Zhen-Yu Tang

Fruit and vegetable intake and risk of type 2 diabetes mellitus: meta-analysis of prospective cohort studies

Objective To clarify and quantify the potential dose–response association between the intake of fruit and vegetables and risk of type 2 diabetes. Design Meta-analysis and systematic review of prospective cohort studies. Data source Studies published before February 2014 identified through electronic searches using PubMed and Embase. Eligibility criteria for selecting studies Prospective cohort studies with relative risks and 95% CIs for type 2 diabetes according to the intake of fruit, vegetables, or fruit and vegetables. Results A total of 10 articles including 13 comparisons with 24 013 cases of type 2 diabetes and 434 342 participants were included in the meta-analysis. Evidence of curve linear associations was seen between fruit and green leafy vegetables consumption and risk of type 2 diabetes (p=0.059 and p=0.036 for non-linearity, respectively). The summary relative risk of type 2 diabetes for an increase of 1 serving fruit consumed/day was 0.93 (95% CI 0.88 to 0.99) without heterogeneity among studies (p=0.477, I2=0%). For vegetables, the combined relative risk of type 2 diabetes for an increase of 1 serving consumed/day was 0.90 (95% CI 0.80 to 1.01) with moderate heterogeneity among studies (p=0.002, I2=66.5%). For green leafy vegetables, the summary relative risk of type 2 diabetes for an increase of 0.2 serving consumed/day was 0.87 (95% CI 0.81 to 0.93) without heterogeneity among studies (p=0.496, I2=0%). The combined estimates showed no significant benefits of increasing the consumption of fruit and vegetables combined. Conclusions Higher fruit or green leafy vegetables intake is associated with a significantly reduced risk of type 2 diabetes.

Hyperuricemia and risk of stroke: A systematic review and meta-analysis of prospective studies

INTRODUCTION Hyperuricemia may be associated with an increased risk of stroke, but to date results from prospective studies have been inconsistent. This study aimed to evaluate the association between hyperuricemia and risk of stroke incidence and mortality by performing a meta-analysis. MATERIALS AND METHODS Studies were identified by searching multiple electronic databases through July 13, 2013, and by reviewing reference lists of obtained articles. Prospective studies reported a multivariate-adjusted estimate, represented as relative risk (RRs) with 95% confidence intervals (CIs) for the association between hyperuricemia and risk of stroke incidence and mortality were eligible. A random-effects model was used to compute the pooled risk estimate. RESULTS A total of fourteen articles including results from 15 prospective studies with 22,571 cases of stroke and 1,042,358 participants were included in the meta-analysis. Overall, presence of hyperuricemia was associated with a significantly greater risk of both stroke incidence (RR, 1.22; 95% CI, 1.02-1.46) and mortality (RR, 1.33; 95% CI, 1.24-1.43). In addition, the pooled estimate of multivariate RRs of stroke incidence and mortality were 1.08 (95% CI: 0.85-1.38); 1.26 (95% CI: 1.14-1.40) among men and 1.25 (95% CI: 1.04-1.46); 1.41 (95% CI: 1.31-1.52) among women respectively. CONCLUSIONS Results from this meta-analysis indicate that hyperuricemia may modestly increase the risks of both stroke incidence and mortality. Future studies should explore whether hyperuricemia is a modifiable risk factor for stroke.

Hyperuricemia and the risk for coronary heart disease morbidity and mortality a systematic review and dose-response meta-analysis.

Considerable controversy exists regarding the association between hyperuricemia and coronary heart disease (CHD). Therefore, we performed a systematic review and dose-response meta-analysis of prospective studies to examine the controversy. Prospective cohort studies with relative risks (RRs) and 95% confidence intervals (CIs) for CHD according to serum uric acid levels in adults were eligible. A random-effects model was used to compute the pooled risk estimate. The search yielded 29 prospective cohort studies (n = 958410 participants). Hyperuricemia was associated with increased risk of CHD morbidity (adjusted RR 1.13; 95% CI 1.05 to 1.21) and mortality (adjusted RR 1.27; 95% CI 1.16 to 1.39). For each increase of 1 mg/dl in uric acid level, the pooled multivariate RR of CHD mortality was 1.13 (95% CI 1.06 to 1.20). Dose-response analysis indicated that the combined RR of CHD mortality for an increase of 1 mg uric acid level per dl was 1.02 (95% CI 0.84 to 1.24) without heterogeneity among males (P = 0.879, I2 = 0%) and 2.44 (95% CI 1.69 to 3.54) without heterogeneity among females (P = 0.526, I2 = 0%). The increased risk of CHD associated with hyperuricemia was consistent across most subgroups. Hyperuricemia may increase the risk of CHD events, particularly CHD mortality in females.

Obstructive sleep apnea and risk of stroke: A meta-analysis of prospective studies

Stroke is the second leading cause of death worldwide [1]. 78% of strokes are first attacks [2], and about 780,000 Americans experience a new or recurrent stroke each year, on average, one stroke every 40 s [3]. Any possible means to prevent stroke should, therefore, be a key public health priority. Obesity is one of the leading risk factors for stroke and a target for stroke prevention [4,5]. Interestingly, human observational studies strongly suggest that obesity is the most important risk factor for obstructive sleep apnea (OSA), which is characterized by repeated obstructions of the upper airway during sleep which result in oxygen desaturations and alterations in blood pressure and cerebral blood flow [6]. Whether OSA independently increases stroke incidences, or whether this relationship is confounded by this populations prevalent cardiovascular risk factors, remains debated. The latest published metaanalysis of 12 prospective cohort studies showed a significant positive association between OSA and fatal and non-fatal stroke (pooled relative risk = 2.15, 95% confidence interval: 1.42–3.24) [7]. However, that meta-analysis found insufficient evidence in the subgroup meta-analyses by type of prevention, study design, geographical area, duration of follow-up, and methodological quality. Therefore, we carried out a meta-analysis of cohort studies to systematically identify whether OSA independently increases the risk of fatal or non-fatal stroke. We followed standard criteria for the performing and reporting of the meta-analyses of observational studies [8]. A systematic search of published articles (through 26 September 2013) was performed by using electronic databases including PubMed, Cochrane Library, and ISI Web of Science databases. We used the following keywords: sleep disordered breathing, obstructive sleep apnea, OSA, sleep apnea, stroke, cerebral infarction, cerebrovascular disease, hemorrhage, cardiovascular disease, coronary artery disease, prospective study, cohort study, and follow-up study. There were no language restrictions. Studies were included for the metaanalysis if they fulfilled the following criteria: (1) the study of adult patients had a community-based or population-based or clinicbased, prospective cohort design; (2) the exposed population was patients with OSA; (3) reported quantitative estimates of the multivariate-adjusted relative risk (RRs) and 95% confidence intervals (CIs) for stroke associated with OSA, hazard ratio/odds ratios were considered equivalent to RRs; and (4) longer than 1 year of follow-up. Studies were excluded if they fulfilled the following criteria: (1) the study design was a nonprospective cohort (for example, cross-sectional and retrospective case–control studies); (2) unadjusted RRs and 95% CIs were reported; and (3) shorter than 1 year of follow-up. The Newcastle–Ottawa Scale (NOS) was used to assess the quality of studies [9]. A maximum of 9 points can be given for each study in the categories of selection, outcome, and comparability. We defined studies of high or low quality based on the median overall score among all studies. The RRs were pooled using the random-effects model [10]. All the statistical analyses were performed in Stata 11 (StataCorp LP, College Station, TX). P values were 2-sided and p b 0.05 was considered statistically significant. Ten cohort studies met the inclusion criteria [11–20] (Fig. 1). The main characteristics of studies in the meta-analysis were presented in Tables 1A and 1B. A total of eleven comparisons (one study did have sex specific data) investigated the association between OSA and risk of stroke. The ascertainment of stroke, duration of follow up, study design, assessment of OSA, and methodological quality varied across studies. Pooling all 11 comparisons, OSAwas associated with a significantly increased risk of fatal or non-fatal stroke (RR, 2.10; 95% CI, 1.50 to 2.93; p = 0.000) (Fig. 2). Fig. 3 showed the pooled RR for stroke stratified by history of stroke, study design, geographical area, duration of follow-up, and methodological quality. The RR for primary prevention studies was 2.06 (95% CI 1.53–2.79; p = 0.000). Increases in stroke events were also found in the subgroup of study design (clinic-based study: RR 2.44, 95% CI 1.24– 4.80, p = 0.010; and population-based study: RR 2.13, 95% CI 1.45– 3.13, p = 0.000, respectively). In addition, we found significant

Schizophrenia and risk of stroke: a meta-analysis of cohort studies.

Min Li , Ying-Li Fan , Zhen-Yu Tang ⁎, Xiao-Shu Cheng ⁎⁎ a Department of Neurology, Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China b Department of Cardiovascular, Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China c Department of Cardiovascular, Institute of Cardiovascular Disease, Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China

Association between Gamma-Glutamyltransferase Level and Risk of Stroke: A Systematic Review and Meta-analysis of Prospective Studies

BACKGROUND Stroke is often regulated by a number of modifiable and nonmodifiable risk factors. Recently, studies suggested high gamma-glutamyltransferase (GGT) level may be associated with stroke, but drew inconsistent conclusions. So, we conducted a meta-analysis to evaluate the relationship between GGT level and risk of stroke. METHODS We systematically searched PubMed, Embase, and Cochrane Library (updated to January 2015) for prospective cohort studies. Then, relative risk (RR) with 95% confidence interval (CI) was used to assess the association. Regression analyses, subgroup analyses, and sensitivity analyses were also performed. The Begg test, Egger test, and the trim-and-fill method were used to assess potential publication bias. RESULTS A total of 5707 cases and 926,497 participants in 10 prospective studies were included. Overall, high GGT level has a positive association with increased risk of stroke (RR = 1.28; 95% CI, 1.16-1.43). In the subgroup analyses, a positive association was consistently observed in each subgroup except in the women subgroup (RR = 1.45; 95% CI, .9-2.34) and a large number of stroke events subgroups (≥ 500) (RR = 1.25; 95% CI, .85-1.84). Heterogeneity was significantly reduced in the subgroup analysis by population characteristics. In the publication bias test, the resulting adjusted RR remained significant (RR = 1.10; 95% CI, 1.00-1.21) after using the trim-and-fill method. CONCLUSIONS Our meta-analysis provides evidence that a high level of GGT is significantly associated with increased risk of stroke independently of alcohol intake. Gender and ethnicity variations may exist in the relationship between high GGT level and risk of stroke.

Dietary flavonoid intake and the risk of stroke: a dose-response meta-analysis of prospective cohort studies

Objective To clarify and quantify the potential association between intake of flavonoids and risk of stroke. Design Meta-analysis of prospective cohort studies. Data source Studies published before January 2016 identified through electronic searches using PubMed, Embase and the Cochrane Library. Eligibility criteria for selecting studies Prospective cohort studies with relative risks and 95% CIs for stroke according to intake of flavonoids (assessed as dietary intake). Results The meta-analysis yielded 11 prospective cohort studies involving 356 627 participants and more than 5154 stroke cases. The pooled estimate of the multivariate relative risk of stroke for the highest compared with the lowest dietary flavonoid intake was 0.89 (95% CI 0.82 to 0.97; p=0.006). Dose-response analysis indicated that the summary relative risk of stroke for an increase of 100 mg flavonoids consumed per day was 0.91 (95% CI 0.77 to 1.08) without heterogeneity among studies (I2=0%). Stratifying by follow-up duration, the relative risk of stroke for flavonoid intake was 0.89 (95% CI 0.81 to 0.99) in studies with more than 10 years of follow-up. Conclusions Results from this meta-analysis suggest that higher dietary flavonoid intake may moderately lower the risk of stroke.

Impact of Retinal Vein Occlusion on Stroke Incidence: A Meta‐Analysis

Background Considerable controversy exists on the association between retinal vein occlusion (RVO) and stroke risk. Therefore, we conducted a meta‐analysis to assess the relationship between RVO and stroke risk. Methods and Results PubMed, EMBASE, and the Cochrane library databases were searched for cohort studies with data on RVO and stroke risk. Studies that reported adjusted relative risks (RRs) with 95% CIs of stroke associated with RVO were included. Stratified analyses were conducted according to key characteristics. A total of 5 articles including results from 6 prospective cohort studies with 431 cases of stroke and 37 471 participants were included in the meta‐analysis. Overall, after adjustment for established cardiovascular risk factors, participants with RVO at baseline were considerably more associated with a greater incidence of stroke risk (combined RR: 1.50, 95% CI: 1.19–1.90), compared to participants without RVO. The results were more pronounced for stroke (RR: 1.72, 95% CI: 1.24–2.37) in the stratified with a stroke history. The risk of stroke was nonsignificant in male subjects (RR: 1.20, 95% CI: 0.96–1.49) and in female subjects (RR: 0.93, 95% CI: 0.64–1.34). The presence of both central RVO (RR: 1.90, 95% CI: 1.46–2.48) and branch RVO (RR: 1.79, 95% CI: 1.18–2.72) was associated with increased risk of stroke. Stratifying by age, the associations between RVO and risk of stroke were similar between the age range in the cohorts that ranged from 50 to 59 years and 60 to 69 years. Conclusions Exposure to RVO was associated with an increased risk of stroke, especially in subjects aged between 50 and 69 years. Future studies on the effect of RVO treatment and modifiable risk factor reduction on stroke risk in RVO patients are warranted.

Uric Acid for Acute Stroke: Fantasy or Reality?

lenges whether or not SUA is indeed effective for stroke. A consensus recommendation has been made that the preclinical neuroprotectant should show efficacy in at least 2 species and in 2 laboratories using different models [10] . It is therefore imperative to explore the attendant concerns. First of all, experimental studies that assess SUA in animal models of ischemic stroke should preferably have a longer time window. Furthermore, the assessment of infarct volume and neurological scores should be masked. It is necessary to examine higher-quality prospective evidence on the relationship between SUA and the shortand long-term outcomes of stroke. In summary, certain recommendations should be considered for the efficacy of SUA in the treatment of acute ischemic stroke. Large prospective studies conducted with the use of standardized outcome measures as well as the timing of SUA sampling are necessary to assess the association of SUA and stroke outcome. Dear Editor, Stroke is the second most common cause of death, as well as the fourth leading cause of lost productivity and a major cause of disability worldwide [1] . Hence, stroke-related morbidity and mortality are one of the main public health concerns as the treatment options for patients with acute stroke are limited. Although intravenous alteplase (recombinant tissue plasminogen activator) administered within 4.5 h after the onset of symptoms is the preferred treatment for ischemic stroke in Europe [2] , the condition of many patients does not improve significantly after receiving this therapy [3] . Therefore, the identification of new therapeutic approaches and treatments to ameliorate the long-term outcomes of stroke patients is required. Serum uric acid (SUA) is a final enzymatic product of purine metabolism [4] . There is a well-recognized epidemiological link between elevated SUA levels and the increased risk of stroke morbidity and mortality [5] . On the other hand, animal models of acute ischemic stroke have shown that SUA may be neuroprotective [6] , but the evidence for this is limited. In the past several decades, a number of clinical studies have assessed the association between SUA and stroke outcome [7, 8] . However, the role of SUA in shortand long-term outcomes is still controversial. A possible explanation for the varying effects of SUA in the acute phase of ischemic stroke could be that different outcome measures, study size and population are used in the different studies, thereby hampering the comparison of the findings. Recently, Chamorro et al. [9] reported that the addition of SUA to thrombolytic therapy did not increase the proportion of patients who achieved an excellent outcome (according to the modified Rankin scale score at 90 days) after stroke compared to patients receiving placebo. This recent controversial report chalReceived: August 17, 2014 Accepted: October 22, 2014 Published online: December 3, 2014

Peripherally Inserted Central Catheter: How Safe Is It for Acute Myeloid Leukemia Patients?

catheter-related local infection. A retrospective study by Strahilevitz et al. [9] evaluated the associated complications and their significance with regard to catheter removal. Fifty-two PICCs were inserted in 40 patients with AML. This study demonstrated that PICC provided effective long-term vascular access in patients with AML. As the authors acknowledged, their study had several limitations. First, it was a retrospective study. It could only demonstrate that PICC provided long-term vascular access with a relatively low complication rate, but could not prove a potential for error in the reporting of complications (e.g., infections, phlebitis and others). Second, at present, it is difficult to compare the complication rate among different series because the definitions and diagnostic techniques of complications vary [8] . How safe is PICC for AML patients? In conclusion, a strong body of evidence has shown that PICC provided long-term vascular access with an acceptable complication rate in patients with AML. Future studies, preferably randomized trials comparing PICCs with other catheters, are required, and the following potential measures should be considered: (1) Using a smaller-diameter PICC may reduce vascular damage; meanwhile, it is plausible that antibioticimpregnated surfaces of the catheter may reduce the rate of infectious complications [10] . (2) Rapid diagnostic techniques and unified definitions of complications are warranted to determine whether or not PICC can be considered an acceptable catheter for AML patients. (3) Prospective clinical trials could explore whether the use of PICC may decrease the rate of complications. Dear Editor, Safe and reliable vascular access is essential for the treatment of patients with acute myeloid leukemia (AML). During the past decade, a systematic exploration of the countless barriers to achieve this goal has been undertaken. The use of indwelling central venous catheters (CVCs) has significantly enhanced the administration of drugs to AML patients [1] . Clearly, the maintenance of long-term intravenous routes is one critical element minimizing CVC-related complications (such as infection, fibrin sheath formation and thrombosis) [2] . A peripherally inserted central catheter (PICC) may help eliminate potentially life-threatening complications (e.g., hemothorax). It provides an alternative to subclavian or jugular vein catheterization and reduces the likelihood of arterial puncture and hemorrhage [3] . In addition, it is deemed a relatively simpler, safer and easier alternative to central venous routes [2] . The number of PICC placements in the USA, for example, has been estimated to over a million per year [4] . The most obvious advantage of PICC is its long-term dwell time for long-term antibiotic administration to prevent CVC-related infections [5] . However, this is a doubleedged sword. A catheter-related infection results in a cost increase of USD 6,000 per treatment because of prolonged hospitalization by on average 7 days [6] . This creates a modern-day health burden. Although PICCs for cancer patients have been used for many years, few data are available on patients affected with AML. Interestingly, a prospective study by Karthaus et al. [7] found that the incidence of CVC-related infections was low in patients with acute leukemia undergoing intensive chemotherapy. The authors observed the frequency of localized infection at the insertion site of all the patients (n = 58) treated for acute leukemia. Catheters were inserted into the subclavian or jugular vein. Although the overall incidence of CVC infections in acute leukemia patients was only 6.5 per 1,000 catheter days, the criterion for the diagnosis of intravascular catheter-related infections was the roll plate method. In 2001, the guidelines by Mermel et al. [8] reported that the roll plate method will be quite sensitive in the identification of a recently inserted catheter (duration of placement <1 week). However, in the trial of Karthaus et al. [7] , the catheters remained in place for a mean of 14.5 days (>1 week), i.e. the roll plate method was less sensitive. Therefore, the results of this trial need to be interpreted with caution, mainly because of its limitation in diagnostic technique. In AML patients, the difficulty associated with the reinsertion of a CVC may result in a decision that could increase the risks of Received: June 24, 2014 Accepted: July 23, 2014 Published online: September 6, 2014