in plasma urate.
Interpretation
Conventional and multivariate Mendelian randomisation analysis implicates a causal role for urate in the development of coronary heart disease, but these estimates might be inflated by hidden pleiotropy. Egger Mendelian randomisation analysis, which accounts for pleiotropy but has less statistical power, suggests there might be no causal effect. These results might help investigators to determine the priority of trials of urate lowering for the prevention of coronary heart disease compared with other potential interventions.
Funding
UK National Institute for Health Research, British Heart Foundation, and UK Medical Research Council.
doi:10.1016/S2213-8587(15)00386-1
PMCID: PMC4805857  PMID: 26781229
5.  Lipids, obesity and gallbladder disease in women: insights from genetic studies using the cardiovascular gene-centric 50K SNP array 
Gallbladder disease (GBD) has an overall prevalence of 10–40% depending on factors such as age, gender, population, obesity and diabetes, and represents a major economic burden. Although gallstones are composed of cholesterol by-products and are associated with obesity, presumed causal pathways remain unproven, although BMI reduction is typically recommended. We performed genetic studies to discover candidate genes and define pathways involved in GBD. We genotyped 15 241 women of European ancestry from three cohorts, including 3216 with GBD, using the Human cardiovascular disease (HumanCVD) BeadChip containing up to ~53 000 single-nucleotide polymorphisms (SNPs). Effect sizes with P-values for development of GBD were generated. We identify two new loci associated with GBD, GCKR rs1260326:T>C (P=5.88 × 10−7, ß=−0.146) and TTC39B rs686030:C>A (P=6.95x10−7, ß=0.271) and detect four independent SNP effects in ABCG8 rs4953023:G>A (P=7.41 × 10−47, ß=0.734), ABCG8 rs4299376:G>T (P=2.40 × 10−18, ß=0.278), ABCG5 rs6544718:T>C (P=2.08 × 10−14, ß=0.044) and ABCG5 rs6720173:G>C (P=3.81 × 10−12, ß=0.262) in conditional analyses taking genotypes of rs4953023:G>A as a covariate. We also delineate the risk effects among many genotypes known to influence lipids. These data, from the largest GBD genetic study to date, show that specific, mainly hepatocyte-centred, components of lipid metabolism are important to GBD risk in women. We discuss the potential pharmaceutical implications of our findings.
doi:10.1038/ejhg.2015.63
PMCID: PMC4681116  PMID: 25920552
6.  Lipids, obesity and gallbladder disease in women: insights from genetic studies using the cardiovascular gene-centric 50K SNP array 
Gallbladder disease (GBD) has an overall prevalence of 10-40% depending on factors such as age, gender, population, obesity and diabetes, and represents a major economic burden. While gallstones are composed of cholesterol by-products and are associated with obesity, presumed causal pathways remain unproven, although BMI reduction is typically recommended. We performed genetic studies to discover candidate genes and define pathways involved in GBD. We genotyped 15,241 women of European ancestry from three cohorts, including 3,216 with GBD, using the Human cardiovascular disease (HumanCVD) BeadChip (Illumina, San Diego, CA) containing up to ~53,000 SNPs. Effect sizes with p values for development of GBD were generated. We identify two new loci associated with GBD, GCKR rs1260326:T>C (P=5.88×10−7, ß=−0.146) and TTC39B rs686030:C>A (P=6.95×10−7, ß=0.271) and detect four independent SNP effects in ABCG8 rs4953023:G>A (P=7.41×10−47, ß=0.734), ABCG8 rs4299376:G>T (P=2.40×10−18, ß=0.278), ABCG5 rs6544718:T>C (P=2.08×10−14, ß=0.044) and ABCG5 rs6720173:G>C (P=3.81×10−12, ß=0.262) in conditional analyses taking genotypes of rs4953023:G>A as a covariate. We also delineate the risk effects among many genotypes known to influence lipids. These data, from the largest GBD genetic study to date, show that specific, mainly hepatocyte-centred, components of lipid metabolism are important to GBD risk in women. We discuss the potential pharmaceutical implications of our findings.
doi:10.1038/ejhg.2015.63
PMCID: PMC4681116  PMID: 25920552
gallbladder disease; genetics; lipids; women; cardiovascular gene-centric 50K SNP array
7.  Control of Blood Pressure and Risk Attenuation: Post Trial Follow-Up of Randomized Groups 
PLoS ONE  2015;10(11):e0140550.
Background
Evidence on long term effectiveness of public health strategies for lowering blood pressure (BP) is scarce. In the Control of Blood Pressure and Risk Attenuation (COBRA) Trial, a 2 x 2 factorial, cluster randomized controlled trial, the combined home health education (HHE) and trained general practitioner (GP) intervention delivered over 2 years was more effective than no intervention (usual care) in lowering systolic BP among adults with hypertension in urban Pakistan. However, it was not clear whether the effect would be sustained after the cessation of intervention. We conducted 7 years follow-up inclusive of 5 years of post intervention period of COBRA trial participants to assess the effectiveness of the interventions on BP during extended follow-up.
Methods
A total of 1341 individuals 40 years or older with hypertension (systolic BP 140 mm Hg or greater, diastolic BP 90 mm Hg or greater, or already receiving treatment) were followed by trained research staff masked to randomization status. BP was measured thrice with a calibrated automated device (Omron HEM-737 IntelliSense) in the sitting position after 5 minutes of rest. BP measurements were repeated after two weeks. Generalized estimating equations (GEE) were used to analyze the primary outcome of change in systolic BP from baseline to 7- year follow-up. The multivariable model was adjusted for clustering, age at baseline, sex, baseline systolic and diastolic BP, and presence of diabetes.
Findings
After 7 years of follow-up, systolic BP levels among those randomised to combined HHE plus trained GP intervention were significantly lower (2.1 [4.1–0.1] mm Hg) compared to those randomised to usual care, (P = 0.04). Participants receiving the combined intervention compared to usual care had a greater reduction in LDL-cholesterol (2.7 [4.8 to 0.6] mg/dl.
Conclusions
The benefit in systolic BP reduction observed in the original cohort assigned to the combined intervention was attenuated but still evident at 7- year follow-up. These findings highlight the potential for scaling-up simple strategies for cardiovascular risk reduction in low- and middle- income countries.
Trial Registration
ClinicalTrials.gov NCT00327574
doi:10.1371/journal.pone.0140550
PMCID: PMC4634976  PMID: 26540210
8.  Associations between active travel and adiposity in rural India and Bangladesh: a cross-sectional study 
BMC Public Health  2015;15:1087.
Background
Data on use and health benefits of active travel in rural low- and middle- income country settings are sparse. We aimed to examine correlates of active travel, and its association with adiposity, in rural India and Bangladesh.
Methods
Cross sectional study of 2,122 adults (≥18 years) sampled in 2011–13 from two rural sites in India (Goa and Chennai) and one in Bangladesh (Matlab). Logistic regression was used to examine whether ≥150 min/week of active travel was associated with socio-demographic indices, smoking, oil/butter consumption, and additional physical activity. Adjusting for these same factors, associations between active travel and BMI, waist circumference and waist-to-hip ratio were examined using linear and logistic regression.
Results
Forty-six percent of the sample achieved recommended levels of physical activity (≥150 min/week) through active travel alone (range: 33.1 % in Matlab to 54.8 % in Goa). This was more frequent among smokers (adjusted odds ratio 1.36, 95 % confidence interval 1.07–1.72; p = 0.011) and those that spent ≥150 min/week in work-based physical activity (OR 1.71, 1.35–2.16; p < 0.001), but less frequent among females than males (OR 0.25, 0.20–0.31; p < 0.001). In fully adjusted analyses, ≥150 min/week of active travel was associated with lower BMI (adjusted coefficient −0.39 kg/m2, −0.77 to −0.02; p = 0.037) and a lower likelihood of high waist circumference (OR 0.77, 0.63–0.96; p = 0.018) and high waist-to-hip ratio (OR 0.72, 0.58–0.89; p = 0.002).
Conclusions
Use of active travel for ≥150 min/week was associated with being male, smoking, and higher levels of work-based physical activity. It was associated with lower BMI, and lower risk of a high waist circumference or high waist-to-hip ratio. Promotion of active travel is an important component of strategies to address the growing prevalence of overweight in rural low- and middle- income country settings.
Electronic supplementary material
The online version of this article (doi:10.1186/s12889-015-2411-0) contains supplementary material, which is available to authorized users.
doi:10.1186/s12889-015-2411-0
PMCID: PMC4619428  PMID: 26498367
Active commuting; Exercise; Overweight; Obesity; Body mass index; South Asia
9.  Urban-Rural Differences in Bone Mineral Density: A Cross Sectional Analysis Based on the Hyderabad Indian Migration Study 
PLoS ONE  2015;10(10):e0140787.
Background
Fracture risk is rising in countries undergoing rapid rural to urban migration, but whether this reflects an adverse effect of urbanization on intrinsic bone strength, as reflected by bone mineral density (BMD), is currently unknown.
Methods
Lumbar spine (LS) and total hip (TH) BMD, and total body fat and lean mass, were obtained from DXA scans performed in the Hyderabad arm of the Indian Migration Study (54% male, mean age 49 years). Sib-pair comparisons were performed between rural-urban migrants (RUM) and rural non-migrated (RNM) siblings (N = 185 sib-pairs).
Results
In analyses adjusted for height, gender, age and occupation, rural to urban migration was associated with higher lumbar and hip BMD and greater predicted hip strength; ΔLS BMD 0.030 (0.005, 0.055) g/cm2, ΔTH BMD 0.044 (0.024; 0.064) g/cm2, Δcross-sectional moment of inertia 0.162 (0.036, 0.289) cm4. These differences were largely attenuated after adjusting for body composition, insulin levels and current lifestyle factors ie. years of smoking, alcohol consumption and moderate to vigorous physical activity. Further analyses suggested that differences in lean mass, and to a lesser extent fat mass, largely explained the BMD differences which we observed.
Conclusions
Rural to urban migration as an adult is associated with higher BMD and greater predicted hip strength, reflecting associated alterations in body composition. It remains to be seen how differences in BMD between migration groups will translate into fracture risk in becoming years.
doi:10.1371/journal.pone.0140787
PMCID: PMC4618924  PMID: 26484878
10.  Intra-household evaluations of alcohol abuse in men with depression and suicide in women: A cross-sectional community-based study in Chennai, India 
BMC Public Health  2015;15:636.
Background
Harmful effects of alcohol abuse are well documented for drinkers, and adverse effects are also reported for the physical and emotional well-being of family members, with evidence often originating from either drinkers or their families in clinic-based settings. This study evaluates intra-household associations between alcohol abuse in men, and depression and suicidal attempts in women, in community-based settings of Chennai, India.
Methods
This community-based cross-sectional study of chronic disease risk factors and outcomes was conducted in n = 259 households and n = 1053 adults (aged 15 years and above) in rural and urban Chennai. The Alcohol Use Disorder Identification Test (AUDIT) score was used to classify alcohol consumption into ‘low-risk', ‘harmful’, ‘hazardous’ and ‘alcohol dependence’ drinking and the Patient Health Questionnaire (PHQ-9) score to classify depression as ‘mild’, ‘moderate’, ‘moderate-severe’ and ‘severe’. Multivariate logistic regression models estimated the association of depression in women with men’s drinking patterns in the same household.
Results
A significant 2.5-fold increase in any depression (PHQ-9 ≥ 5) was observed in men who were ‘alcohol-dependent’ compared to non-drinkers (OR = 2.53; 95 % CI: 1.26, 5.09). However, there was no association between men’s drinking behavior and depression in women of the same household, although suicidal attempts approached a significant dose–response relationship with increasing hazard-level of men’s drinking (p = 0.08).
Conclusion
No significant intra-household association was observed between men’s alcohol consumption and women’s depression, though an increasing (non-significant) trend was associated with suicidal attempts. Complex relationships between suicidal attempts and depression in women and male abusive drinking require further exploration, with an emphasis on intra-household mechanisms and pathways.
doi:10.1186/s12889-015-1864-5
PMCID: PMC4702375  PMID: 26163294
Alcohol; Depression; Suicidal attempt; Spouse; India; NCDs
11.  What do Indian children drink when they do not receive water? Statistical analysis of water and alternative beverage consumption from the 2005–2006 Indian National Family Health Survey 
BMC Public Health  2015;15:612.
Background
Over 1.2 billion people lack access to clean water. However, little is known about what children drink when there is no clean water. We investigated the prevalence of receiving no water and what Indian children drink instead.
Methods
We analysed children’s beverage consumption using representative data from India’s National Family and Health Survey (NFHS-3, 2005–2006). Consumption was based on mothers’ reports (n = 22,668) for children aged 6–59 months (n = 30,656).
Results
About 10 % of Indian children had no water in the last 24 h, corresponding to 12,700,000 children nationally, (95 % CI: 12,260,000 to 13,200,000). Among children who received no water, 23 % received breast or fresh milk and 24 % consumed formula, “other liquid”, juice, or two or more beverages. Children over 2 were more likely to consume non-milk beverages, including tea, coffee, and juice than those under 2 years. Those in the lowest two wealth quintiles were 16 % less likely to have received water (OR = 0.84; 95 % CI: 0.74 to 0.96). Compared to those living in households with bottled, piped, or tanker water, children were significantly less likely to receive water in households using well water (OR = 0.75; 95 % CI: 0.64 to 0.89) or river, spring, or rain water (OR = 0.70; 95 % CI: 0.53 to 0.92) in the last 24 h.
Conclusions
About 13 million Indian children aged 6–59 months received no water in the last 24 h. Further research is needed to assess the risks potentially arising from insufficient water, caffeinated beverages, and high sugar drinks at early stages of life.
Electronic supplementary material
The online version of this article (doi:10.1186/s12889-015-1946-4) contains supplementary material, which is available to authorized users.
doi:10.1186/s12889-015-1946-4
PMCID: PMC4491259  PMID: 26143185
12.  Food Price Spikes Are Associated with Increased Malnutrition among Children in Andhra Pradesh, India123 
The Journal of Nutrition  2015;145(8):1942-1949.
Background: Global food prices have risen sharply since 2007. The impact of food price spikes on the risk of malnutrition in children is not well understood.
Objective: We investigated the associations between food price spikes and childhood malnutrition in Andhra Pradesh, one of India’s largest states, with >85 million people. Because wasting (thinness) indicates in most cases a recent and severe process of weight loss that is often associated with acute food shortage, we tested the hypothesis that the escalating prices of rice, legumes, eggs, and other staples of Indian diets significantly increased the risk of wasting (weight-for-height z scores) in children.
Methods: We studied periods before (2006) and directly after (2009) India’s food price spikes with the use of the Young Lives longitudinal cohort of 1918 children in Andhra Pradesh linked to food price data from the National Sample Survey Office. Two-stage least squares instrumental variable models assessed the relation of food price changes to food consumption and wasting prevalence (weight-for-height z scores).
Results: Before the 2007 food price spike, wasting prevalence fell from 19.4% in 2002 to 18.8% in 2006. Coinciding with India’s escalating food prices, wasting increased significantly to 28.0% in 2009. These increases were concentrated among low- (χ2: 21.6, P < 0.001) and middle- (χ2: 25.9, P < 0.001) income groups, but not among high-income groups (χ2: 3.08, P = 0.079). Each 10.0 rupee ($0.170) increase in the price of rice/kg was associated with a drop in child-level rice consumption of 73.0 g/d (β: −7.30; 95% CI: −10.5, −3.90). Correspondingly, lower rice consumption was significantly associated with lower weight-for-height z scores (i.e., wasting) by 0.005 (95% CI: 0.001, 0.008), as seen with most other food categories.
Conclusion: Rising food prices were associated with an increased risk of malnutrition among children in India. Policies to help ensure the affordability of food in the context of economic growth are likely critical for promoting children’s nutrition.
doi:10.3945/jn.115.211250
PMCID: PMC4516769  PMID: 26136589
food price spikes; food consumption; weight-for-height z scores; child nutrition; India
13.  Why Do Thin People Have Elevated All-Cause Mortality? Evidence on Confounding and Reverse Causality in the Association of Adiposity and COPD from the British Women’s Heart and Health Study 
PLoS ONE  2015;10(4):e0115446.
Low adiposity has been linked to elevated mortality from several causes including respiratory disease. However, this could arise from confounding or reverse causality. We explore the association between two measures of adiposity (BMI and WHR) with COPD in the British Women’s Heart and Health Study including a detailed assessment of the potential for confounding and reverse causality for each adiposity measure. Low BMI was found to be associated with increased COPD risk while low WHR was not (OR = 2.2; 95% CI 1.3 – 3.1 versus OR = 1.2; 95% CI 0.7 – 1.6). Potential confounding variables (e.g. smoking) and markers of ill-health (e.g. unintentional weight loss) were found to be higher in low BMI but not in low WHR. Women with low BMI have a detrimental profile across a broad range of health markers compared to women with low WHR, and women with low WHR do not appear to have an elevated COPD risk, lending support to the hypothesis that WHR is a less confounded measure of adiposity than BMI. Low adiposity does not in itself appear to increase the risk of respiratory disease, and the apparent adverse consequences of low BMI may be due to reverse causation and confounding.
doi:10.1371/journal.pone.0115446
PMCID: PMC4401726  PMID: 25884834
14.  Fixed-dose combination therapy for the prevention of cardiovascular disease 
Background
Cardiovascular disease (CVD) is the leading cause of death and disability worldwide, yet CVD risk factor control and secondary prevention rates remain low. A fixed-dose combination of blood pressure and cholesterol lowering and antiplatelet treatments into a single pill, or polypill, has been proposed as one strategy to reduce the global burden of CVD by up to 80% given its potential for better adherence and lower costs.
Objectives
To determine the effectiveness of fixed-dose combination therapy on reducing fatal and non-fatal CVD events and on improving blood pressure and lipid CVD risk factors for both primary and secondary prevention of CVD. We also aimed to determine discontinuation rates, adverse events, health-related quality of life, and costs of fixed-dose combination therapy.
Search methods
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library(2013, Issue 6), MEDLINE Ovid (1946 to week 2 July 2013), EMBASE Ovid (1980 to Week 28 2013), ISI Web of Science (1970 to 19 July 2013), and the Database of Abstracts of Reviews of Effects (DARE), Health Technology Assessment Database (HTA), and Health Economics Evaluations Database (HEED) (2011, Issue 4) in The Cochrane Library. We used no language restrictions.
Selection criteria
We included randomised controlled trials of a fixed-dose combination therapy including at least one blood pressure lowering and one lipid lowering component versus usual care, placebo, or a single drug active component for any treatment duration in adults ≥ 18 years old with no restrictions on presence or absence of pre-existing cardiovascular disease.
Data collection and analysis
Three review authors independently selected studies for inclusion and extracted the data. We evaluated risk of bias using the Cochrane risk of bias assessment tool. We sought to include outcome data on all-cause mortality, fatal and non-fatal CVD events, adverse events, changes in systolic and diastolic blood pressure, total and low density lipoprotein (LDL) cholesterol concentrations, discontinuation rates, quality of life, and costs. We calculated risk ratios (RR) for dichotomous data and weighted mean differences (MD) for continuous data with 95% confidence intervals (CI) using fixed-effect models when heterogeneity was low (I2 < 50%) and random-effects models when heterogeneity was high (I2 > 50%).
Main results
We found nine randomised controlled trials with a total of 7047 participants. Seven of the nine trials evaluated the effects of fixed-dose combination therapy on primary CVD prevention, and the trial length ranged from six weeks to 15 months. We found a moderate to high risk of bias in the domains of selection, performance, detection, attrition, and other types of bias in five of the nine trials. Compared with the comparator groups, the effects of the fixed-dose combination treatment on mortality (1.2% versus 1.0%, RR 1.26, 95% CI 0.67 to 2.38, N = 3465) and cardiovascular events (4.0% versus 2.9%, RR 1.38, 95% CI 0.91 to 2.10, N = 2479) were uncertain (low quality evidence). The low event rates for these outcomes, limited availability of data as only two out of nine trials reported on these outcomes, and a high risk of bias in at least one domain suggest that these results should not be viewed with confidence. Adverse events were common in both the intervention (30%) and comparator (24%) groups, with participants randomised to fixed-dose combination therapy being 20% (95% CI 9% to 30%) more likely to report an adverse event. Notably, no serious adverse events were reported. Compared with placebo, the rate of discontinuation among participants randomised to fixed-dose combination was higher (14% versus 11%, RR 1.26 95% CI 1.02 to 1.55). The weighted mean differences in systolic and diastolic blood pressure between the intervention and control arms were -7.05 mmHg (95% CI -10.18 to -3.87) and -3.65 mmHg (95% CI -5.44 to -1.85), respectively. The weighted mean differences (95% CI) in total and LDL cholesterol between the intervention and control arms were -0.75 mmol/L (95% CI -1.05 to -0.46) and -0.81 mmol/L (95% CI -1.09 to -0.53), respectively. There was a high degree of statistical heterogeneity in comparisons of blood pressure and lipids (I2 ≥ 70% for all) that could not be explained, so these results should be viewed with caution. Fixed-dose combination therapy improved adherence to a multi-drug strategy by 33% (26% to 41%) compared with usual care, but this comparison was reported in only one study. The effects of fixed-dose combination therapy on quality of life are uncertain, though these results were reported in only one trial. No trials reported costs.
Authors' conclusions
Compared with placebo, single drug active component, or usual care, the effects of fixed-dose combination therapy on all-cause mortality or CVD events are uncertain; only few trials report these outcomes and the included trials were primarily designed to observe changes in CVD risk factor levels rather than clinical events. Reductions in blood pressure and lipid parameters are generally lower than those previously projected, though substantial heterogeneity of results exists. Fixed-dose combination therapy is associated with modest increases in adverse events compared with placebo, single drug active component, or usual care but may be associated with improved adherence to a multidrug regimen. Ongoing trials of fixed-dose combination therapy will likely inform key outcomes.
doi:10.1002/14651858.CD009868.pub2
PMCID: PMC4083498  PMID: 24737108
15.  Associations between diet, physical activity and body fat distribution: a cross sectional study in an Indian population 
BMC Public Health  2015;15:281.
Background
Obesity is a growing health problem in India and worldwide, due to changes in lifestyle. This study aimed to explore the independent associations between dietary and physical activity exposure variables and total body fat and distribution in an Indian setting.
Methods
Individuals who had participated in the Indian Migration Study (IMS) or the Andhra Pradesh Children And Parents' Study (APCAPS), were invited to participate in the Hyderabad DXA Study. Total and abdominal body fat of study participants was measured using DXA scans. Diet and physical activity (PA) levels were measured using questionnaires.
Results
Data on 2208 participants was available for analysis; mean age was 49 yrs in IMS, 21 yrs in APCAPS. Total energy intake was positively associated with total body fat in the APCAPS sample: a 100 kcal higher energy intake was associated with 45 g higher body fat (95% CI 22, 68). In the IMS sample no association was found with total energy intake, but there was a positive association with percent protein intake (1% higher proportion of energy from protein associated with 509 g (95% CI 138,880) higher total body fat). Broadly the same pattern of associations was found with proportion of fat in the abdominal region as the outcome. PA was inversely associated with total body fat in both populations (in APCAPS, one MET-hour higher activity was associated with 46 g (95% CI 12, 81) less body fat; in the IMS it was associated with 145 g less body fat (95% CI 73, 218)). An inverse association was observed between PA and percentage abdominal fat in the IMS but no association was seen in the APCAPS population.
Conclusions
In this Indian population, there was an inverse association between PA and body fat. Associations between body fat and dietary variables differed between the younger APCAPS population and older IMS population. Further longitudinal research is needed to elucidate causality and directions of these associations across the life course.
Electronic supplementary material
The online version of this article (doi:10.1186/s12889-015-1550-7) contains supplementary material, which is available to authorized users.
doi:10.1186/s12889-015-1550-7
PMCID: PMC4381479  PMID: 25885589
Obesity; Body fat; Diet; Physical activity; India
16.  Socio-economic patterning of cardiometabolic risk factors in rural and peri-urban India: Andhra Pradesh children and parents study (APCAPS) 
Aim
To assess the prevalence of cardiometabolic risk factors by socio-economic position (SEP) in rural and peri-urban Indian population.
Subjects and methods
Cross-sectional survey of 3,948 adults (1,154 households) from Telangana (2010–2012) was conducted to collect questionnaire-based data, physical measurements and fasting blood samples. We compared the prevalence of risk factors and their clustering by SEP adjusting for age using the Mantel Hansel test.
Results
Men and women with no education had higher prevalence of increased waist circumference (men: 8 vs. 6.4 %, P < 0.001; women: 20.9 vs. 12.0 %, P = 0.01), waist-hip ratio (men: 46.5 vs. 25.8 %, P = 0.003; women: 58.8 vs. 29.2 %, P = 0.04) and regular alcohol intake (61.7 vs. 32.5 %, P < 0.001; women: 25.7 vs. 3.8 %, P < 0.001) than educated participants. Unskilled participants had higher prevalence of regular alcohol intake (men: 57.7 vs. 38.7 %, P = 0.001; women: 28.3 vs. 7.3 %, P < 0.001). In contrast, participants with a higher standard of living index had higher prevalence of diabetes (top third vs. bottom third: men 5.2 vs. 3.5 %, P = 0.004; women 5.5 vs. 2.4 %, P = 0.003), hyperinsulinemia (men 29.5 vs. 16.3 %, P = 0.002; women 31.1 vs. 14.3 %, P < 0.001), obesity (men 23.3 vs. 10.6 %, P < 0.001; women 25.9 vs. 12.8 %, P < 0.001), and raised LDL (men 16.8 vs. 11.4 %, P = 0.001; women 21.3 vs. 14.0 %, P < 0.001).
Conclusions
Cardiometabolic risk factors are common in rural India but do not show a consistent association with SEP except for higher prevalence of smoking and regular alcohol intake in lower SEP group. Strategies to address the growing burden of cardiometabolic diseases in urbanizing rural India should be assessed for their potential impact on social inequalities in health.
doi:10.1007/s10389-015-0662-y
PMCID: PMC4434856  PMID: 26000232
Socioeconomic position; Status; Cardiovascular; Metabolic disease; Risk factors
17.  Are estimates of socioeconomic inequalities in chronic disease artefactually narrowed by self-reported measures of prevalence in low-income and middle-income countries? Findings from the WHO-SAGE survey 
Background
The use of self-reported measures of chronic disease may substantially underestimate prevalence in low-income and middle-income country settings, especially in groups with lower socioeconomic status (SES). We sought to determine whether socioeconomic inequalities in the prevalence of non-communicable chronic diseases (NCDs) differ if estimated by using symptom-based or criterion-based measures compared with self-reported physician diagnoses.
Methods
Using population-representative data sets of the WHO Study of Global Ageing and Adult Health (SAGE), 2007–2010 (n=42 464), we calculated wealth-related and education-related concentration indices of self-reported diagnoses and symptom-based measures of angina, hypertension, asthma/chronic lung disease, visual impairment and depression in three ‘low-income and lower middle-income countries’—China, Ghana and India—and three ‘upper-middle-income countries’—Mexico, Russia and South Africa.
Results
SES gradients in NCD prevalence tended to be positive for self-reported diagnoses compared with symptom-based/criterion-based measures. In China, Ghana and India, SES gradients were positive for hypertension, angina, visual impairment and depression when using self-reported diagnoses, but were attenuated or became negative when using symptom-based/criterion-based measures. In Mexico, Russia and South Africa, this distinction was not observed consistently. For example, concentration index of self-reported versus symptom-based angina were: in China: 0.07 vs −0.11, Ghana: 0.04 vs −0.21, India: 0.02 vs −0.16, Mexico: 0.19 vs −0.22, Russia: −0.01 vs −0.02 and South Africa: 0.37 vs 0.02.
Conclusions
Socioeconomic inequalities in NCD prevalence tend to be artefactually positive when using self-report compared with symptom-based or criterion-based diagnostic criteria, with greater bias occurring in low-income countries. Using standardised, symptom-based measures would provide more valid estimates of NCD inequalities.
doi:10.1136/jech-2014-204621
PMCID: PMC4345525  PMID: 25550454
Epidemiology of chronic non communicable diseases; INEQUALITIES; PUBLIC HEALTH
18.  Is vulnerability to cardiometabolic disease in Indians mediated by abdominal adiposity or higher body adiposity 
BMC Public Health  2014;14:1239.
Background
Indians may be particularly vulnerable to cardiometabolic disease, potentially due to higher body fat for a given BMI, or a tendency towards depositing abdominal adiposity. The aim of the study is to assess whether different measures of the distribution of adiposity (abdominal versus whole body) or amount of adiposity (DXA versus traditional anthropometric) are better at predicting prevalent cardiometabolic risk markers in an Indian population.
Methods
Participants were recruited from the Indian Migration Study (IMS) and the Andhra Pradesh Children and Parent Study (APCAPS). Participants attended a clinic in Hyderabad, India, January 2009-December 2010. Adiposity was measured by conventional anthropometry (including weight, height, waist) and DXA scanning (whole body and abdominal). Blood samples were taken and assessed for fasting plasma glucose, insulin, cholesterol, and triglycerides and blood pressure was measured. Lifestyle data were collected by questionnaire.
Results
We invited 4 617 participants to the clinic (1 995 IMS; 2 622 APCAPS) and examined 918 from IMS (46%) and 1 451 from APCAPS (55%). There were strong and consistent relationships between adiposity and cardiometabolic risk factors. Cardiometabolic risk factors did not appear to be more strongly associated with DXA measures as opposed to BMI, or skinfold measures of body fat. There was some evidence that WHR was more closely related to diabetes than total body adiposity, but this was not apparent for the other measures of abdominal adiposity (DXA measures, waist circumference) or other cardiometablic risk factors.
Conclusions
No strong evidence supports that DXA measures or abdominal measures of adiposity are better at predicting the prevalence of cardiometabolic risk factors in comparison to BMI.
Electronic supplementary material
The online version of this article (doi:10.1186/1471-2458-14-1239) contains supplementary material, which is available to authorized users.
doi:10.1186/1471-2458-14-1239
PMCID: PMC4289237  PMID: 25438835
Adiposity; India; Cardiometabolic; Diabetes; Hypertension; Cardiovascular; Dual-energy X-ray absorptiometry
19.  Variation in the SLC23A1 gene does not influence cardiometabolic outcomes to the extent expected given its association with l-ascorbic acid1234 
Background: Observational studies showed that circulating l-ascorbic acid (vitamin C) is inversely associated with cardiometabolic traits. However, these studies were susceptible to confounding and reverse causation.
Objectives: We assessed the relation between l-ascorbic acid and 10 cardiometabolic traits by using a single nucleotide polymorphism in the solute carrier family 23 member 1 (SLC23A1) gene (rs33972313) associated with circulating l-ascorbic acid concentrations. The observed association between rs33972313 and cardiometabolic outcomes was compared with that expected given the rs33972313-l-ascorbic acid and l-ascorbic acid–outcome associations.
Design: A meta-analysis was performed in the following 5 independent studies: the British Women's Heart and Health Study (n = 1833), the MIDSPAN study (n = 1138), the Ten Towns study (n = 1324), the British Regional Heart Study (n = 2521), and the European Prospective Investigation into Cancer (n = 3737).
Results: With the use of a meta-analysis of observational estimates, inverse associations were shown between l-ascorbic acid and systolic blood pressure, triglycerides, and the waist-hip ratio [the strongest of which was the waist-hip ratio (−0.13-SD change; 95% CI: −0.20-, −0.07-SD change; P = 0.0001) per SD increase in l-ascorbic acid], and a positive association was shown with high-density lipoprotein (HDL) cholesterol. The variation at rs33972313 was associated with a 0.18-SD (95% CI: 0.10-, 0.25-SD; P = 3.34 × 10−6) increase in l-ascorbic acid per effect allele. There was no evidence of a relation between the variation at rs33972313 and any cardiometabolic outcome. Although observed estimates were not statistically different from expected associations between rs33972313 and cardiometabolic outcomes, estimates for low-density lipoprotein cholesterol, HDL cholesterol, triglycerides, glucose, and body mass index were in the opposite direction to those expected.
Conclusions: The nature of the genetic association exploited in this study led to limited statistical application, but despite this, when all cardiometabolic traits were assessed, there was no evidence of any trend supporting a protective role of l-ascorbic acid. In the context of existing work, these results add to the suggestion that observational relations between l-ascorbic acid and cardiometabolic health may be attributable to confounding and reverse causation.
doi:10.3945/ajcn.114.092981
PMCID: PMC4266888  PMID: 25527764
l-ascorbic acid; cardiometabolic traits; confounding; genetic variants; reverse causation
20.  Exercise-based cardiac rehabilitation for coronary heart disease 
Background
The burden of coronary heart disease (CHD) worldwide is one of great concern to patients and healthcare agencies alike. Exercise-based cardiac rehabilitation aims to restore patients with heart disease to health.
Objectives
To determine the effectiveness of exercise-based cardiac rehabilitation (exercise training alone or in combination with psychosocial or educational interventions) on mortality, morbidity and health-related quality of life of patients with CHD.
Search methods
RCTs have been identified by searching CENTRAL, HTA, and DARE (using The Cochrane Library Issue 4, 2009), as well as MEDLINE (1950 to December 2009), EMBASE (1980 to December 2009), CINAHL (1982 to December 2009), and Science Citation Index Expanded (1900 to December 2009).
Selection criteria
Men and women of all ages who have had myocardial infarction (MI), coronary artery bypass graft (CABG) or percutaneous transluminal coronary angioplasty (PTCA), or who have angina pectoris or coronary artery disease defined by angiography.
Data collection and analysis
Studies were selected and data extracted independently by two reviewers. Authors were contacted where possible to obtain missing information.
Main results
This systematic review has allowed analysis of 47 studies randomising 10,794 patients to exercise-based cardiac rehabilitation or usual care. In medium to longer term (i.e. 12 or more months follow-up) exercise-based cardiac rehabilitation reduced overall and cardiovascular mortality [RR 0.87 (95% CI 0.75, 0.99) and 0.74 (95% CI 0.63, 0.87), respectively], and hospital admissions [RR 0.69 (95% CI 0.51, 0.93)] in the shorter term (< 12 months follow-up) with no evidence of heterogeneity of effect across trials. Cardiac rehabilitation did not reduce the risk of total MI, CABG or PTCA. Given both the heterogeneity in outcome measures and methods of reporting findings, a meta-analysis was not undertaken for health-related quality of life. In seven out of 10 trials reporting health-related quality of life using validated measures was there evidence of a significantly higher level of quality of life with exercise-based cardiac rehabilitation than usual care.
Authors’ conclusions
Exercise-based cardiac rehabilitation is effective in reducing total and cardiovascular mortality (in medium to longer term studies) and hospital admissions (in shorter term studies) but not total MI or revascularisation (CABG or PTCA). Despite inclusion of more recent trials, the population studied in this review is still predominantly male, middle aged and low risk. Therefore, well-designed, and adequately reported RCTs in groups of CHD patients more representative of usual clinical practice are still needed. These trials should include validated health-related quality of life outcome measures, need to explicitly report clinical events including hospital admission, and assess costs and cost-effectiveness.
doi:10.1002/14651858.CD001800.pub2
PMCID: PMC4229995  PMID: 21735386
*Exercise Therapy; Coronary Disease [mortality; *rehabilitation]; Health Status; Myocardial Infarction [mortality; rehabilitation]; Myocardial Revascularization [statistics & numerical data]; Outcome Assessment (Health Care); Quality of Life; Randomized Controlled Trials as Topic; Female; Humans; Male
21.  Towards a comprehensive global approach to prevention and control of NCDs 
Background
The “25×25” strategy to tackle the global challenge of non-communicable diseases takes a traditional approach, concentrating on a few diseases and their immediate risk factors.
Discussion
We propose elements of a comprehensive strategy to address NCDs that takes account of the evolving social, economic, environmental and health care contexts, while developing mechanisms to respond effectively to local patterns of disease. Principles that underpin the comprehensive strategy include: (a) a balance between measures that address health at the individual and population level; (b) the need to identify evidence-based feasible and effective approaches tailored to low and middle income countries rather than exporting questionable strategies developed in high income countries; (c) developing primary health care as a universal framework to support prevention and treatment; (d) ensuring the ability to respond in real time to the complex adaptive behaviours of the global food, tobacco, alcohol and transport industries; (e) integrating evidence-based, cost-effective, and affordable approaches within the post-2015 sustainable development agenda; (f) determination of a set of priorities based on the NCD burden within each country, taking account of what it can afford, including the level of available development assistance; and (g) change from a universal “one-size fits all” approach of relatively simple prevention oriented approaches to more comprehensive multi-sectoral and development-oriented approaches which address both health systems and the determinants of NCD risk factors.
Summary
The 25×25 is approach is absolutely necessary but insufficient to tackle the the NCD disease burden of mortality and morbidity. A more comprehensive approach is recommended.
doi:10.1186/s12992-014-0074-8
PMCID: PMC4215019  PMID: 25348262
Non-communicable diseases; Prevention; Health systems
22.  The Association between a Vegetarian Diet and Cardiovascular Disease (CVD) Risk Factors in India: The Indian Migration Study 
PLoS ONE  2014;9(10):e110586.
Background
Studies in the West have shown lower cardiovascular disease (CVD) risk among people taking a vegetarian diet, but these findings may be confounded and only a minority selects these diets. We evaluated the association between vegetarian diets (chosen by 35%) and CVD risk factors across four regions of India.
Methods
Study participants included urban migrants, their rural siblings and urban residents, of the Indian Migration Study from Lucknow, Nagpur, Hyderabad and Bangalore (n = 6555, mean age-40.9 yrs). Information on diet (validated interviewer-administered semi-quantitative food frequency questionnaire), tobacco, alcohol, physical history, medical history, as well as blood pressure, fasting blood and anthropometric measurements were collected. Vegetarians ate no eggs, fish, poultry or meat. Using robust standard error multivariate linear regression models, we investigated the association of vegetarian diets with blood cholesterol, low density lipoprotein (LDL), high density lipoprotein (HDL), triglycerides, fasting blood glucose (FBG), systolic (SBP) and diastolic blood pressure (DBP).
Results
Vegetarians (32.8% of the study population) did not differ from non-vegetarians with respect to age, use of smokeless tobacco, body mass index, and prevalence of diabetes or hypertension. Vegetarians had a higher standard of living and were less likely to smoke, drink alcohol (p<0.0001) and were less physically active (p = 0.04). In multivariate analysis, vegetarians had lower levels of total cholesterol (β = −0.1 mmol/L (95% CI: −0.03 to −0.2), p = 0.006), triglycerides (β = −0.05 mmol/L (95% CI: −0.007 to −0.01), p = 0.02), LDL (β = −0.06 mmol/L (95% CI: −0.005 to −0.1), p = 0.03) and lower DBP (β = −0.7 mmHg (95% CI: −1.2 to −0.07), p = 0.02). Vegetarians also had decreases in SBP (β = −0.9 mmHg (95% CI: −1.9 to 0.08), p = 0.07) and FBG level (β = −0.07 mmol/L (95% CI: −0.2 to 0.01), p = 0.09) when compared to non-vegetarians.
Conclusion
We found beneficial association of vegetarian diet with cardiovascular risk factors compared to non-vegetarian diet.
doi:10.1371/journal.pone.0110586
PMCID: PMC4208768  PMID: 25343719
23.  Omega 3 fatty acids for prevention and treatment of cardiovascular disease 
Background
It has been suggested that omega 3 (W3, n-3 or omega-3) fats from oily fish and plants are beneficial to health.
Objectives
To assess whether dietary or supplemental omega 3 fatty acids alter total mortality, cardiovascular events or cancers using both RCT and cohort studies.
Search methods
Five databases including CENTRAL, MEDLINE and EMBASE were searched to February 2002. No language restrictions were applied. Bibliographies were checked and authors contacted.
Selection criteria
RCTs were included where omega 3 intake or advice was randomly allocated and unconfounded, and study duration was at least six months. Cohorts were included where a cohort was followed up for at least six months and omega 3 intake estimated.
Data collection and analysis
Studies were assessed for inclusion, data extracted and quality assessed independently in duplicate. Random effects meta-analysis was performed separately for RCT and cohort data.
Main results
Forty eight randomised controlled trials (36,913 participants) and 41 cohort analyses were included. Pooled trial results did not show a reduction in the risk of total mortality or combined cardiovascular events in those taking additional omega 3 fats (with significant statistical heterogeneity). Sensitivity analysis, retaining only studies at low risk of bias, reduced heterogeneity and again suggested no significant effect of omega 3 fats.
Restricting analysis to trials increasing fish-based omega 3 fats, or those increasing short chain omega 3s, did not suggest significant effects on mortality or cardiovascular events in either group. Subgroup analysis by dietary advice or supplementation, baseline risk of CVD or omega 3 dose suggested no clear effects of these factors on primary outcomes.
Neither RCTs nor cohorts suggested increased relative risk of cancers with higher omega 3 intake but estimates were imprecise so a clinically important effect could not be excluded.
Authors’ conclusions
It is not clear that dietary or supplemental omega 3 fats alter total mortality, combined cardiovascular events or cancers in people with, or at high risk of, cardiovascular disease or in the general population. There is no evidence we should advise people to stop taking rich sources of omega 3 fats, but further high quality trials are needed to confirm suggestions of a protective effect of omega 3 fats on cardiovascular health.
There is no clear evidence that omega 3 fats differ in effectiveness according to fish or plant sources, dietary or supplemental sources, dose or presence of placebo.
doi:10.1002/14651858.CD003177.pub2
PMCID: PMC4170890  PMID: 15495044
*Dietary Supplements; Cardiovascular Diseases [*diet therapy; mortality; prevention & control]; Fatty Acids, Omega-3 [*therapeutic use]; Randomized Controlled Trials as Topic; Humans
24.  Psychological interventions for coronary heart disease 
Background
Psychological interventions can form part of comprehensive cardiac rehabilitation programmes (CCR). These interventions may include stress management interventions, which aim to reduce stress, either as an end in itself or to reduce risk for further cardiac events in patients with heart disease.
Objectives
To determine the effectiveness of psychological interventions, in particular stress management interventions, on mortality and morbidity, psychological measures, quality of life, and modifiable cardiac risk factors, in patients with coronary heart disease (CHD).
Search strategy
We searched CCTR to December 2001 (Issue 4, 2001), MEDLINE 1999 to December 2001 and EMBASE 1998 to the end of 2001, PsychINFO and CINAHL to December 2001. In addition, searches of reference lists of papers were made and expert advice was sought.
Selection criteria
RCTs of non-pharmacological psychological interventions, administered by trained staff, either single modality interventions or a part of CCR with minimum follow up of 6 months. Adults of all ages with CHD (prior myocardial infarction, coronary artery bypass graft or percutaneous transluminal coronary angioplasty, angina pectoris or coronary artery disease defined by angiography). Stress management (SM) trials were identified and reported in combination with other psychological interventions and separately.
Data collection and analysis
Studies were selected, and data were abstracted, independently by two reviewers. Authors were contacted where possible to obtain missing information.
Main results
Thirty six trials with 12,841 patients were included. Of these, 18 (5242 patients) were SM trials. Quality of many trials was poor with the majority not reporting adequate concealment of allocation, and only 6 blinded outcome assessors. Combining the results of all trials showed no strong evidence of effect on total or cardiac mortality, or revascularisation. There was a reduction in the number of non-fatal reinfarctions in the intervention group (OR 0.78 (0.67, 0.90), but the two largest trials (with 4809 patients randomized) were null for this outcome, and there was statistical evidence of publication bias. Similar results were seen for the SM subgroup of trials. Provision of any psychological intervention or SM intervention caused small reductions in anxiety and depression. Few trials reported modifiable cardiac risk factors or quality of life.
Authors’ conclusions
Overall psychological interventions showed no evidence of effect on total or cardiac mortality, but did show small reductions in anxiety and depression in patients with CHD. Similar results were seen for SM interventions when considered separately. However, the poor quality of trials, considerable heterogeneity observed between trials and evidence of significant publication bias make the pooled finding of a reduction in non-fatal myocardial infarction insecure.
doi:10.1002/14651858.CD002902.pub2
PMCID: PMC4170898  PMID: 15106183
*Psychotherapy; Coronary Disease [mortality; *psychology; rehabilitation]; Stress, Psychological [*therapy]; Humans
25.  Do Girls Have a Nutritional Disadvantage Compared with Boys? Statistical Models of Breastfeeding and Food Consumption Inequalities among Indian Siblings 
PLoS ONE  2014;9(9):e107172.
Background
India is the only nation where girls have greater risks of under-5 mortality than boys. We test whether female disadvantage in breastfeeding and food allocation accounts for gender disparities in mortality.
Methods and Findings
Secondary, publicly available anonymized and de-identified data were used; no ethics committee review was required. Multivariate regression and Cox models were performed using Round 3 of India’s National Family and Health Survey (2005–2006; response rate = 93.5%). Models were disaggregated by birth order and sibling gender, and adjusted for maternal age, education, and fixed effects, urban residence, household deprivation, and other sociodemographics. Mothers’ reported practices of WHO/UNICEF recommendations for breastfeeding initiation, exclusivity, and total duration (ages 0–59 months), children’s consumption of 24 food items (6–59 months), and child survival (0–59 months) were examined for first- and secondborns (n = 20,395). Girls were breastfed on average for 0.45 months less than boys (95% CI: = 0.15 months to 0.75 months, p = 0.004). There were no gender differences in breastfeeding initiation (OR = 1.04, 95% CI: 0.97 to 1.12) or exclusivity (OR = 1.06, 95% CI: 0.99 to 1.14). Differences in breastfeeding cessation emerged between 12 and 36 months in secondborn females. Compared with boys, girls had lower consumption of fresh milk by 14% (95% CI: 79% to 94%, p = 0.001) and breast milk by 21% (95% CI: 70% to 90%, p<0.000). Each additional month of breastfeeding was associated with a 24% lower risk of mortality (OR = 0.76, 95% CI: 0.73 to 0.79, p<0.000). Girls’ shorter breastfeeding duration accounted for an 11% increased probability of dying before age 5, accounting for about 50% of their survival disadvantage compared with other low-income countries.
Conclusions
Indian girls are breastfed for shorter periods than boys and consume less milk. Future research should investigate the role of additional factors driving India’s female survival disadvantage.
doi:10.1371/journal.pone.0107172
PMCID: PMC4167551  PMID: 25229235

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