Catheter ablation for ventricular tachycardia (VT) in patients with ischemic heart disease: a systematic review and a meta-analysis of randomized controlled trials



Patients with ischemic heart disease may have implantable cardioverter defibrillators (ICDs) implanted for primary or secondary prevention of sudden cardiac death. Although ICD shocks can be life saving, in some patients, they have been associated with increased mortality and/or morbidity. Several studies have suggested that catheter ablation may be superior to non-ablative strategies at preventing ICD shocks delivered for ventricular arrhythmias; however, this is still controversial.


We performed a meta-analysis of randomized controlled trials (RCTs) comparing catheter ablation with non-ablative strategies in treatment of ventricular tachycardia (VT) in patients with ischemic heart disease and an ICD. The primary endpoints of interest were recurrent episodes of VT and death. We used a binary random effects method to calculate the cumulative odds ratios (OR) for recurrent VT and deaths.


Of a total of 643 potential citations, our search yielded three citations that met our inclusion and exclusion criteria. In the three trials, a total of 262 patients were randomized to ablation (n = 129) or non-ablative interventions (beta-blockers ± use of antiarrhythmics) (n = 133) group. The cumulative OR for recurrent VT was 0.471 (95 % confidence interval (CI) = 0.176–1.257) for catheter ablation compared with non-ablative strategies, and for death, it was 0.766 (95 % CI = 0.351–1.674). Excluding one study for being appreciably smaller than the other two, the OR for recurrent VT was 0.298 (95 % CI = 0.164–0.543).


In this meta-analysis, the rate of recurrent VT was lower with VT catheter ablation compared with non-ablative strategies. There was not a significant difference in rate of death among patients receiving catheter ablation versus non-ablative strategies for management of VT. Given the lack of adequately powered RCTs comparing ablation versus medical management of VT in patients with ischemic heart disease and an ICD, larger studies with longer follow-up are needed.


Colloids versus crystalloids for fluid resuscitation in critically ill patients.

Critically ill patients with trauma, burns, surgery or sepsis are often given intravenous fluids to expand intravascular volume. When it comes to selecting the resuscitation fluid, one of the choices is between using a colloid or a crystalloid solution. This choice has considerable cost implications, because volume replacement with colloids is much more expensive than with crystalloids. Clinical studies have shown that colloids and crystalloids have different effects on a range of physiological parameters. Because of these differences, all-cause mortality is arguably the most clinically relevant outcome measure for randomised trials comparing the two fluid types.

This review, which was updated for the sixth time in February 2013, assessed the effects on mortality of using colloids compared to crystalloids, during fluid resuscitation in critically ill patients. A systematic search was conducted for any controlled trial in which participants were assigned to treatment on the basis of random allocation. The interventions considered were colloids (dextran 70, hydroxyethyl starches, modified gelatins, albumin or plasma protein fraction) compared to crystalloid (isotonic or hypertonic) for fluid replacement. Studies needed to include critically ill patients (excluding neonates and pregnant women) who required volume replacement. The authors excluded trials of fluids used for other purposes, such as trials of pre-loading in preparation for elective surgery, and trials in patients undergoing fluid loading before cardiopulmonary bypass. Trials of total parenteral nutrition with or without albumin were also excluded, as were randomised cross-over trials.

A total of 78 eligible trials were identified, with mortality data available from 70 of these. The analyses were divided up on the basis of the types of intervention. Considering the basic comparison of colloids versus crystalloids, the largest number of randomized patients was in the studies of albumin or plasma protein fraction, with 24 trials that reported data on mortality (9920 patients). The pooled risk ratio (RR) from these trials was 1.01 (95% confidence interval (CI) 0.93 to 1.10). 25 trials compared hydroxyethyl starch with crystalloids (9147 patients), finding a pooled RR of 1.10 (95% CI 1.02 to 1.19). In the 11 trials of modified gelatin versus crystalloid, with 506 patients, the pooled RR was 0.91 (95% CI 0.49 to 1.72) and, for the 9 trials comparing dextran with a crystalloid (834 patients), the meta-analysis produced a RR of 1.24 (95% CI 0.94 to 1.65).

In other comparisons in the review, 9 trials compared dextran in hypertonic crystalloid with isotonic crystalloid (1985 patients), generating a pooled RR for mortality of 0.91 (95% CI 0.71 to 1.06). While there were three trials of colloids in isotonic crystalloid versus hypertonic crystalloid. In two of these trials, where the colloid was either gelatin or starch, there were no deaths in either group. In the third trial (38 patients), there were three deaths in the treatment group and none in the control group, giving a RR of 7.00 (95% CI 0.39 to 126.93).

In their summary, the authors of this updated Cochrane Review highlight that there is no evidence from randomised trials that resuscitation using colloids compared with crystalloids reduces the risk of death in patients with trauma, burns or following surgery. Their meta-analyses provide a precise estimate of hydroxyethyl starch effect on mortality, since it includes many thousands of patients and the number of deaths is large. Furthermore, the two studies that contribute 80% of the weight in the meta-analysis were of high methodological quality with a low risk of bias. The pooled relative risk of death (1.10 [95% CI 1.02 to 1.19]) suggests an increase in deaths in the colloids group, and makes it highly unlikely that there is a mortality reduction with these interventions. Therefore, since colloid use is not associated with improved survival and colloids are considerably more expensive than crystalloids, they conclude that it is difficult to see how their continued use in clinical practice can be justified.

More Than Just Reassurance on Tiotropium Safety.

Since its registration in 2002, a dry-powder formulation of tiotropium delivered by a HandiHaler inhalation device has consistently been recommended in clinical-practice guidelines as first-line maintenance bronchodilator therapy for chronic obstructive pulmonary disease (COPD). This recommendation is based on the efficacy of tiotropium in improving lung function, exercise capacity, and quality of life and in reducing moderate and severe COPD exacerbations.

The safety reputation of tiotropium as delivered by dry-powder inhalation remained relatively unblemished until its successor, tiotropium delivered by a soft-mist Respimat inhaler, underwent clinical trials. Despite the clear efficacy of the Respimat formulation, post hoc pooled safety analyses showed an increased rate of death from any cause in patients treated with the Respimat inhaler at a dose of 5 μg of tiotropium, as compared with placebo, an effect that was particularly evident in patients with a history of cardiac arrhythmias.1 All of a sudden, the previous hints at the possibility of cardiovascular risk for ipratropium and tiotropium held more water and needed to be addressed, especially given the widespread use of this drug, the increasing global prevalence of COPD, the guideline recommendations for tiotropium as a first-line COPD treatment, and the high burden of coexisting cardiac conditions and deaths in the COPD population.

Multiple meta-analyses and observational database studies did not resolve the issue, and regulators issued warnings.2 In a systematic review of pooled data from 17 trials (enrolling a total of 13,645 participants), patients with COPD who received inhaled anticholinergic medications had higher rates of myocardial infarction, stroke, and death from cardiovascular causes or a composite of all three outcomes than those receiving placebo or an active control, with a relative risk of 1.60 (95% confidence interval [CI], 1.22 to 2.10; P<0.001) for cardiovascular events and 1.29 (95% CI, 1.00 to 1.65; P=0.05) for death from any cause.3 However, several other meta-analyses showed no evidence of increased rates of cardiovascular events or death.4,5 Most important, data from the Understanding Potential Long-Term Impacts on Function with Tiotropium (UPLIFT) trial6 were consistent with a reduction in all-cause mortality in patients with COPD who were receiving tiotropium, as compared with those receiving placebo, during a 4-year period, with a protective effect for cardiac mortality. A subsequent meta-analysis of 30 trials including UPLIFT (enrolling a total of 19,545 participants) showed that tiotropium was associated with reduced rates of death from any cause and from cardiac causes and of cardiovascular events.5However, the soft-mist Respimat inhaler remained under a cloud, with a systematic review reporting a 50% increased risk of death in 2011.1 Although a Cochrane review of 22 studies (enrolling a total of 23,309 participants) did not show an increased risk of death from any cause associated with dry-powder tiotropium HandiHaler, it showed significantly more deaths associated with the soft-mist Respimat inhaler (Peto odds ratio, 1.47; 95% CI, 1.04 to 2.08), with placebo used as the control in the two comparisons.7

Large randomized, controlled trials are usually designed and powered to meet statistical certainty for efficacy end points that have clinical significance for clinicians, patients, or regulators. But when efficacy has been established and safety is then questioned, it is sadly not the rule that rigorous, well-powered studies are conducted to address these concerns. Most studies are grossly underpowered for safety outcomes, and adverse events are listed with small numbers to which only an eyeball test can be applied. The reporting of “no difference” between adverse events in an intervention group and those in a control group is hardly ever questioned, even though it rarely has statistical validity.

In the Tiotropium Safety and Performance in Respimat (TIOSPIR) study,8 Wise et al. turn this tradition on its head by seriously addressing the widely expressed concern about the safety of tiotropium Respimat. In this large clinical trial, now reported in the Journal, involving 17,135 patients with COPD for a median duration of 835 days, the investigators compared the safety and efficacy of once-daily tiotropium doses of 2.5 μg and 5 μg delivered by Respimat with a once-daily dose of 18 μg of tiotropium delivered by HandiHaler. Primary end points were the rate of death (noninferiority study for both doses of Respimat vs. HandiHaler) and the rate of the first COPD exacerbation (superiority study for Respimat 5 μg vs. HandiHaler). There was no significant difference among the three study groups with respect to death (hazard ratio for Respimat 5 μg vs. Handihaler, 0.96; 95% CI, 0.84 to 1.09; hazard ratio for Respimat 2.5 μg vs. Handihaler, 1.0; 95% CI, 0.87 to 1.14) or the first exacerbation (hazard ratio for Respimat 5 μg vs. HandiHaler, 0.98; 95% CI, 0.93 to 1.03). Patients with stable cardiac disease were included in the study, and there was no significant difference in mortality for those with a history of arrhythmia. The incidences of major cardiovascular adverse events were similar in the three study groups.

These results address several previous criticisms leveled against randomized, controlled trials and meta-analyses that did not identify an increased risk of death (or that showed a risk reduction) associated with tiotropium. A major concern was the possibility that the failure to identify a risk of death in some meta-analyses was due to the exclusion of patients with a cardiac history, especially arrhythmia or recent myocardial infarction, or those with other serious coexisting illnesses who might be at risk because of participation in the trial. In the TIOSPIR study, the clinical characteristics, coexisting illnesses, and coprescribed medications of the recruited patients suggest they do represent typical patients with symptomatic COPD, and the rate of follow-up was 99.7%. However, it is important to note that the absence of a placebo group in this study has implications for its interpretation and that it cannot be concluded from these results that tiotropium reduces mortality in patients with COPD.

The rigor, careful conduct, scrupulous follow-up of patients, and use of clinically appropriate entry criteria in this study will reassure many clinicians who may have had concerns about the narrow focus of some COPD trials. The global recruitment, fast completion, and clear outcomes of the trial should also encourage all those who fear that real-world studies enrolling patients who truly reflect typically heterogeneous populations and phenotypes will produce messy, uninterpretable results. This study clears the air regarding the safety of tiotropium delivered by Respimat and at the same time establishes a high standard for clinical trials involving patients with COPD, particularly studies that focus on patient safety.


Source: NEJM



The Relation Between Intelligence and Religiosity.

A Meta-Analysis and Some Proposed Explanations

A meta-analysis of 63 studies showed a significant negative association between intelligence and religiosity. The association was stronger for college students and the general population than for participants younger than college age; it was also stronger for religious beliefs than religious behavior. For college students and the general population, means of weighted and unweighted correlations between intelligence and the strength of religious beliefs ranged from −.20 to −.25 (mean r = −.24). Three possible interpretations were discussed. First, intelligent people are less likely to conform and, thus, are more likely to resist religious dogma. Second, intelligent people tend to adopt an analytic (as opposed to intuitive) thinking style, which has been shown to undermine religious beliefs. Third, several functions of religiosity, including compensatory control, self-regulation, self-enhancement, and secure attachment, are also conferred by intelligence. Intelligent people may therefore have less need for religious beliefs and practices.

  • Source: SAGE


Weighing the Evidence: Studies Collide over How Aging Impacts Obesity Risk.



A meta-analysis found that carrying extra pounds becomes less risky with age, but two new studies dispute the “obesity paradox

Few phenomena have created as divisive a rift recently among health professionals as the so-called “obesity paradox,” the repeated finding that obese people with certain health conditions live longer than slender people with the same ailments. And when a January meta-analysis involving nearly three million research subjects suggested that overweight people in the general population also live longer than their slimmer counterparts, the head of Harvard University’s nutrition department, Walter Willett, called the work “a pile of rubbish.” A few new studies suggest that these paradoxes may largely be artifacts of flawed research designs, but some experts disagree, accusing the new studies of being inaccurate. Among the biggest questions raised by this new research is the impact of age: whether obesity becomes more or less deadly as people get older and why.

weighing-the-evidence-studies-collide-over-obesity-risk_1 (1)

The January meta-analysis, led by U.S. Centers for Disease Control and Prevention senior scientist Katherine Flegal, pooled data from 97 studies of the general global population and reported that, in sum, overweight individuals—those with a body mass index of 25 to 29.9—were 6 percent less likely to die over various short time periods than people of normal weight (with a BMI 18.5 to 24.9) were. For people over the age of 65, however, being overweight conferred a 10 percent survival advantage. Flegals’ findings also suggest that obesity, which has always been considered a major health risk, is not always dangerous and that it becomes less so with age: Adults with grade 1 obesity (BMIs of 30 to 34.9), she found, were no more likely to die than were normal weight adults; for grade 2 obesity (BMI of 35 to 39.9), the increased death risk for adults of all ages was 29 percent, but restricting the analysis to adults over the age of 65, the increased death risk associated with grade 2 obesity was not statistically significant.. The older a person is, the analysis seemed to say, the safer extra pounds become.

Two new studies, however, challenge the notion that extra weight, whether a little or a lot, can be safe. They also suggest that age is closely related to weight-related health risk and that added pounds could be more, not less, dangerous in old age than in youth. In a March 2013 analysis published in the American Journal of Epidemiologyand based on U.S. National Health Interview Survey data, Ryan Masters, a Robert Wood Johnson Foundation Health and Society Scholar at Columbia University, and his colleagues reported that grade 1 obesity (a BMI of 30 to 34.9) increases the death risk 45- to 54-year-old men by 10 percent but that among 75- to 84-year-olds, the increased death risk is 59 percent. (For women the percentages were even larger—15 percent and 72 percent, respectively.) Mortality risks for being overweight, they found, increased with age too. In a follow-up study published online last week in theAmerican Journal of Public Health, Masters and his colleagues concluded that, overall, obesity was responsible for 18 percent of all deaths among 40- to 85-year-olds between 1986 and 2006—a figure that is more than four times higher than some previous estimates.

How can two groups looking at similar populations come to such different conclusions? In part, the discrepancy stems from how the researchers consider age. Although the CDC researchers separated out the impacts of obesity and overweight at younger and older ages, they didn’t account for potential age-related influences that, according to Masters, strongly affect the relationship between weight and mortality. One such factor is selection bias. When scientists invite individuals to participate in survey-based studies, those who sign up are usually the healthy ones. This effect is likely to be magnified in elderly populations and particularly in obese elderly populations, Masters says. The small percentage of obese elderly people who participate in studies are likely to be in much better condition than the ones who don’t, which can make it seem as if obesity is less dangerous in old age than it really is. When Masters and his colleagues controlled for this effect using statistical methods and then calculated the mortality risks associated with obesity in the U.S. National Health Interview Survey data, they found that obesity was far deadlier in old age than the CDC meta-analysis had suggested it to be.

Masters and his colleagues accounted for two other potentially important age-related effects as well. One is that people born in 1950 tend to live to older ages than people born in 1930. And the latter group tends to live to older ages than people born in 1910, because those born later spend more of their lives reaping the benefits of public health interventions such as sanitation, refrigeration and modern medicine. The second is that  people born later also spend more of their lives exposed to relatively new environmental influences that are thought to drive the obesity epidemic—ubiquitous processed foods and sugar-sweetened beverages, hormone-disrupting chemicals, and sedentary behaviors. “People who are born later get a greater duration of exposure to all those obesity-inducing environmental changes,” Masters says, and “this cohort-based exposure is the key component to trying to understand not only your likelihood of being obese in America, but the chance for obesity to negatively impact your health and thus impact your mortality risk.” Although grade 1 obesity accounted for 3.4 percent of deaths at age 66 among white men born from 1915 to 1919, it accounted for 5.8 percent of deaths at age 66 for white men born 20 years later, Masters found. Ultimately, according to the new studies, the research suggesting obesity to be “safe” in old age didn’t account for the fact that the seniors being followed had not been obese for very long; future seniors who gain significant weight at a younger age and keep it on will have a much greater mortality risk.

Willett—the Harvard nutrition professor who strongly opposes the notion of anobesity paradox—largely agrees with the new findings and the idea that birth period shapes obesity-related mortality risk. “This is likely to become even more important as the current cohort of adolescents and young adults gets older, as it is true that the adverse effects of overweight are cumulative over a lifetime,” he says. Willett thinks, however, that there are many other spurious causes for the obesity paradox, too, including the fact that as people get sicker, they often lose weight, a trend that associates slimness with poor health even though in these cases slimness hasn’tcaused poor health. (Masters attempted to control for this so-called “reverse causation” by excluding people from his analysis who had a BMI under 18.5.) Other researchers try to account for this effect by excluding sick people from their analyses: In a study published online in August, for instance, Harvard nutrition researcher Chandra Jackson and her colleagues analyzed data from the general U.S. population and found that mortality risk appeared to decrease with increasing BMI among people with diagnosed diabetes; when they excluded those with diabetes, excess weight increased death risk. “It is imperative to address the methodological concerns that could lead to misleading conclusions,” says Jackson, who agrees that the obesity paradox is likely specious and that birth period could have important confounding effects, too.

Others are not convinced by the new findings. Flegal, the lead author of the CDC meta-analysis, says she does not think that her findings were biased by cohort effects, in part because many of the studies included in her analysis did not pool mortality estimates from wildly different age groups. She also says there’s little evidence that her findings were affected by selection bias. Neil Mehta, a professor of global health at Emory University who also studies the impact of obesity on mortality, says that the statistical method used by Masters and his colleagues “is questionable,” in part because it does not properly separate certain interrelated variables. The new findings ultimately inflate the risks of obesity in old age because older people, he says, suffer from many health problems and tend to die of a variety of causes. Yet Mehta agrees that “obesity duration matters a lot to mortality—the longer you are obese the higher the risk of dying,” a notion that his research supports, too.

Eric Reither, a sociologist at Utah State University and a co-author of the new studies with Masters, notes that their research is not necessarily at odds with Flegal’s work. “They also find that obesity contributes to premature mortality,” he says. “I would say that we build upon their research.” And although the new studies do little to settle the overall obesity paradox controversy, they do suggest that the impact of weight may be importantly dependent on age. “When people talk about the effect of [being] overweight or obesity on mortality risk, they often think it exists in a vacuum—that to be overweight at age 20 is to be overweight at age 60 is to be overweight at age 75,” Masters says. Instead of simply focusing on how age might influence the impact of obesity, he explains, scientists should consider that obesity might fundamentally shape the way people age—even if, right now, there’s no consensus on how it does so or even the nature of its influence.

Perceived job insecurity as a risk factor for incident coronary heart disease: systematic review and meta-analysis.


Objective To determine the association between self reported job insecurity and incident coronary heart disease.

Design A meta-analysis combining individual level data from a collaborative consortium and published studies identified by a systematic review.

Data sources We obtained individual level data from 13 cohort studies participating in the Individual-Participant-Data Meta-analysis in Working Populations Consortium. Four published prospective cohort studies were identified by searches of Medline (to August 2012) and Embase databases (to October 2012), supplemented by manual searches.

Review methods Prospective cohort studies that reported risk estimates for clinically verified incident coronary heart disease by the level of self reported job insecurity. Two independent reviewers extracted published data. Summary estimates of association were obtained using random effects models.

Results The literature search yielded four cohort studies. Together with 13 cohort studies with individual participant data, the meta-analysis comprised up to 174 438 participants with a mean follow-up of 9.7 years and 1892 incident cases of coronary heart disease. Age adjusted relative risk of high versus low job insecurity was 1.32 (95% confidence interval 1.09 to 1.59). The relative risk of job insecurity adjusted for sociodemographic and risk factors was 1.19 (1.00 to 1.42). There was no evidence of significant differences in this association by sex, age (<50 v ≥50 years), national unemployment rate, welfare regime, or job insecurity measure.

Conclusions The modest association between perceived job insecurity and incident coronary heart disease is partly attributable to poorer socioeconomic circumstances and less favourable risk factor profiles among people with job insecurity.

Source: BMJ

Intake of fish and marine n-3 polyunsaturated fatty acids and risk of breast cancer: meta-analysis of data from 21 independent prospective cohort studies.


Objectives To investigate the association between intake of fish and n-3 polyunsaturated fatty acids (n-3 PUFA) and the risk of breast cancer and to evaluate the potential dose-response relation.

Design Meta-analysis and systematic review of prospective cohort studies.

Data sources PubMed and Embase up to December 2012 and references of retrieved relevant articles.

Eligibility criteria for selecting studies Prospective cohort studies with relative risk and 95% confidence intervals for breast cancer according to fish intake, n-3 PUFA intake, or tissue biomarkers.

Results Twenty six publications, including 20 905 cases of breast cancer and 883 585 participants from 21 independent prospective cohort studies were eligible. Eleven articles (13 323 breast cancer events and 687 770 participants) investigated fish intake, 17 articles investigated marine n-3 PUFA (16 178 breast cancer events and 527 392 participants), and 12 articles investigated alpha linolenic acid (14 284 breast cancer events and 405 592 participants). Marine n-3 PUFA was associated with 14% reduction of risk of breast cancer (relative risk for highest v lowest category 0.86 (95% confidence interval 0.78 to 0.94), I2=54), and the relative risk remained similar whether marine n-3 PUFA was measured as dietary intake (0.85, 0.76 to 0.96, I2=67%) or as tissue biomarkers (0.86, 0.71 to 1.03, I2=8%). Subgroup analyses also indicated that the inverse association between marine n-3 PUFA and risk was more evident in studies that did not adjust for body mass index (BMI) (0.74, 0.64 to 0.86, I2=0) than in studies that did adjust for BMI (0.90, 0.80 to 1.01, I2=63.2%). Dose-response analysis indicated that risk of breast cancer was reduced by 5% per 0.1g/day (0.95, 0.90 to 1.00, I2=52%) or 0.1% energy/day (0.95, 0.90 to 1.00, I2=79%) increment of dietary marine n-3 PUFA intake. No significant association was observed for fish intake or exposure to alpha linolenic acid.

Conclusions Higher consumption of dietary marine n-3 PUFA is associated with a lower risk of breast cancer. The associations of fish and alpha linolenic acid intake with risk warrant further investigation of prospective cohort studies. These findings could have public health implications with regard to prevention of breast cancer through dietary and lifestyle interventions.


In this meta-analysis dietary intake of marine n-3 polyunsaturated fatty acids (PUFA), but not alpha linolenic acid (ALA), was associated with a lower risk of breast cancer. Fish consumption was not associated with risk. Dose-response analyses indicated a 5% lower risk of breast cancer per 0.1g/day or 0.1% energy/day increment of dietary marine n-3 PUFA, but no significant trend for ALA or fish intake. To the best of our knowledge, this is the first time meta-analysis has systematically and quantitatively evaluated the association between intake of fish and n-3 PUFA and risk of breast cancer.

Source: BMJ

Selective Amygdalohippocampectomy vs. Anterior Temporal Lobectomy for Epilepsy

In a meta-analysis of nonrandomized studies, seizure-free outcome was greater after ATL than after SAH.


In the surgical treatment of intractable medial temporal lobe epilepsy (MTLE), an important unanswered question is whether seizure-free outcome is better with standard anterior temporal lobe resection (ATL) or with a more restrictive procedure, selective amygdalohippocampectomy (SAH). In theory, SAH might mitigate some neuropsychological deficits that are associated with ATL. However, seizure freedom also has important psychosocial benefits. To examine this question, researchers conducted an exhaustive systematic review and meta-analysis of published studies on seizure outcomes following either ATL or SAH. They identified 13 studies that compared the two procedures. Nearly all studies were from individual centers, and follow-up was carried out by clinic visits or telephone calls by investigators or unspecified individuals. Duration of outcome measures ranged from 1 year to a median of 10.9 years. Only three studies separated follow-up according to procedure type; in two, follow-up was an average of 14 to 26 months longer for ATL; in the third, follow-up was an average of 2 months longer for SAH. Other differences in study populations were not specified.

From 11 studies that provided dichotomous outcomes (Engel class I vs. Engel class II–IV), 583 participants had SAH and 620 had ATL. Seizure-free outcome was significantly greater with ATL at final follow-up (relative risk, 1.32; risk difference, 8%; number needed to treat, 13). Results were similar with a more conservative random effects model, in the subset of studies with standardized outcome duration, and among patients with only hippocampal sclerosis. Cumulative addition of studies to the meta-analysis demonstrated a stable RR estimate starting before the most recent three studies were added. Five studies providing data on surgical complications in 392 after ATL and 309 after SAH showed no significant difference.

Comment: This thorough meta-analysis exploited a sufficiently large number of cases, roughly balanced between anterior temporal lobe resection and selective amygdalohippocampectomy (SAH), to provide meaningful information regarding the difference in seizure-free outcomes. This study is particularly valuable because a randomized, controlled trial (RCT) — which the authors say is “justified” — is unlikely to be funded. And yet, an RCT is a compelling proposal if only to address the need for balance in each treatment arm of known variables that affect seizure outcome. Further, only an RCT can answer whether the central postulated benefit of SAH — reduced neuropsychological deficits — exists.


Source: Journal Watch Neurology



Diagnostic accuracy of conventional or age adjusted D-dimer cut-off values in older patients with suspected venous thromboembolism: systematic review and meta-analysis.


Objective To review the diagnostic accuracy of D-dimer testing in older patients (>50 years) with suspected venous thromboembolism, using conventional or age adjusted D-dimer cut-off values.

Design Systematic review and bivariate random effects meta-analysis.

Data sources We searched Medline and Embase for studies published before 21 June 2012 and we contacted the authors of primary studies.

Study selection Primary studies that enrolled older patients with suspected venous thromboembolism in whom D-dimer testing, using both conventional (500 µg/L) and age adjusted (age×10 µg/L) cut-off values, and reference testing were performed. For patients with a non-high clinical probability, 2×2 tables were reconstructed and stratified by age category and applied D-dimer cut-off level.

Results 13 cohorts including 12 497 patients with a non-high clinical probability were included in the meta-analysis. The specificity of the conventional cut-off value decreased with increasing age, from 57.6% (95% confidence interval 51.4% to 63.6%) in patients aged 51-60 years to 39.4% (33.5% to 45.6%) in those aged 61-70, 24.5% (20.0% to 29.7% in those aged 71-80, and 14.7% (11.3% to 18.6%) in those aged >80. Age adjusted cut-off values revealed higher specificities over all age categories: 62.3% (56.2% to 68.0%), 49.5% (43.2% to 55.8%), 44.2% (38.0% to 50.5%), and 35.2% (29.4% to 41.5%), respectively. Sensitivities of the age adjusted cut-off remained above 97% in all age categories.

Conclusions The application of age adjusted cut-off values for D-dimer tests substantially increases specificity without modifying sensitivity, thereby improving the clinical utility of D-dimer testing in patients aged 50 or more with a non-high clinical probability.


What is already known on this topic

  • A negative D-dimer test can rule out venous thromboembolism in patients with a non-high clinical probability
  • Since D-dimer levels increase with age, the proportion of false positive D-dimer test results for venous thromboembolism using conventional cut-off values (500 µg/L) increases in older patients and the specificity decreases
  • Age adjusted D-dimer cut-off values (age×10 µg/L) have therefore been introduced
  • This systematic review and meta-analysis established a poor specificity (around 15%) of D-dimer testing with the conventional cut-off value in the eldest patients (>80 years)
  • The application of the age adjusted cut-off value increased the specificity of the D-dimer test to 35% in the eldest patients, while hardly affecting the sensitivity
  • Use of age adjusted D-dimer cut-off values would result in imaging examinations being correctly avoided in 30-54% of older patients with a non-high clinical probability of venous thromboembolism.
  • Source: BMJ

What this study adds

Use of high potency statins and rates of admission for acute kidney injury: multicenter, retrospective observational analysis of administrative databases.


Objective To quantify an association between acute kidney injury and use of high potency statins versus low potency statins.

Design Retrospective observational analysis of administrative databases, using nine population based cohort studies and meta-analysis. We performed as treated analyses in each database with a nested case-control design. Rate ratios for different durations of current and past statin exposure to high potency or low potency statins were estimated using conditional logistic regression. Ratios were adjusted for confounding by high dimensional propensity scores. Meta-analytic methods estimated overall effects across participating sites.

Setting Seven Canadian provinces and two databases in the United Kingdom and the United States.

Participants 2 067 639 patients aged 40 years or older and newly treated with statins between 1 January 1997 and 30 April 2008. Each person hospitalized for acute kidney injury was matched with ten controls.

Intervention A dispensing event was new if no cholesterol lowering drug or niacin prescription was dispensed in the previous year. High potency statin treatment was defined as ≥10 mg rosuvastatin, ≥20 mg atorvastatin, and ≥40 mg simvastatin; all other statin treatments were defined as low potency. Statin potency groups were further divided into cohorts with or without chronic kidney disease.

Main outcome measure Relative hospitalization rates for acute kidney injury.

Results Of more than two million statin users (2 008 003 with non-chronic kidney disease; 59 636 with chronic kidney disease), patients with similar propensity scores were comparable on measured characteristics. Within 120 days of current treatment, there were 4691 hospitalizations for acute kidney injury in patients with non-chronic kidney injury, and 1896 hospitalizations in those with chronic kidney injury. In patients with non-chronic kidney disease, current users of high potency statins were 34% more likely to be hospitalized with acute kidney injury within 120 days after starting treatment (fixed effect rate ratio 1.34, 95% confidence interval 1.25 to 1.43). Users of high potency statins with chronic kidney disease did not have as large an increase in admission rate (1.10, 0.99 to 1.23). χ2 tests for heterogeneity confirmed that the observed association was robust across participating sites.

Conclusions Use of high potency statins is associated with an increased rate of diagnosis for acute kidney injury in hospital admissions compared with low potency statins. The effect seems to be strongest in the first 120 days after initiation of statin treatment.

source: BMJ