Differences In Risk Reduction Research Articles

Evaluating the predictive value of late gadolinium enhancement assessed by cardiac magnetic resonance on sudden cardiac death in patients selected for implantable cardioverter defibrillator and cardiac resynchronization therapy implantation: a systematic review and meta-analysis.

Late gadolinium enhancement (LGE) assessed by cardiovascular magnetic resonance (CMR) can evaluate myocardial scar associated with a higher risk of sudden cardiac death (SCD), which can guide the selection between cardiac resynchronization therapy with or without a defibrillator (CRT-P/CRT-D). Our aim was to investigate the association between LGE and SCD risk in patients with CRT using the LGE-CMR technique. We performed a systematic literature search using four databases. The target population was CRT candidates. The primary endpoint was SCD. The risk of bias was assessed using the QUIPS tool. Fifteen eligible articles were included with a total of 2494 patients, of whom 27%, 56%, and 19% had an implantable cardioverter defibrillator (ICD), CRT-D, and CRT-P, respectively. Altogether, 54.71% of the cohort was LGE positive, who had a 72% higher risk for SCD (HR 1.72; 95% CI 1.18-2.50) compared to LGE negatives. In non-ischemic patients, the proportion of LGE positivity was 46.6%, with a significantly higher risk for SCD as compared to LGE negatives (HR 2.42; 95% CI 1.99-2.94). The subgroup of CRT-only patients showed no difference between the LGE-positive vs. negative candidates (HR 1.17; 95% CI 0.82-1.68). Comparable SCD risk was observed between articles with short- (OR 7.47; 95% CI 0.54-103.12) vs. long-term (OR 6.15; 95% CI 0.96-39.45) follow-up time. LGE-CMR positivity was associated with an increased SCD risk; however, in CRT candidates, the difference in risk reduction between LGE positive vs. negative patients was statistically not significant, suggesting a role of reverse remodeling. LGE-CMR before device implantation could be crucial in identifying high-risk patients even in non-ischemic etiology.

Tracking the push towards extinction: combining dispersal and management data to monitor Asian longhorned beetle eradication in the U.S.

Based on the threat posed by the Asian longhorned beetle (Anoplophora glabripennis Motschulsky), many countries including the United States have adopted policies of eradication. The eradication of infestations that cover hundreds of square kilometers can require multiple visual surveys of millions of individual trees. At these scales, eradication may take several decades and span multiple beetle generations. During this period the infestation of new trees adds spatially-explicit risk to the landscape while surveys and the removal of infested trees reduce it. To track dynamic risk on the landscape we have developed the Asian Longhorned Beetle Hazard Management and Monitoring Tool. The geospatial tool combines data documenting; the locations, levels of infestation, and dates of detection of infested trees; the locations, methods, and timing of survey and host removal activities; and a reconstruction of beetle movement within the infested landscape to generate annual spatial estimates of infestation risk based on the combination of beetle dispersal and survey and host removal activities. The analyses of three eradication programs highlight similar patterns in risk through time with risk peaking at the time infestations are detected and declining as management activities slow beetle spread and reduce risk through surveys. However, the results also highlight differences in risk reduction among the eradication programs associated with differences in beetle dispersal among infestations and the size of the infested landscape, highlighting the importance of applying local information to structure eradication programs. The Asian Longhorned Beetle Hazard Management and Monitoring Tool provides a quantitative repeatable approach to tracking changes in infestation risk using local beetle behavior and management efforts. In addition to this, the tool may provide a structure to optimize eradication efforts by allowing managers to estimate expected risk reduction based on proposed survey and host removal strategies.

Colonoscopy and Reduction of Colorectal Cancer Risk by Molecular Tumor Subtypes: A Population-Based Case-Control Study.

In previous studies, the protective effect of colonoscopy was generally stronger for distal colorectal cancer than for proximal colorectal cancer (CRC). This study aimed to investigate whether reduction of CRC risk through colonoscopy varies according to major tumor markers and pathways of CRC. This is a population-based case-control study from Germany, including 2,132 patients with a first diagnosis of CRC and information on major molecular tumor markers and 2,486 control participants without CRC. Detailed participant characteristics were collected by standardized questionnaires. Information on previous colonoscopy was derived from medical records. Polytomous logistic regression was used to calculate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the association between previous colonoscopy and subtypes of CRC. Overall, we observed strong risk reduction of CRC after colonoscopy that was weaker for microsatellite instable (MSI) than for non-MSI CRC (OR 0.70, 95% CI 0.50-0.97 vs OR 0.28, 95% CI 0.24-0.33), for CpG island methylator phenotype high CRC than for CpG island methylator phenotype low/negative CRC (OR 0.45, 95% CI 0.34-0.59 vs OR 0.29, 95% CI 0.25-0.34), for BRAF-mutated than for BRAF nonmutated CRC (OR 0.62, 95% CI 0.42-0.91 vs OR 0.30, 95% CI 0.25-0.35), for KRAS nonmutated than for KRAS-mutated CRC (OR 0.34, 95% CI 0.29-0.40 vs OR 0.26, 95% CI 0.20-0.32), and for CRC classified into the sessile serrated pathway than for CRC of the traditional pathway (OR 0.57, 95% CI 0.36-0.91 vs OR 0.30, 95% CI 0.25-0.37). After colonoscopy with the detection of adenomas or hyperplastic polyps, no risk reduction was found for sessile serrated pathway CRC, MSI, and BRAF-mutated subtypes. Our study extends the molecular understanding of existing differences in risk reduction of proximal and distal CRCs reported by previous studies and may imply important information for improving strategies for timely detection of relevant precursors.

Contemporary hormonal contraception and risk of endometrial cancer in women younger than age 50: A retrospective cohort study of Danish women

ObjectiveTo examine the association between contemporary hormonal contraceptives and endometrial cancer risk in women younger than age 50. Study designCohort study of women living in Denmark aged 15–49 years through 1995–2014. National registries provided information about hormonal contraception use, incident endometrial cancer and confounders. Ever, current or recent, and former users of any hormonal contraception were compared with non-users, using Poisson regression to calculate incidence rate ratios (RR) with 95% confidence intervals. Duration, time since last use, tumor-specific and product-specific analyses, and population prevented fraction, were calculated. ResultsDuring 21.1 million person-years, 549 incident endometrial cancers occurred, with ever users of any hormonal contraception having a reduced premenopausal endometrial cancer risk compared with non-users; RR 0.60 (95% Confidence Interval 0.49 to 0.73). A lower risk of endometrial cancer was seen in all current or recent users of any hormonal contraception; 0.65 (0.52 to 0.83) and combined contraceptives; 0.57 (0.43 to 0.75), but not progestin-only contraceptives; levonorgestrel intrauterine system, LNG-IUS; 0.97 (0.66 to 1.42); other progestin-only contraceptives; 0.61 (0.27 to 1.37). Increased RRs were found for current use of any hormonal, combined contraceptives or LNG-IUS of ≤one year, probably because of protopathic bias. Longer durations of use were associated with significant reductions that became stronger with longer use. Former users of any hormonal contraception continued to benefit from a reduced risk of endometrial cancer >10 years after stopping.There was little evidence of differences in risk reduction by the type of progestin in combined oral contraceptives.Current or recent use of any hormonal contraception was associated with an approximate halving of risk of the most common tumor type I carcinoma, and an increased risk of the rarer sarcoma.Overall the estimated absolute reduced risk of endometrial cancer in ever users of hormonal contraceptives was 1.4 per 100,000 person-years, or approximately one less endometrial cancer for every 71,400 women of reproductive age who used hormonal contraception for one year. Use of hormonal contraception was estimated to prevent 25% of endometrial cancers in this population. ConclusionsCurrently available combined hormonal contraceptives are still associated with enduring protection against endometrial cancer, particularly for type I carcinomas. ImplicationsWe report substantive evidence of the association between different types of contemporary hormonal contraception and endometrial cancer risk in a national cohort of young Danish women. Currently available combined hormonal contraceptives are still associated with enduring protection against endometrial cancer, particularly for type I carcinomas.

Implementation interventions in preventing surgical site infections in abdominal surgery: a systematic review

BackgroundSurgical site infections (SSIs) are highly prevalent in abdominal surgery despite evidence-based prevention measures. Since guidelines are not self-implementing and SSI-preventive compliance is often insufficient, implementation interventions have been developed to promote compliance. This systematic review aims to identify implementation interventions used in abdominal surgery to prevent SSIs and determine associations with SSI reductions.MethodsLiterature was searched in April 2018 (Medline/PubMed and Web of Science Core Collection). Implementation interventions were classified using the implementation subcategories of the EPOC Taxonomy (Cochrane Review Group Effective Practice and Organisation of Care, EPOC). Additionally, an effectiveness analysis was conducted on the association between the number of implementation interventions, specific compositions thereof, and absolute and relative SSI risk reductions.ResultsForty studies were included. Implementation interventions used most frequently (“top five”) were audit and feedback (80% of studies), organizational culture (70%), monitoring the performance of healthcare delivery (65%), reminders (53%), and educational meetings (45%). Twenty-nine studies (72.5%) used a multimodal strategy (≥3 interventions). An effectiveness analysis revealed significant absolute and relative SSI risk reductions. E.g., numerically, the largest absolute risk reduction of 10.8% pertained to thirteen studies using 3–5 interventions (p < .001); however, this was from a higher baseline rate than those with fewer or more interventions. The largest relative risk reduction was 52.4% for studies employing the top five interventions, compared to 43.1% for those not including these. Furthermore, neither the differences in risk reduction between studies with different numbers of implementation interventions (bundle size) nor between studies including the top five interventions (vs. not) were significant.ConclusionIn SSI prevention in abdominal surgery, mostly standard bundles of implementation interventions are applied. While an effectiveness analysis of differences in SSI risk reduction by number and type of interventions did not render conclusive results, use of standard interventions such as audit and feedback, organizational culture, monitoring, reminders, and education at least does not seem to represent preventive malpractice. Further research should determine implementation interventions, or bundles thereof, which are most effective in promoting compliance with SSI-preventive measures in abdominal surgery.

Glucocorticoid Therapy is Associated with a Lower Risk of Dementia.

Recent evidence indicates an important role for neuroinflammation in the pathological cascade of Alzheimer's disease (AD), and neuroinflammation is increasingly being recognized as a potential therapeutic target. To assess the impact of glucocorticoids on the risk of developing dementia. We used health insurance data of the largest German health insurer from 2004-2013 with a baseline sample of 176,485 persons aged 50 years and older to study the association of glucocorticoid treatment and incidence of dementia. Cox proportional-hazard models were calculated adjusting for sex, age, and comorbidities known to be major risk factors for dementia and were given as hazard ratios (HR) with 95% confidence intervals (CI). We further stratified glucocorticoid treatment by route of application and treatment duration. Of the 176,485 dementia-free persons, 19,938 were diagnosed with dementia by the end of 2013. The risk of suffering from dementia was significantly lower for glucocorticoid users compared to non-users (HR = 0.81, CI = 0.78-0.84). The lowest risk was found among users of inhaled glucocorticoid (HR = 0.65, CI = 0.57-0.75), followed by nasal (HR = 0.76, CI = 0.66-0.87), other (HR = 0.84, CI = 0.80-0.88), and oral users (HR = 0.83, CI = 0.78-0.88). We found no difference in risk reduction between long- and short-term-users. Longitudinal German health insurance data indicate that the use of glucocorticoids is associated with a lower risk of dementia. Prospective clinical trials will be necessary to determine whether glucocorticoids can have a positive impact on neuroinflammation and thus protect persons against dementia.

Abstract P456: Examining Framingham Coronary Heart Disease 10-year Risk Reduction in Individuals Treated With Lorcaserin, a Selective 5HT 2C Receptor Agonist for Weight Management

Introduction: Obesity contributes significantly to cardiovascular disease (CVD) risk and weight management is associated with CVD risk reduction. Lorcaserin, a selective 5HT 2C receptor agonist, is indicated as an adjunct to a reduced-calorie diet and increase physical activity for weight management in adults with obesity (BMI≥30) and overweight (BMI 27-29.9 and ≥1 weight-related comorbidity). This analysis used the Framingham 10-year CVD risk to examine the impact of lorcaserin treatment on CVD risk and risk reduction. Method: Pooled data from two randomized, double-blind studies (BLOOM &amp; BLOSSOM) investigating the efficacy of lorcaserin vs. placebo among non-diabetic patients with overweight or obesity, were used in this analysis. Framingham CVD risk was calculated for those whose lipid values were available at baseline and at one year. A Framingham CVD risk of &lt;5% was classified as low risk. Patients were stratified by cohort, lorcaserin (LOR) vs. placebo (PBO) and response at week 12 (≥5% weight loss vs. &lt; 5%) for calculating the 10-year CVD risk at one year. Logistic regression was used to adjust for baseline risk and determine if proportional differences in risk reduction were significant. Results: A total of 5,658 patients were evaluated, 51% treated with LOR. Among the LOR-treated patients, 43% achieved ≥5% weight loss at week 12 (compared to 19% treated with PBO). At one year, more patients in the LOR cohort had reduced CVD risk (from high to low risk, 21% vs. 15%, respectively). The regression analysis showed LOR-treated patients were 34% more likely to have low CVD risk (p&lt;0.001). Similarly, for patients who lost ≥5% baseline body weight at 12 weeks, more patients in the LOR cohort had reduced CVD risk (from high to low risk, 26% vs. 16% respectively) at one year. The regression showed LOR-treated patients were 23% more likely to have low CVD risk (p&lt;0.05). Conclusion: The analysis suggests that patients treated with LOR are more likely to have low CVD risk at one year than those treated with PBO. The effect is magnified if patients have ≥5% weight loss at 12 weeks.

Suicide Prevention in an Emergency Department Population

Suicide is a leading cause of deaths in the United States. Although the emergency department (ED) is an opportune setting for initiating suicide prevention efforts, ED-initiated suicide prevention interventions remain underdeveloped. To determine whether an ED-initiated intervention reduces subsequent suicidal behavior. This multicenter study of 8 EDs in the United States enrolled adults with a recent suicide attempt or ideation and was composed of 3 sequential phases: (1) a treatment as usual (TAU) phase from August 2010 to December 2011, (2) a universal screening (screening) phase from September 2011 to December 2012, and (3) a universal screening plus intervention (intervention) phase from July 2012 to November 2013. Screening consisted of universal suicide risk screening. The intervention phase consisted of universal screening plus an intervention, which included secondary suicide risk screening by the ED physician, discharge resources, and post-ED telephone calls focused on reducing suicide risk. The primary outcome was suicide attempts (nonfatal and fatal) over the 52-week follow-up period. The proportion and total number of attempts were analyzed. A total of 1376 participants were recruited, including 769 females (55.9%) with a median (interquartile range) age of 37 (26-47) years. A total of 288 participants (20.9%) made at least 1 suicide attempt, and there were 548 total suicide attempts among participants. There were no significant differences in risk reduction between the TAU and screening phases (23% vs 22%, respectively). However, compared with the TAU phase, patients in the intervention phase showed a 5% absolute reduction in suicide attempt risk (23% vs 18%), with a relative risk reduction of 20%. Participants in the intervention phase had 30% fewer total suicide attempts than participants in the TAU phase. Negative binomial regression analysis indicated that the participants in the intervention phase had significantly fewer total suicide attempts than participants in the TAU phase (incidence rate ratio, 0.72; 95% CI, 0.52-1.00; P = .05) but no differences between the TAU and screening phases (incidence rate ratio, 1.00; 95% CI, 0.71-1.41; P = .99). Among at-risk patients in the ED, a combination of brief interventions administered both during and after the ED visit decreased post-ED suicidal behavior.

The effect of statin therapy on heart failure events: a collaborative meta-analysis of unpublished data from major randomized trials.

AimsThe effect of statins on risk of heart failure (HF) hospitalization and HF death remains uncertain. We aimed to establish whether statins reduce major HF events.Methods and resultsWe searched Medline, EMBASE, and the Cochrane Central Register of Controlled Trials for randomized controlled endpoint statin trials from 1994 to 2014. Collaborating trialists provided unpublished data from adverse event reports. We included primary- and secondary-prevention statin trials with >1000 participants followed for >1 year. Outcomes consisted of first non-fatal HF hospitalization, HF death and a composite of first non-fatal HF hospitalization or HF death. HF events occurring <30 days after within-trial myocardial infarction (MI) were excluded. We calculated risk ratios (RR) with fixed-effects meta-analyses. In up to 17 trials with 132 538 participants conducted over 4.3 [weighted standard deviation (SD) 1.4] years, statin therapy reduced LDL-cholesterol by 0.97 mmol/L (weighted SD 0.38 mmol/L). Statins reduced the numbers of patients experiencing non-fatal HF hospitalization (1344/66 238 vs. 1498/66 330; RR 0.90, 95% confidence interval, CI 0.84–0.97) and the composite HF outcome (1234/57 734 vs. 1344/57 836; RR 0.92, 95% CI 0.85–0.99) but not HF death (213/57 734 vs. 220/57 836; RR 0.97, 95% CI 0.80–1.17). The effect of statins on first non-fatal HF hospitalization was similar whether this was preceded by MI (RR 0.87, 95% CI 0.68–1.11) or not (RR 0.91, 95% CI 0.84–0.98).ConclusionIn primary- and secondary-prevention trials, statins modestly reduced the risks of non-fatal HF hospitalization and a composite of non-fatal HF hospitalization and HF death with no demonstrable difference in risk reduction between those who suffered an MI or not.

Further Exploration Of Global Asset GMVPs: Does Risk Reduction Benefit From Weekly Data?

The paper studies the differences in risk reduction among global minimum variance portfolios (GMVPs) derived from the optimization of weekly and monthly return. This research follows the analysis of Zibri and Kukeli (2014) regarding differences in performance which is measured for different revision frequencies and transaction costs. The data used are weekly/monthly returns for stock, bond, gold, oil indices for the period 1996-2013. If more frequently rebalancing is applied, most restrictive weekly GMVPs reduce risk more than returns vis--vis monthly GMVPs.

DNAPL Source Depletion: 2. Attainable Goals and Cost-Benefit Analyses

It is difficult to quantify the range in source strength reduction (MdR) that may be attainable from in situ remediation of a dense nonaqueous-phase liquid (DNAPL) site given that available studies typically report only the median MdR without providing insights into site complexity, which is often a governing factor. An empirical study of the performance of in situ remediation at a wide range of DNAPL-contaminated sites determined MdRs for in situ bioremediation (EISB), in situ chemical oxidation (ISCO), and thermal treatment remedies. Median MdR, geometric mean MdR, and lower/upper 95 percent confidence interval for the mean were: 49x, 105x, 20x/556x, respectively, for EISB; 9x, 21x, and 4x/110x for ISCO; and 19x, 31x, and 6x/150x for thermal treatment. Lower MdR values were determined for large, complex sites and for sites with DNAPL pool-dominated source zones. A feasibility analysis of partial DNAPL depletion is described for a pool-dominated source zone. Back-diffusion from low-hydraulic conductivity units within a pool-dominated source zone is shown to potentially sustain a secondary source for more than 1,000 years, indicating that aggressive source treatment may not reduce the remediation timeframe. Estimated plume response demonstrates there may be no reduction in cost associated with aggressive treatment, and little difference in risk reduction associated with the various alternatives. Monitored natural attenuation (MNA) for the source zone is shown to be a reasonable alternative for the pool-dominated source zone considered in this example. It is demonstrated that pool-dominated source zones with a large range in initial DNAPL mass (250 to 1,500 kg) may correspond to a narrow range in source strength (20 to 30 kg/year). This demonstrates that measured source strength is nonunique with respect to DNAPL mass in the subsurface and, thus, source strength should not be used as the sole basis for predicting how much DNAPL mass remains or must be removed to achieve a target goal. If aggressive source zone treatment is to be implemented due to regulatory requirements, strategic pump-and-treat is shown to be most cost effective. These remedial decisions are shown to be insensitive to a range of possible DNAPL pool conditions. At sites with an existing pump-and-treat system, a significant increase in mass removal and source strength reduction may be achieved for a low incremental cost by strategic placement of extraction wells and pumping rate selection. © 2014 Wiley Periodicals, Inc.

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Wang et al. summarized published reports and reached a result to support a potential negative association between thiazolidinediones (TZD) therapy and risk of liver cancer among type 2 diabetes patients. Evidence suggests that nonalcoholic fatty liver disease (NAFLD) is an independent risk factor for hepatocellular carcinoma (HCC). Several clinical trials demonstrate that TZD therapy may lead to improvements in certain metabolic and histological parameters in patients with NAFLD.1 However, the long-term RECORD and PROactive trials failed to find any difference in liver cancer occurrence between either rosiglitazone or pioglitazone and the active comparison group, probably because patients with chronic liver disease were excluded from the trials. Southeast Asia, including China, Taiwan, and Hong Kong, is the endemic area for chronic viral hepatitis. Our case-control study2 and Lai et al.'s cohort study,3 both using Taiwan's National Health Insurance Research Database, demonstrated that the use of TZD was associated with a reduced risk for HCC. There has been a concern that several methodological limitations, in particuluar, the inability to control for important clinical and behavioral factors, might affect the validity of observational studies that were based on large healthcare claims databases. In a recently published report, Yang et al. analyzed the Hong Kong Diabetic Registry and found that TZD was associated with lower overall cancer risk in a dose-response manner after controlling for potential confounding factors.4 However, the small number of TZD users did not allow a further exploration of the association between TZD use and site-specific cancers. Although some evidence suggests a potentially beneficial role of TZD against liver cancer, many questions need to be answered. For patients with NAFLD, does TZD therapy that leads to decrease in aminotransferace, reduction of steatosis, hepatocyte ballooning, or fibrosis result in decreased HCC risk? Among high-risk patients with chronic viral hepatitis B or C, does TZD therapy improve liver pathology and further reduce liver cancer risk? What is the potential role of TZD along with antiviral therapy? Is there any possible effect modification by viral genotypes?5 Is there any difference in risk reduction between rosiglitazone and pioglitazone? Are there any clinical, metabolic, or pathological factors that can predict response? We agreed with the researchers that all these questions have to be answered by well-designed studies with meticulously collected information on metabolic, biochemical, virological, and histological parameters. Randomized, controlled trials with intermediate outcomes may provide more solid evidence in support of the potential beneficial effects associated with TZD. Chia-HsuinChang M.D., D.Sc. Jou-Wei Lin M.D., M.P.H., Ph.D. Mei-Shu Lai M.D., Ph.D. Lee-Ming Chuang M.D., Ph.D. Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan Cardiovascular Center, National Taiwan University Hospital Yun-Lin Branch, Dou-Liou City, Taiwan Institute of Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

PC-FACS

PC-FACS

Abstract P168: Clinical Benefit of Reduction in LDL and Triglycerides: Meta-Analyses of Major Coronary Events

Objective: The primary objective of the analysis was to characterize the multivariate relationship between changes in LDL-C, HDL-C and triglycerides (TG) and risk for major coronary events after treatment with statins, fibrates or niacin. Methods: Randomized controlled trials that compared statin, fibrate or niacin treatment with placebo, usual care, or active control and that reported on major coronary events were identified by a literature search, prior meta-analyses and review articles. The dependency of the odds-ratio between active and control arm on the differences in on-treatment LDL-C, HDL-C and TG was determined using a meta-regression analysis. Differences in the risk reduction per unit change in lipid values between drug classes (fibrates, statins and niacin) and drugs within a class were evaluated. Differences in risk reduction per unit change in lipid values for certain patient groups such as diabetes, males, elderly, prior CHD were also evaluated. Results: A total of 70 trials were identified and included in the meta-analysis. The meta-analysis found a significant contribution of lowering TG on top of reducing LDL-C to the risk reduction for a major coronary event after treatment with statins, fibrates or niacin (p&lt;0.001). The risk reduction for major coronary events was estimated to be 18.5% [14.1 to 22.7%] for every 1 mmol/L (38.7 mg/dL) reduction in LDL-C and 27.5% [15.7 to 37.7%] for every 1 mmol/L (88.6 mg/dL) reduction in TG. The reduction in TG was found to explain most (84%) of the risk reduction for treatment with fibrates. For statins, the reduction in LDL-C was found to explain most (71%) of their benefit, but the reduction in TG was found to provide a statistically and clinically significant contribution to their overall risk reduction. The risk reduction per unit change in LDL-C and TG was not dependent on age, gender, diabetes and prior CHD and was not different between fibrates and statins. Conclusions: A significant additional risk reduction is expected by providing a reduction in TG on top of LDL-C changes. The independent effect of TG and LDL-C lowering supports the role for treatment combinations such as statins and fibrates that impact LDL-C and TG differentially.

Reconciling the Evidence on Serum Homocysteine and Ischaemic Heart Disease: A Meta-Analysis

BackgroundResults from genetic epidemiological studies suggest that raised serum homocysteine is a cause of ischaemic heart disease, but the results of randomised trials suggest otherwise. We aimed to update meta-analyses on each type of study using the latest published data and test a hypothesis based on antiplatelet therapy use in the trials to explain the discrepancy.Methods and FindingsMeta-analyses of ischaemic heart disease using (i) 75 studies in which the prevalence of a mutation (CT) in the MTHFR gene (which increases homocysteine) was determined in cases (22,068) and controls (23,618), and (ii) 14 randomised trials (39,597 participants) of homocysteine lowering and ischaemic heart disease events. The summary estimates from the two analyses were compared. Meta-analysis of the MTHFR studies showed a statistically significantly increased risk of ischaemic heart disease in TT compared with CC homozygotes; odds ratio 1.16 (1.04 to 1.29) for a 1.9 µmol/L homocysteine difference (TT minus CC). Meta-analysis of randomised trials showed no significant reduction in IHD risk from folic acid; relative risk 1.00 (0.93 to 1.08), despite a reduction in homocysteine of 3.3 µmol/L. There was a statistically significant difference in risk reduction between the 5 trials with the lowest prevalence of antiplatelet therapy (60% on average, usually aspirin), RR 0.93 (0.84 to 1.05) and the 5 trials with the highest prevalence (91% on average), RR 1.09 (1.00 to 1.19), p = 0.037 for the difference.ConclusionDiscordant results from MTHFR studies and randomised trials could be explained by aspirin reducing or negating the anti-platelet effect of lowering homocysteine. On this basis, folic acid would have a role in the primary prevention of ischaemic heart disease, when aspirin is not taken routinely, but not in secondary prevention, when it is routine.

Optimal management of hypertension in elderly patients.

Hypertension is a common and important modifiable risk factor for cardiovascular and kidney diseases. The prevalence of hypertension, particularly isolated systolic hypertension, increases with advancing age, and this is partly due to the age-related changes in the arterial tree, leading to an increase in arterial stiffness. Therapeutic lifestyle changes, such as reduced dietary sodium intake, weight loss, regular aerobic activity, and moderation of alcohol consumption, have been shown to benefit elderly patients with hypertension. Lowering blood pressure (BP) using pharmacological agents reduces the risk for cardiovascular morbidity and mortality, with no difference in risk reduction in elderly patients compared to younger hypertensives. Guidelines recommend a BP goal of <140/90 in hypertensive patients regardless of age and <130/80 in patients with concomitant diabetes or kidney disease, and lowering the BP further has not been shown to confer any additional benefit. Moreover, the choice of antihypertensive does not seem to be as important as the degree of BP lowering. Special considerations in the treatment of elderly hypertensive patients include cognitive impairment, dementia, orthostatic hypotension, and polypharmacy.

Reamed and unreamed intramedullary nailing for the treatment of open and closed tibial fractures: a subgroup analysis of randomised trials

The choice between reamed and unreamed intramedullary nailing for the treatment of open and closed tibial fractures is an ongoing controversy. We carried out a comprehensive search strategy. Six eligible randomised controlled trials were included. Three reviewers independently assessed methodological quality and extracted outcome data. Analyses were performed using Review Manager 5.0. The results showed lower risks of tibial fracture nonunion and implant failures with reamed nails compared to unreamed nails in closed tibial fractures [relative risk (RR): 0.41, 95% confidence interval (CI): 0.21-0.89, P = 0.008 for nonunion and RR: 0.35, 95% CI: 0.22-0.56, P < 0.0001 for implant failures], but no statistical differences in risk reduction of malunion, compartment syndrome, embolism and infection. Our results suggested no statistical differences in risk reduction of all the complications evaluated between reamed and unreamed nails in open tibial fractures. In conclusion, our study recommended reamed nails for the treatment of closed tibial fractures. But the choice for open tibial fractures remains uncertain.

Statins and cognitive function

Breteler and colleagues1 have provided us with data indicating a reduction in the risk of incident Alzheimer’s disease (AD) with elective statin use in the largest cohort investigation to date...

Cardiovascular Risk After Bariatric Surgery for Obesity

Obese patients have an increased prevalence of cardiovascular (CV) risk factors, which improve with bariatric surgery, but whether bariatric surgery reduces long-term CV events remains ill defined. A systematic review of published research was conducted, and CV risk models were applied in a validation cohort previously published. A standardized MEDLINE search using terms associated with obesity, bariatric surgery, and CV risk factors identified 6 test studies. The validation cohort consisted of a population-based, historical cohort of 197 patients who underwent Roux-en-Y gastric bypass and 163 control patients, identified through the Rochester Epidemiology Project. Framingham and Prospective Cardiovascular Munster Heart Study (PROCAM) risk scores were applied to calculate 10-year CV risk. In the validation cohort, absolute 10-year Framingham risk score for CV events was lower at follow-up in the bariatric surgery group (7.0% to 3.5%, p <0.001) compared with controls (7.1% to 6.5%, p = 0.13), with an intergroup absolute difference in risk reduction of 3% (p <0.001). PROCAM risk in the bariatric surgery group decreased from 4.1% to 2.0% (p <0.001), whereas the control group exhibited only a modest decrease (4.4% to 3.8%, p = 0.08). Using mean data from the validation study, the trend and directionality in risk was similar in the Roux-en-Y group. The test studies confirmed the directionality of CV risk, with estimated relative risk reductions for bariatric surgery patients ranging from 18% to 79% using the Framingham risk score compared with 8% to 62% using the PROCAM risk score. In conclusion, bariatric surgery predicts long-term decreases in CV risk in obese patients.