Platelet indices and erectile dysfunction: A systematic review and meta‐analysis

Elevated platelet levels have been postulated to be associated with cardiovascular diseases, conditions closely linked to erectile dysfunction (ED). The current systematic review and meta‐analysis was performed to assess the platelet indices, which including platelet count (PLT), mean platelet volume (MPV) and platelet distribution width (PDW) in subjects with ED compared to controls in an attempt to clarify the possible role of platelet indices in the pathogenesis of ED. We initially screened the candidate studies observing the possible association between platelet indices and ED following literature search of database Cochrane Library, PubMed, EMBASE and MEDLINE and therefore included the studies based on the pre‐defined inclusion and exclusion criteria. Two independent investigators extracted the related information on article data and outcome measures from the qualified studies, and a meta‐analysis was therefore performed using Stata 12.0 software. Subgroup analyses were conducted by the different ED aetiology obtained from the eligible studies. The standard mean difference (SMD) and the corresponding 95% confidence intervals (95% CIs) were applied to estimate the outcome measures. A total of 14 articles were qualified in our meta‐analysis with a total of 1595 cases and 987 controls included. Pooled estimate was in favour of increased MPV levels in subjects with ED with a SMD of 0.651 fl, 95% CI 0.567–0.735, p = 0.000. Subgroup analysis showed that vasculogenic ED had a higher MPV levels than controls as well (SMD [95% CI] = 1.026 [0.823–1.228], p = 0.000). However, pooled analysis based on PLT and PDW levels has produced inconsistent results and not strong evidence on platelet level and ED correlation. In conclusion, vasculogenic ED patients had a higher MPV level in our study. However, the results need further interpretation with caution and more high‐quality studies are warranted.     

Serum vitamin D levels and erectile dysfunction: A systematic review and meta‐analysis

Suboptimal levels of serum vitamin D levels have been implied to be associated with cardiovascular diseases and endothelial dysfunction, conditions closely associated with erectile dysfunction (ED). The present systematic review and meta‐analysis was performed to evaluate the vitamin D levels in subjects with ED compared to controls and the 5‐item version of the international index of erectile function (IIEF‐5) score in subjects with vitamin D deficiency compared to those without vitamin D deficiency in order to elucidate the role of vitamin D in the pathogenesis of ED. Studies evaluating the possible association between vitamin D levels and ED were initially screened and thus included following electronic literature search of database Cochrane Library, PUBMED, EMBASE and MEDLINE. Essential article information including outcome measures was extracted from the qualified studies by two independent authors, and STATA 12.0 software was used conducted the meta‐analysis. Subgroup analyses were conducted by vitamin D detection methods and sample size. The standard mean difference (SMD) as well as the 95% confidence intervals (95% CIs) was applied to estimate the outcome measures. A total of seven articles were included in our meta‐analysis with a total of 4,132 subjects. Pooled estimate was in favour of increased vitamin D levels in subjects without ED with a SMD of 3.027 ng/ml, 95%CI 2.290–3.314, p = 0.000. However, subgroup analysis showed an opposite trend, after one study with a sample size over 1,000 that could possibly influence the weight balance was excluded, with a SMD of 0.267, 95%CI ?0.052 to 0.585, p = 0.101. We also identified about 0.320 higher in IIEF‐5 score (95%CI = 0.146–0.494, p = 0.000) in subjects without vitamin D deficiency versus with vitamin D deficiency. Nevertheless, subgroup analysis based on vitamin D detection methods obtained differential results (radioimmunoassay subgroup, SMD(95%CI) = 0.573 (0.275–0.870), p = 0.000; immunoassay subgroup, SMD(95%CI) = 0.189 (?0.025 to 0.404), p = 0.084). In conclusion, results from the present meta‐analysis did not provide a strong relationship between vitamin D and the risk of ED. However, the results should be interpreted with caution and more high quality studies are warranted.     

Trazodone for erectile dysfunction: a systematic review and meta-analysis

OBJECTIVE: To determine the efficacy and safety of trazodone in the treatment of erectile dysfunction (ED) in a meta-analysis. METHODS: The data sources used were Medline and the Cochrane Library databases (January 1966 to May 2002), bibliographies of retrieved articles and review articles, and conference proceedings and abstracts. Trials were eligible for inclusion in the review if they included men with ED, compared trazodone with a control, were randomized, of > or = 7 days' duration and assessed clinically relevant outcomes. Two reviewers independently evaluated study quality and extracted data in a standardized fashion. RESULTS: Six trials (comprising 396 men) met the inclusion criteria; they consisted of heterogeneous populations, were small, brief and in some cases methodologically weak. Three of the six trials showed an apparently clinically meaningful benefit of trazodone for ED compared with placebo, the differences being statistically significant in two. In pooled results, trazodone monotherapy appeared more likely than placebo to lead to a 'positive treatment response', although this difference was not statistically significant (37% vs 20%; relative benefit increase, 1.6; 95% confidence interval, CI, 0.8-3.3). Subgroup analyses suggested that men with psychogenic ED might be more likely to benefit from trazodone than those with mixed or physiological ED. The efficacy of trazodone also appeared greater at higher doses (150-200 vs 50 mg/day). Men randomized to trazodone were not significantly more likely than those receiving placebo to withdraw for any reason or for an adverse event, or to have specific adverse events, but wide CIs could not exclude a greater risk of these adverse outcomes with trazodone. Specific adverse events with trazodone included dry mouth (19%), sedation (16%), dizziness (16%) and fatigue (15%). CONCLUSION: Trazodone may be helpful in men with ED, possibly more so at higher doses, and in men with psychogenic ED. Future high-quality trials should compare trazodone with placebo and other therapies in men with depression and psychogenic ED.     

Hypertension might be a risk factor for erectile dysfunction: a meta‐analysis

The study aimed to evaluate whether hypertension was a risk factor for erectile dysfunction (ED). Databases including PubMed and Embase were retrieved to identify studies related to hypertension in ED patients. Odds ratio (OR) and 95% confidence interval (CI) were used as the effect size. Subgroup analyses stratified by total number of enrolled subjects and research regions were performed. Sensitivity analysis was performed by removing a single study at one time. Egger's test was used to evaluate the publication bias. Totally, 40 studies including 121,641 subjects were included in the meta‐analysis. As a result, hypertension was closely related to ED (OR = 1.74, 95% CI, 0.63–0.80, p < .01). Subgroup analysis indicated hypertension was the risk factor for ED whatever the participants numbers. When stratified by different regions, hypertension was a risk factor for ED in Africa (OR = 3.35, 95% CI, 1.45–7.77, p < .01), Americas (OR = 1.97, 95% CI, 1.68–2.31, p < 0.01), Asia (OR = 1.46, 95% CI, 1.16–1.84, p < .01) and Europe (OR = 1.83, 95% CI, 1.34–2.49, p < .01), but not in Australia. Hypertension may be a potential risk factor for ED.     

Intraoperative ketamine administration to prevent delirium or postoperative cognitive dysfunction: A systematic review and meta‐analysis

Background

Postoperative cognitive complications are associated with substantial morbidity and mortality. Ketamine has been suggested to have neuroprotective effects in various settings. This systematic review evaluates the effects of intraoperative ketamine administration on postoperative delirium and postoperative cognitive dysfunction (POCD).

Methods

Medline, Embase and Central were searched to 4 March 2018 without date or language restrictions. We considered randomised controlled trials (RCTs) comparing intraoperative ketamine administration versus no intervention in adults undergoing surgery under general anaesthesia. Primary outcomes were postoperative delirium and POCD. Non‐cognitive adverse events, mortality and length of stay were considered as secondary outcomes. Data were independently extracted. The quality of the evidence (GRADE approach) was assessed following recommendations from the Cochrane collaboration. Risk ratios were calculated for binary outcomes, mean differences for continuous outcomes. We planned to explore the effects of age, specific anaesthesia regimen, depth of anaesthesia and intraoperative haemodynamic events through subgroup analyses.

Results

Six RCTs were included. The incidence of postoperative delirium did not differ between groups (4 trials, 557 patients, RR 0.83, 95% CI [0.25, 2.80]), but patients receiving ketamine seemed at lower risk of POCD (3 trials, 163 patients, RR 0.34, 95% CI [0.15, 0.73]). However, both analyses presented limitations. Therefore, the quality of the evidence (GRADE) was deemed low (postoperative delirium) and very low (POCD).

Conclusion

The effect of ketamine on postoperative delirium remains unclear but its administration may offer some protection towards POCD. Large, well‐designed randomised trials are urgently needed to further clarify the efficacy of ketamine on neurocognitive outcomes.

     

Impact of preoperative atrial fibrillation in patients with left ventricular assist device: A systematic review and meta‐analysis

Atrial fibrillation (AF) is a common finding in patients evaluated for left ventricular assist device (LVAD). There is conflicting data regarding the mortality risk as well as the thromboembolic risk in patients with preoperative AF who undergo LVAD implantation. We examined these risks by performing a meta‐analysis. We performed a literature search of Pubmed, EMBASE, SCOPUS, and Cochrane from inception to February 2018. The eligible studies were used to compare mortality rate and thromboembolic risk between AF and Non‐AF (NAF) groups after LVAD implantation. We obtained 391 articles from our search strategy. Seven retrospective studies were included and accounted for 5823 LVAD patients (AF 1589; NAF 4234). The median follow‐up duration ranged from 7–24 months. The pooled analysis revealed a significantly increased risk of mortality in preoperative AF patients who underwent LVAD operation compared to those with NAF (Risk Ratio [RR] 1.16, 95% CI 1.05‐1.28, I2 = 0%). Five studies reported thromboembolism events involving 1359 preoperative AF and 3893 NAF patients. The pooled analysis did not show a statistically significant association between risk of thromboembolic event and preoperative AF (Risk Ratio [RR] 1.08, 95% CI 0.86‐1.36, I2 = 76.2%). Our study shows that preoperative AF may be associated with a higher mortality rate. This study is limited by the fact that the data are pooled from retrospective studies. Further prospective studies are warranted in order to validate these results.     

Mean platelet volume,platelet distribution width and platelet count in erectile dysfunction: A systematic review and meta‐analysis

The aim of this study was to investigate the relationship between mean platelet volume (MPV), platelet distribution width (PDW), platelet count (PC) and erectile dysfunction (ED). We searched for observational studies from PubMed, EMBASE, Web of Science and CNKI up to 31 March 2016. Two reviewers independently selected the studies and extracted the data. MPV, PDW, and PC and mean differences in these platelet indices between healthy subjects and ED patients were explored using the Comprehensive Meta‐Analysis software package. Seven studies including 795 patients and 524 healthy subjects met the inclusion criteria. The MPV was significantly larger in patients with ED than controls with the standardised mean difference of 0.596 fL (95% CI: 0.378, 0.815, p < 0.001). In ED patients, the pooled mean difference in MPV between vasculogenic ED patients and nonvasculogenic ED patients was 0.706 fL in case–control studies (95% CI: 0.410, 1.002, p < 0.001). There was no significant difference in PDW and PC between healthy subjects and ED patients. The available data suggest that larger MPV was associated with ED. Patients with vasculogenic ED tend to have higher MPV than nonvasculogenic ED patients. Further studies are needed to assess whether increased MPV in ED patients is associated with increased cardiovascular disease.     

Quantifying cognitive dysfunction across the spectrum of end‐stage kidney disease: A systematic review and meta‐analysis

Cognitive dysfunction is reportedly highly prevalent among chronic kidney disease (CKD) patients. A variety of screening tools and neuropsychiatric batteries are used to quantify the magnitude and nature of this dysfunction. Our objective is to summarize the neurocognitive testing used, and determine what degree cognitive dysfunction is reported in CKD patients. All study designs published in English that contained participants who were either pre‐dialysis patients, haemodialysis (HD) or peritoneal dialysis (PD) patients or renal transplant recipients were considered. Reported comparative non‐CKD control data was also collected. All study designs were included. The search period encompassed articles from 1980 to May 2018. This review is registered with PROSPERO (CRD42018096568). Of the 1711 articles screened, 148 articles were relevant and used in the meta‐analysis. Commonly used assessments were The Mini–Mental State Examination (MMSE), The Modified Mini–Mental State Examination, the Trails Making Tests (TMT) forms A and B and components of the Wechsler Adult Intelligence Scale: Digit Span and Digit Symbol. Means for all assessments were adjusted using a random effects model to account for the differences in variance. Adjusted mean MMSE scores were significantly lower for both pre‐dialysis (26.08, n = 17 073) and HD (26.31, n = 3314) patients when compared to non‐CKD controls (28.21, n = 5226). PD (58.01 s, n = 859) and HD (56.04 s, n = 2344) patients also took significantly longer to complete the Trails Making Task A than non‐CKD controls (37.62 s, n = 4809). Patients with CKD, especially pre‐dialysis and those requiring dialysis, are likely to exhibit impairments in cognition that can be identified with specific screening neuropsychological assessments.     

Treatment outcomes of bumetanide continuous infusion: A systematic review and meta‐analysis

The clinical use of continuous bumetanide infusion for acute heart failure and volume overload is common. However, there is not enough supporting evidence for the use of continuous bumetanide infusion. Thus, we conducted this systematic review and meta‐analysis aiming to describe the treatment outcomes of continuous bumetanide infusion. We searched Ovid MEDLINE, EMBASE and the Cochrane Library for eligible publications. Inclusion criteria were patients age ≥18 years with bumetanide infusion for heart failure, acute kidney injury (AKI) or volume overload. From 1564 citations, three studies (n = 94 patients) were included in the systematic review and meta‐analysis. The mean dose of bumetanide was 1.08 ± 0.43 mg/hour with a mean treatment duration of 45.09 ± 10.12 hours. Mean urine output in response to continuous bumetanide infusion was 1.88 mL/kg/hour (95% confidence interval [CI], 1.72‐2.05). The incidence of AKI with continuous bumetanide infusion was 24.7% (95% CI, 8.2‐54.6). By using Pearson's correlation coefficient, increasing doses of bumetanide were correlated with increased urine output (P = .026) and increased incidence of AKI (P < .01). There was no correlation between increasing urine output and the incidence of AKI (P = .739). In conclusion, with available evidence, continuous bumetanide infusion may be used in the treatment of acute heart failure or volume overload with close monitoring for new‐onset or worsening AKI.     

The effect of antiplatelet therapy on survival and cardiac allograft vasculopathy following heart transplantation: A systematic review and meta‐analysis

Cardiac allograft vasculopathy (CAV) is mediated by endothelial inflammation, platelet activation and thrombosis. Antiplatelet therapy may prevent the development of CAV. This systematic review and meta‐analysis summarizes and appraises the evidence on the effect of antiplatelet therapy after heart transplantation (HT). CENTRAL(Ovid), MEDLINE(Ovid), Embase(Ovid) were searched from inception until April 30, 2020. Outcomes included CAV, all‐cause mortality, and CAV‐related mortality. Data were pooled using random‐effects models. Seven observational studies including 2023 patients, mean age 52 years, 22% female, 47% with ischemic cardiomyopathy followed over a mean 7.1 years proved eligible. All studies compared acetylsalicylic acid (ASA) to no treatment and were at serious risk of bias. Data from 1911 patients in 6 studies were pooled in the meta‐analyses. The evidence is very uncertain about the effect of ASA on all‐cause or CAV‐related mortality. ASA may reduce the development of CAV (RR 0.75, 95% CI: 0.44–1.29) based on very low certainty evidence. Two studies that conducted propensity‐weighted analyses showed further reduction in CAV with ASA (HR 0.31, 95% CI: 0.13–0.74). In conclusion, there is limited evidence that ASA may reduce the development of CAV. Definitive resolution of the impact of antiplatelet therapy on CAV and mortality will require randomized clinical trials.     

Impact of pretransplant recipient body mass index on post heart transplant mortality: A systematic review and meta‐analysis

The ISHLT's 2016 Guidelines on the selection of heart transplant (HT) candidates recommends weight loss prior to listing for persons with body mass (BMI) index greater than 35 kg/m². We conducted a systematic review to assess the impact of BMI on all‐cause mortality. We searched to identify eligible observational studies that followed HT recipients. We used the GRADE system to quantify absolute effects and quality of evidence, and meta‐analyzed survival curves to assess post‐transplant mortality across BMI categories. We found a significantly increased risk of mortality in patients with BMI > 30 kg/m² across all age categories, independently of transplant era and study source (BMI 30‐34.9: HR 1.10, 95% CI 1.04‐1.17; BMI ≥ 35: HR 1.24, 95% CI 1.12‐1.38). We also found an increased risk of death in underweight (BMI < 18.5 kg/m²) candidates over 39 years of age (Age 40‐65: HR 1.24, 95% CI 1.02‐1.53; Age > 65: HR 1.70, 95% 1.13‐2.57). We found obesity and underweight BMI to be associated with mortality post‐HT. The similar and overlapping increased risk of mortality in patients with BMI 30‐34.9 and BMI ≥ 35 does not support the recently updated ISHLT guidelines. Future evidence in the form of randomized controlled trials is required to assess effectiveness of interventions targeting obesity‐related comorbidities and weight management.