Paul Arora

Primary Prevention of Cardiovascular Mortality and Events With Statin Treatments A Network Meta-Analysis Involving More Than 65,000 Patients

OBJECTIVES This study aimed to evaluate the effectiveness of 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitors (statins) in primary prevention of cardiovascular events. BACKGROUND The role of statins is well established for secondary prevention of cardiovascular disease (CVD) clinical events and mortality. Little is known of their role in primary cardiovascular event prevention. METHODS We conducted comprehensive searches of 10 electronic databases from inception to May 2008. We contacted study investigators and maintained a comprehensive bibliography of statin studies. We included randomized trials of at least 12-month duration in predominantly primary prevention populations. Two reviewers independently extracted data in duplicate. We performed random-effects meta-analysis and meta-regression, calculated optimal information size, and conducted a mixed-treatment comparison analysis. RESULTS We included 20 randomized clinical trials. We pooled 19 trials (n = 63,899) for all-cause mortality and found a relative risk (RR) of 0.93 (95% confidence interval [CI]: 0.87 to 0.99, p = 0.03 [I(2) = 5%, 95% CI: 0% to 51%]). Eighteen trials (n = 59,469) assessed cardiovascular deaths (RR: 0.89, 95% CI: 0.81 to 0.98, p = 0.01 [I(2) = 0%, 95% CI: 0% to 41%]). Seventeen trials (n = 53,371) found an RR of 0.85 (95% CI: 0.77 to 0.95, p = 0.004 [I(2) = 61%, 95% CI: 38% to 77%]) for major cardiovascular events, and 17 trials (n = 52,976) assessed myocardial infarctions (RR: 0.77, 95% CI: 0.63 to 0.95, p = 0.01 [I(2) = 59%, 95% CI: 24% to 74%]). Incidence of cancer was not elevated in 10 trials (n = 45,469) (RR: 1.02, 95% CI: 0.94 to 1.11, p = 0.59 [I(2) = 0%, 95% CI: 0% to 46%]), nor was rhabdomyolysis (RR: 0.97, 95% CI: 0.25 to 3.83, p = 0.96 [I(2) = 0%, 95% CI: 0% to 40%]). Our analysis included a sufficient sample to reliably answer our primary outcome of CVD mortality. CONCLUSIONS Statins have a clear role in primary prevention of CVD mortality and major events.

Prevalence estimates of chronic kidney disease in Canada: results of a nationally representative survey

Background: Chronic kidney disease is an important risk factor for death and cardiovascular-related morbidity, but estimates to date of its prevalence in Canada have generally been extrapolated from the prevalence of end-stage renal disease. We used direct measures of kidney function collected from a nationally representative survey population to estimate the prevalence of chronic kidney disease among Canadian adults. Methods: We examined data for 3689 adult participants of cycle 1 of the Canadian Health Measures Survey (2007–2009) for the presence of chronic kidney disease. We also calculated the age-standardized prevalence of cardiovascular risk factors by chronic kidney disease group. We cross-tabulated the estimated glomerular filtration rate (eGFR) with albuminuria status. Results: The prevalence of chronic kidney disease during the period 2007–2009 was 12.5%, representing about 3 million Canadian adults. The estimated prevalence of stage 3–5 disease was 3.1% (0.73 million adults) and albuminuria 10.3% (2.4 million adults). The prevalence of diabetes, hypertension and hypertriglyceridemia were all significantly higher among adults with chronic kidney disease than among those without it. The prevalence of albuminuria was high, even among those whose eGFR was 90 mL/min per 1.73 m2 or greater (10.1%) and those without diabetes or hypertension (9.3%). Awareness of kidney dysfunction among adults with stage 3–5 chronic kidney disease was low (12.0%). Interpretation: The prevalence of kidney dysfunction was substantial in the survey population, including individuals without hypertension or diabetes, conditions most likely to prompt screening for kidney dysfunction. These findings highlight the potential for missed opportunities for early intervention and secondary prevention of chronic kidney disease.

Statin Therapy in Stroke Prevention: A Meta-analysis Involving 121,000 Patients

PURPOSE More than 120,000 patients now have taken part in randomized trials evaluating statin therapy for stroke prevention. We aimed to conduct a comprehensive review of all randomized trials and determine the therapeutic potential of statins for all strokes. METHODS We searched 10 electronic databases (from inception to December 2006). We additionally contacted study authors and authors of previous reviews. We extracted data on study characteristics and outcomes related to all-cause mortality, all-stroke incidence, specific type of strokes, and cholesterol changes. We pooled data using a random-effects model and conducted meta-regression. RESULTS We included 42 trials assessing statin therapy for all-stroke prevention (n=121,285), resulting in a pooled relative risk (RR) of 0.84 (95% confidence interval [CI], 0.79-0.91). The pooled RR of statin therapy for all-cause mortality (n=116,080) was 0.88 (95% CI, 0.83-0.93). Each unit increase in low-density lipoprotein (LDL) resulted in a 0.3% increased RR of death (P=.02). Seventeen trials evaluated statins on cardiovascular death (n=57,599, RR 0.81, 95% CI, 0.74-0.90), and 11 evaluated nonhemorrhagic cerebrovascular events (n=58,604, RR 0.81, 95% CI, 0.69-0.94). Eleven trials reported hemorrhagic stroke incidence (total n=54,334, RR 0.94, 95% CI, 0.68-1.30) and 21 trials reported on fatal strokes (total n=82,278, RR 0.99, 95% CI, 0.80-1.21). Only one trial reported on statin therapy for secondary prevention. CONCLUSIONS Statin therapy provides high levels of protection for all-cause mortality and nonhemorrhagic strokes. This overview reinforces the need to consider prolonged statin treatment in patients at high risk of major vascular events, but caution remains for patients at risk of bleeds.

Trends in HIV-1 in young adults in south India from 2000 to 2004: a prevalence study

BACKGROUND Major increases in HIV-1 prevalence in India have been predicted. Incident infections need to be tracked to understand the epidemics course, especially in some southern states of India where the epidemic is more advanced. To estimate incidence, we investigated the prevalence of HIV-1 in young people attending antenatal and sexually transmitted infection (STI) clinics in India. METHODS We analysed unlinked, anonymous HIV-1 prevalence data from 294 050 women attending 216 antenatal clinics and 58 790 men attending 132 STI clinics in 2000-04. Southern and northern states were analysed separately. FINDINGS The age-standardised HIV-1 prevalence in women aged 15-24 years in southern states fell from 1.7% to 1.1% in 2000-04 (relative reduction 35%; p(trend)<0.0001, yearly reduction 11%), but did not fall significantly in women aged 25-34 years. Reductions in women aged 15-24 years were seen in key demographic groups and were similar in sites tested continuously or in all sites. Prevalence in the north was about a fifth of that in the south, with no significant decreases (or increases) in 2000-04. Prevalence fell in men aged 20-29 years attending STI clinics in the south (p(trend)<0.0001), including those with ulcerative STIs (p(trend)=0.0008), but reductions were more modest in their northern counterparts. INTERPRETATION A reduction of more than a third in HIV-1 prevalence in 2000-04 in young women in south India seems realistic, and is not easily attributable to bias or to mortality. This fall is probably due to rising condom use by men and female sex workers in south India, and thus reduced transmission to wives. Expansion of peer-based condom and education programmes for sex workers remains a top priority to control HIV-1 in India.

Financial incentives and coverage of child health interventions: a systematic review and meta-analysis

BackgroundFinancial incentives are widely used strategies to alleviate poverty, foster development, and improve health. Cash transfer programs, microcredit, user fee removal policies and voucher schemes that provide direct or indirect monetary incentives to households have been used for decades in Latin America, Sub-Saharan Africa, and more recently in Southeast Asia. Until now, no systematic review of the impact of financial incentives on coverage and uptake of health interventions targeting children under 5 years of age has been conducted. The objective of this review is to provide estimates on the effect of six types of financial incentive programs: (i) Unconditional cash transfers (CT), (ii) Conditional cash transfers (CCT), (iii) Microcredit (MC), (iv) Conditional Microcredit (CMC), (v) Voucher schemes (VS) and (vi) User fee removal (UFR) on the uptake and coverage of health interventions targeting children under the age of five years.MethodsWe conducted systematic searches of a series of databases until September 1st, 2012, to identify relevant studies reporting on the impact of financial incentives on coverage of health interventions and behaviors targeting children under 5 years of age. The quality of the studies was assessed using the CHERG criteria. Meta-analyses were undertaken to estimate the effect when multiple studies meeting our inclusion criteria were available.ResultsOur searches resulted in 1671 titles identified 25 studies reporting on the impact of financial incentive programs on 5 groups of coverage indicators: breastfeeding practices (breastfeeding incidence, proportion of children receiving colostrum and early initiation of breastfeeding, exclusive breastfeeding for six months and duration of breastfeeding); vaccination (coverage of full immunization, partial immunization and specific antigens); health care use (seeking healthcare when child was ill, visits to health facilities for preventive reasons, visits to health facilities for any reason, visits for health check-up including growth control); management of diarrhoeal disease (ORS use during diarrhea episode, continued feeding during diarrhea, healthcare during diarrhea episode) and other preventive health interventions (iron supplementation, vitamin A, zinc supplementation, preventive deworming). The quality of evidence on the effect of financial incentives on breastfeeding practices was low but seems to indicate a potential positive impact on receiving colostrum, early initiation of breastfeeding, exclusive breastfeeding and mean duration of exclusive breastfeeding. There is no effect of financial incentives on immunization coverage although there was moderate quality evidence of conditional cash transfers leading to a small but non-significant increase in coverage of age-appropriate immunization. There was low quality evidence of impact of CCT on healthcare use by children under age 5 (Risk difference: 0.14 [95%CI: 0.03; 0.26]) as well as low quality evidence of an effect of user fee removal on use of curative health services (RD=0.62 [0.41; 0.82]).ConclusionsFinancial incentives may have potential to promote increased coverage of several important child health interventions, but the quality of evidence available is low. The more pronounced effects seem to be achieved by programs that directly removed user fees for access to health services. Some indication of effect were also observed for programs that conditioned financial incentives on participation in health education and attendance to health care visits. This finding suggest that the measured effect may be less a consequence of the financial incentive and more due to conditionalities addressing important informational barriers.

Vitamins D, C, and E in the prevention of type 2 diabetes mellitus: modulation of inflammation and oxidative stress.

The incidence of type 2 diabetes mellitus (T2DM) is increasing worldwide, and certain population subgroups are especially vulnerable to the disease. To reduce T2DM risk and progression at the population level, preventative strategies are needed that can be implemented on a population-wide scale with minimal cost and effort. Chronic low-grade inflammation resulting from oxidative stress and imbalances in the innate immune system has been associated with obesity, metabolic syndrome, and insulin resistance – critical stages in the development and progression of T2DM. Therefore, inflammation may play a causal role in the pathogenesis of T2DM, and reducing it via modulation of oxidative stress and the innate immune response could lead to a status of improved insulin sensitivity and delayed disease onset. Dietary supplementation with anti-inflammatory and antioxidant nutritional factors, such as micronutrients, might present a novel strategy toward the prevention and control of T2DM at the population level. This review examines current knowledge linking oxidation, inflammatory signaling pathways, and vitamin supplementation or intake to the risk of T2DM. The concept that micronutrients, via attenuation of inflammation, could be employed as a novel preventive measure for T2DM is evaluated in the context of its relevance to public health.

HIV mortality and infection in India: estimates from nationally representative mortality survey of 1.1 million homes

Objective To determine the rates of death and infection from HIV in India. Design Nationally representative survey of deaths. Setting 1.1 million homes in India. Population 123 000 deaths at all ages from 2001 to 2003. Main outcome measures HIV mortality and infection. Results HIV accounted for 8.1% (99% confidence interval 5.0% to 11.2%) of all deaths among adults aged 25-34 years. In this age group, about 40% of deaths from HIV were due to AIDS, 26% were due to tuberculosis, and the rest were attributable to other causes. Nationally, HIV infection accounted for about 100 000 (59 000 to 140 000) deaths or 3.2% (1.9% to 4.6%) of all deaths among people aged 15-59 years. Deaths from HIV were concentrated in the states and districts with higher HIV prevalence and in men. The mortality results imply an HIV prevalence at age 15-49 years of 0.26% (0.13% to 0.39%) in 2004, comparable to results from a 2005/6 household survey that tested for HIV (0.28%). Collectively, these data suggest that India had about 1.4-1.6 million HIV infected adults aged 15-49 years in 2004-6, about 40% lower than the official estimate of 2.3 million for 2006. All cause mortality increased in men aged 25-34 years between 1997 and 2002 in the states with higher HIV prevalence but declined after that. HIV prevalence in young pregnant women, a proxy measure of incidence in the general population, fell between 2000 and 2007. Thus, HIV mortality and prevalence may have fallen further since our study. Conclusion HIV attributable death and infection in India is substantial, although it is lower than previously estimated.

India's HIV-1 epidemic

Africas HIV-1 epidemic has, appropriately, received global attention. However, India stands to experience the greatest increase in absolute number of HIV-1 cases in the coming decades. As of 2004, at least 5 million people in India have been infected.[1][1] Preventive interventions to decrease

A Systematic Review and Meta-Analysis of Risk Factors for Sexual Transmission of HIV in India

Background Approximately 2.4 million people are living with HIV in India. This large disease burden, and potential for epidemic spread in some areas, demands a full understanding of transmission in that country. We wished to quantify the effects of key sexual risk factors for HIV infection for each gender and among high- and low-HIV risk populations in India. Methodology We conducted a systematic review of sexual risk factors for HIV infection from 35 published studies. Risk factors analyzed were: male circumcision/religion, Herpes Simplex Virus 2, syphilis, gonorrhoea, genital ulcer, multiple sexual partners and commercial sex. Studies were included if they met predetermined criteria. Data were extracted and checked by two researchers and random-effects meta analysis of effects was conducted. Heterogeneity in effect estimates was examined by I2 statistic. Publication bias was tested by Beggs test and funnel plots. Meta regression was used to assess effect modification by various study attributes. Results All risk factors were significantly associated with HIV status. The factor most strongly associated with HIV for both sexes was HSV-2 infection (ORmen: 5.87; 95%CI: 2.46–14.03; ORwomen: 6.44; 95%CI: 3.22–12.86). The effect of multiple sexual partners was similar among men (OR = 2.46; 95%CI: 1.91–3.17,) and women (OR = 2.02; 95%CI: 1.43–2.87) and when further stratified by HIV-risk group. The association between HSV-2 and HIV prevalence was consistently stronger than other STIs or self-reported genital ulcer. If the strong associations between HSV-2 and HIV were interpreted causally, these results implied that approximately half of the HIV infections observed in our study population were attributable to HSV-2 infection. Conclusions The risk factors examined in our analysis should remain targets of HIV prevention programs. Our results confirm that sexual risk factors for HIV infection continue to be an important part of Indian HIV epidemic 26 years after it began.

The association between obesity, cardiometabolic disease biomarkers, and innate immunity-related inflammation in Canadian adults

Introduction Obesity is associated with a state of chronic inflammation, and increased cardiometabolic disease risk. The present study examined the relationship between body mass index (BMI) and cardiometabolic and inflammatory biomarkers among normal weight, overweight, and obese Canadian adults. Methods Subjects (n = 1805, aged 18 to 79 years) from the Canadian Health Measures Survey (CHMS) were examined for associations between BMI, cardiometabolic markers (apolipoprotein [Apo] A1, ApoB, low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], total cholesterol, total cholesterol/HDL ratio [total:HDL-C ratio], triglycerides, and glycosylated hemoglobin [HbA1c]), inflammatory factors (C-reactive protein [CRP], fibrinogen, and homocysteine), and 25-hydroxyvitamin D [25(OH)D]. Bootstrap weights for variance and sampling weights for point estimates were applied to account for the complex survey design. Linear regression models adjusted for age, sex, physical activity, smoking status, and ethnicity (in addition to season of clinic visit, for vitamin D analyses only) were used to examine the association between cardiometabolic markers, inflammatory factors, and BMI in Canadian adults. Results All biomarkers were significantly associated with BMI (P ≤ 0.001). ApoA1 (β = −0.31, P < 0.0001), HDL-C (β = −0.61, P < 0.0001), and 25(OH)D (β = −0.25, P < 0.0001) were inversely associated with BMI, while all other biomarkers showed positive linear associations. Distinct patterns of association were noted among normal weight, overweight, and obese groups, excluding CRP which showed a significant positive association with BMI in the overall population (β = 2.80, P < 0.0001) and in the normal weight (β = 3.20, P = 0.02), overweight (β = 3.53, P = 0.002), and obese (β = 2.22, P = 0.0002) groups. Conclusions There is an apparent profile of cardiometabolic and inflammatory biomarkers that emerges as BMI increases from normal weight to obesity. Understanding these profiles may permit developing an effective approach for early risk prediction for cardiometabolic disease.