Adjunctive Medical Therapy with α-Blocker after Extracorporeal Shock Wave Lithotripsy of Renal and Ureteral Stones: A Meta-Analysis

Background

Although some trials assessed the efficacy and safety of the α-blocker in facilitating renal and ureteral stones expulsion after extracorporeal shock wave lithotripsy (ESWL), the role of the α-blocker in facilitating upper urinary calculi expulsion after ESWL remain controversial.

Aims

To determine the efficacy and safety of the α-blocker in facilitating renal and ureteral stones expulsion after ESWL.

Methods

A literature search was carried out using the PubMed database, EMBASE and the Cochrane Library database to identify relevant studies. Two reviewers independently extracted data and assessed methodological quality. Pooled effect estimates were obtained using a fixed- and random-effects meta-analysis.

Results

The meta-analysis included 23 RCTs, α-blocker significantly enhanced expulsion rate of upper urinary tract calculi after ESWL (P<0.00001; RR 1.21; 95% CI 1.12–1.31), significantly promoted steinstrasse expulsion (P=0.03; RR 1.25; 95% CI 1.03–1.53), significantly shortened the discharge time of upper urinary tract calculi (P=0.0001; MD -2.12; 95% CI -3.20–-1.04), significantly reduced the patient''s pain VAS score (P=0.001; RR -1.0; 95% CI -1.61–-0.39). Compared with the control group, dizziness (P=0.002; RR 5.48; 95% CI 1.91–15.77), anejaculation (P=0.02; RR 12.17; 95% CI 1.61–91.99) and headache (P=0.04; RR 4.03; 95% CI 1.04–15.72) in the α-blocker group was associated with a higher incidence.

Conclusions

Treatment with α-blocker after ESWL appears to be effective in enhancing expulsion rate of upper urinary tract calculi, shortening the discharge time of upper urinary tract calculi, reducing the patient''s pain. The side effects of α-blocker were light and few.     

Dezocine for Preventing Postoperative Pain: A Meta-Analysis of Randomized Controlled Trials

Background

Dezocine is considered to be an alternative medication for managing postoperative pain. The aim of this study was to assess the efficacy and safety of this drug in this regard.

Methods

Medline, EMBASE and the Cochrane Central Register of Control Trials (CENTRAL) were searched to identify all randomized controlled trials (RCTs) that compare dezocine with placebo or dezocine with morphine on postoperative pain. The data were extracted and pooled using Mantel-Haenszel random effects model. Heterogeneity was tested using the I ² statistic with values >50% and Chi² test with P ≤ 0.05 indicating obvious heterogeneity between the studies.

Results

Seven trials evaluating 665 patients were included. The number of patients with at least 50% pain relief was increased (N = 234; RR 3.04, 95% CI 2.27 to 4.08) and physician (N = 465; RR 2.84, 95% CI 1.66 to 4.84) and patient satisfaction (N = 390; RR 2.81, 95% CI 1.85 to 4.26) were improved following the administration of dezocine compared with the placebo. The effects of dezocine were similar to those of morphine in terms of the number of patients reporting at least 50% pain relief within 2–6 h after surgery (N = 235; RR 1.29, 95% CI 1.15 to 1.46) and physician (N = 234; RR 1.18, 95% CI 0.93 to 1.49) and patient (N = 158; RR 1.33, 95% CI 0.93 to 1.92) satisfaction. While, the number of patients with at least 50% pain relief within 0–1 h after surgery increased following dezocine compared with morphine treatment (N = 79; RR 1.45, 95% CI 1.18 to 1.77). There was no difference in the incidence of postoperative nausea and vomiting (PONV) following dezocine treatment compared with the placebo (N = 391; RR 1.06, 95% CI 0.42 to 2.68) or morphine treatment (N = 235; RR 0.65, 95% CI 0.14 to 2.93).

Conclusion

Dezocine is a promising analgesic for preventing postoperative pain, but further studies are required to evaluate its safety.     

A Single-Dose Intra-Articular Morphine plus Bupivacaine versus Morphine Alone following Knee Arthroscopy: A Systematic Review and Meta-Analysis

Objectives

The purpose of this study was to compare the efficacy and safety of a single-dose intra-articular morphine plus bupivacaine versus morphine alone in patients undergoing arthroscopic knee surgery.

Methods

Randomized controlled trials comparing a combination of morphine and bupivacaine with morphine alone injected intra-articularly in the management of pain after knee arthrocopic surgery were retrieved (up to August 10, 2014) from MEDLINE, the Cochrane Library and Embase databases. The weighted mean difference (WMD), relative risk (RR) and their corresponding 95% confidence intervals (CIs) were calculated using RevMan statistical software.

Results

Thirteen randomized controlled trials were included. Statistically significant differences were observed with regard to the VAS values during the immediate period (0-2h) (WMD -1.16; 95% CI -2.01 to -0.31; p = 0.007) and the time to first request for rescue analgesia (WMD = 2.05; 95% CI 0.19 to 3.92; p = 0.03). However, there was no significant difference in the VAS pain score during the early period (2-6h) (WMD -0.36; 95% CI -1.13 to 0.41; p = 0.35), the late period (6-48h) (WMD 0.11; 95% CI -0.40 to 0.63; p = 0.67), and the number of patients requiring supplementary analgesia (RR = 0.78; 95% CI 0.57 to 1.05; p = 0.10). In addition, systematic review showed that intra-articular morphine plus bupivacaine would not increase the incidence of adverse effects compared with morphine alone.

Conclusion

The present study suggested that the administration of single-dose intra-articular morphine plus bupivacaine provided better pain relief during the immediate period (0-2h), and lengthened the time interval before the first request for analgesic rescue without increasing the short-term side effects when compared with morphine alone.

Level of Evidence

Level I, meta-analysis of Level I studies.     

The Efficacy of Shugan Jianpi Zhixie Therapy for Diarrhea-Predominant Irritable Bowel Syndrome: A Meta-Analysis of Randomized,Double-Blind,Placebo-Controlled Trials

Background

Shugan Jianpi Zhixie therapy (SJZT) has been widely used to treat diarrhea-predominant irritable bowel syndrome (IBS-D), but the results are still controversial. A meta-analysis of randomized, double-blind, placebo-controlled trials was performed to assess the efficacy and tolerability of SJZT for IBS-D.

Methods

The MEDLINE, EMBASE, Cochrane Library, the China National Knowledge Infrastructure database, the Chinese Biomedical Literature database and the Wanfang database were searched up to June 2014 with no language restrictions. Summary estimates, including 95% confidence intervals (CI), were calculated for global symptom improvement, abdominal pain improvement, and Symptom Severity Scale (BSS) score.

Results

Seven trials (N=954) were included. The overall risk of bias assessment was low. SJZT showed significant improvement for global symptom compared to placebo (RR 1.61; 95% CI 1.24, 2.10; P =0.0004; therapeutic gain = 33.0%; number needed to treat (NNT) = 3.0). SJZT was significantly more likely to reduce overall BSS score (SMD –0.67; 95% CI –0.94, –0.40; P < 0.00001) and improve abdominal pain (RR 4.34; 95% CI 2.64, 7.14; P < 0.00001) than placebo. The adverse events of SJZT were no different from those of placebo.

Conclusions

This meta-analysis suggests that SJZT is an effective and safe therapy option for patients with IBS-D. However, due to the high clinical heterogeneity and small sample size of the included trials, further standardized preparation, large-scale and rigorously designed trials are needed.     

The Effect of Disease Modifying Therapies on Brain Atrophy in Patients with Relapsing-Remitting Multiple Sclerosis: A Systematic Review and Meta-Analysis

Background

The aim of the present meta-analysis was to evaluate the effect of disease-modifying drugs (DMD) on brain atrophy in patients with relapsing-remitting multiple sclerosis (RRMS) using available randomized-controlled trial (RCT) data.

Methods

We conducted a systematic review and meta-analysis according to PRISMA guidelines of all available RCTs of patients with RRMS that reported data on brain volume measurements during the study period.

Results

We identified 4 eligible studies, including a total of 1819 RRMS patients (71% women, mean age 36.5 years, mean baseline EDSS-score: 2.4). The mean percentage change in brain volume was found to be significantly lower in DMD versus placebo subgroup (standardized mean difference: -0.19; 95%CI: -0.27–-0.11; p<0.001). We detected no evidence of heterogeneity between estimates (I² = 30%, p = 0.19) nor publication bias in the Funnel plots. Sensitivity analyses stratifying studies according to brain atrophy neuroimaging protocol disclosed no evidence of heterogeneity (p = 0.16). In meta-regression analyses, the percentage change in brain volume was found to be inversely related with duration of observation period in both DMD (meta-regression slope = -0.03; 95% CI: -0.04–-0.02; p<0.001) and placebo subgroups (meta-regression slope = -0.05; 95% CI: -0.06–-0.04; p<0.001). However, the rate of percentage brain volume loss over time was greater in placebo than in DMD subgroup (p = 0.017, ANCOVA).

Conclusions

DMD appear to be effective in attenuating brain atrophy in comparison to placebo and their benefit in delaying the rate of brain volume loss increases linearly with longer treatment duration.     

Effects of Fentanyl on Emergence Agitation in Children under Sevoflurane Anesthesia: Meta-Analysis of Randomized Controlled Trials

Background and Objectives

The goal of this meta-analysis study was to assess the effects of fentanyl on emergence agitation (EA) under sevoflurane anesthesia in children.

Subjects and Methods

We searched electronic databases (PubMed, Embase, Web of Science and the Cochrane Central Register of Controlled Trials) for articles published until December 2014. Randomized controlled trials (RCTs) that assessed the effects of fentanyl and placebo on EA under sevoflurane anesthesia in children that the outcome were the incidence of EA, postoperative pain, emergence time or adverse effects were included in this meta-analysis.

Results

A total of 16 studies, including 1362 patients (737 patients for the fentanyl group and 625 for the placebo group), were evaluated in final analysis. We found that administration of fentanyl decreased the incidences of EA (RR = 0.37, 95% CI 0.27~0.49, P<0.00001) and postoperative pain (RR = 0.59, 95% CI 0.41~0.85, P = 0.004) but increased the incidence of postoperative nausea and vomiting (PONV) (RR = 2.23, 95% CI 1.33~3.77, P = 0.003). The extubation time (WMD = 0.71 min, 95% CI 0.12~1.3, P = 0.02), emergence time (WMD = 4.90 min, 95% CI 2.49~7.30, P<0.0001), and time in the postanesthesia care unit (PACU) (WMD = 2.65 min, 95% CI 0.76~4.53, P = 0.006) were slightly increased. There were no significant differences in the time to discharge of day patients (WMD = 3.72 min, 95% CI -2.80~10.24, P = 0.26).

Conclusion

Our meta-analysis suggests that fentanyl decreases the incidence of EA under sevoflurane anesthesia in children and postoperative pain, but has a higher incidence of PONV. Considering the inherent limitations of the included studies, more RCTs with extensive follow-up should be performed to validate our findings in the future.     

Protein Diet Restriction Slows Chronic Kidney Disease Progression in Non-Diabetic and in Type 1 Diabetic Patients,but Not in Type 2 Diabetic Patients: A Meta-Analysis of Randomized Controlled Trials Using Glomerular Filtration Rate as a Surrogate

Background/ Objective

Studies, including various meta-analyses, on the effect of Protein Diet Restriction on Glomerular Filtration Rate (GFR) in Chronic Kidney Disease (CKD) have reported conflicting results. In this paper, we have provided an update on the evidence available on this topic. We have investigated the reasons why the effect has been inconsistent across studies. We have also compared the effect on GFR in various subgroups including type 1 diabetics, type 2 diabetics and non-diabetics.

Method

We searched for Randomized Controlled Trials on this intervention from MEDLINE, EMBASE, and other information sources. The PRISMA guidelines, as well as recommended meta-analysis practices were followed in the selection process, analysis and reporting of our findings. The effect estimate used was the change in mean GFR. Heterogeneity across the considered studies was explored using both subgroup analyses and meta-regression. Quality assessment was done using the Cochrane risk of bias tool and sensitivity analyses.

Results

15 randomized controlled trials, including 1965 subjects, were analyzed. The pooled effect size, as assessed using random-effects model, for all the 15 studies was -0.95 ml/min/1.73m²/year (95% CI: -1.79, -0.11), with a significant p value of 0.03. The combined effect estimate for the non-diabetic and type 1 diabetic studies was -1.50 ml/min/1.73m²/year (95% CI: -2.73, -0.26) with p value of 0.02. The effect estimate for the type 2 diabetic group was -0.17 ml/min/1.73m²/year (95% CI: -1.88, 1.55) with p value of 0.85. There was significant heterogeneity across the included studies (I² = 74%, p value for Q < 0.0001), explained by major variations in the percentage of type 2 diabetic subjects, the number of subjects and overall compliance level to diet prescribed.

Conclusion

Our findings suggest that protein diet restriction slows chronic renal disease progression in non-diabetic and in type 1 diabetic patients, but not in type 2 diabetic patients.     

Rituximab Effectiveness and Safety for Treating Primary Sj?gren’s Syndrome (pSS): Systematic Review and Meta-Analysis

Background

Primary Sjögren’s Syndrome (pSS) is a systemic autoimmune disease that involves the exocrine glands and internal organs. pSS leads to destruction and loss of secretory function due to intense lymphoplasmacytic infiltration. Therapeutic options include mainly symptomatic and supportive measures, and traditional immunosuppressant drugs have shown no effectiveness in randomized trials. Rituximab (RTX) is a chimeric antibody anti-CD20 that leads to B cell depletion by diverse mechanisms. There is evidence that this drug may be effective for treating pSS. The objective of this systematic review was to evaluate Rituximab effectiveness and safety for treating pSS.

Methods and Findings

We conducted a systematic review of RCTs published until December 2015, with no language restriction. We registered a protocol on Plataforma Brasil (40654814.6.0000.5505) and developed search strategies for the following scientific databases: MEDLINE, EMBASE, CENTRAL and LILACS. We included adults with established pSS diagnosis and considered the use of Rituximab as intervention and the use of other drugs or placebo as control. Four studies met our eligibility criteria: three with low risk of bias and one with uncertain risk of bias. The total number of participants was 276 (145 RTX, 131 placebo). We assessed the risk of bias of each included study and evaluated the following as primary outcomes: lacrimal gland function, salivary gland function, fatigue improvement and adverse events. We found no significant differences between the groups in the Schirmer test at week 24 meta-analysis (MD 3.59, 95% CI -2.89 to 10.07). Only one study evaluated the lissamine green test and reported a statistically significant difference between the groups at week 24 (MD -2.00, 95% CI -3.52 to -0.48). There was a significant difference between the groups regarding salivary flow rate (MD 0.09, 95% CI 0.02 to 0.16) and improvement in fatigue VAS at weeks 6 (RR 3.98, 95% CI 1.61 to 9.82) and week 16 (RR 3.08, 95% CI 1.21 to 7.80).

Conclusions

According to moderate quality evidence, the treatment with a single RTX course in patients with SSp presents discrete effect for improving lacrimal gland function. Low-quality evidence indicates the potential of this drug for improving salivary flow. According to low quality evidence, no differences were observed in the evaluation after 24 weeks regarding fatigue reduction (30% VAS), serious adverse events occurrence, quality of life improvement and disease activity. With a very low level of evidence, there was no improvement in oral dryness VAS evaluation.     

Effect of Intracuff Lidocaine on Postoperative Sore Throat and the Emergence Phenomenon: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background

Postoperative sore throat and other airway morbidities are common and troublesome after endotracheal tube intubation general anesthesia (ETGA). We propose lidocaine as endotracheal tube (ETT) cuff inflation media to reduce the postintubation-related emergence phenomenon.

Methods

We searched PubMed, EMBASE, and Cochrane databases systematically for randomized controlled trials (RCTs) that have investigated the outcome of intracuff lidocaine versus air or saline in patients receiving ETGA. Using a random-effects model, we conducted a meta-analysis to assess the relative risks (RRs) and mean difference (MD) of the incidence and intensity of relevant adverse outcomes.

Results

We reviewed nineteen trials, which comprised 1566 patients. The incidence of early- and late-phase postoperative sore throat (POST), coughing, agitation, hoarseness, and dysphonia decreased significantly in lidocaine groups, with RRs of 0.46 (95% confidence interval [CI]: 0.31 to 0.68), 0.41 (95% CI: 0.25 to 0.66), 0.43 (95% CI: 0.31 to 0.62), 0.37 (95% CI: 0.25 to 0.55), 0.43 (95% CI: 0.29 to 0.63), and 0.19 (95% CI: 0.08 to 0.5), respectively, when compared with the control groups. The severity of POST also reduced significantly (mean difference [MD] -16.43 mm, 95% CI: -21.48 to -11.38) at 1 h and (MD -10.22 mm, 95% CI: -13.5 to -6.94) at 24 h. Both alkalinized and non-alkalinized lidocaine in the subgroup analyses showed significant benefits in emergence phenomena prevention compared with the control.

Conclusion

Our results indicate that both alkalinized and non-alkalinized intracuff lidocaine may prevent and alleviate POST and postintubation-related emergence phenomena.     

Calcium Acetate or Calcium Carbonate for Hyperphosphatemia of Hemodialysis Patients: A Meta-Analysis

Background

High levels of serum phosphorus both at baseline and during follow-up are associated with increased mortality in dialysis patients, and administration of phosphate binders was independently associated with improved survival among hemodialysis population. Calcium-based phosphate binders are the most commonly used phosphate binders in developing countries for their relatively low costs.

Objectives

To compare the efficacy and safety between calcium carbonate and calcium acetate in the treatment of hyperphosphatemia in hemodialysis patients.

Methods

PubMed, EMBASE, Cochrane Library, Google scholar and Chinese databases (Wanfang, Weipu, National Knowledge Infrastructure of China) were searched for relevant studies published before March 2014. Reference lists of nephrology textbooks and review articles were checked. A meta-analysis of randomized controlled trials (RCTs) and quasi-RCTs that assessed the effects and adverse events of calcium acetate and calcium carbonate in adult patients with MHD was performed using Review Manager 5.0.

Results

A total of ten studies (625 participants) were included in this meta-analysis. There was insufficient data in all-cause mortality and cardiovascular events for meta-analysis. Compared with calcium carbonate group, the serum phosphorus was significantly lower in calcium acetate group after4 weeks’ administration (MD -0.15 mmol/L, 95% CI -0.28 to -0.01) and after 8 weeks’ administration (MD -0.25 mmol/L, 95% CI -0.40 to -0.11). There was no difference in serum calcium levels or the incidence of hypercalcemia between two groups at 4 weeks and 8 weeks. No statistical difference was found in parathyroid hormone (PTH) levels or serum calcium by phosphorus (Ca x P) product. There was significantly higher risk of intolerance with calcium acetate treatment (RR 3.46, 95% CI 1.48 to 8.26).

Conclusions

For hyperphosphatemia treatment, calcium acetate showed better efficacy and with a higher incidence of intolerance compared with calcium carbonate. There are insufficient data to establish the comparative superiority of the two calcium-based phosphate binders on all-cause mortality and cardiovascular end-points in hemodialysis patients.     

Steroid Avoidance or Withdrawal Regimens in Paediatric Kidney Transplantation: A Meta-Analysis of Randomised Controlled Trials

Background

We combined the outcomes of all randomised controlled trials to investigate the safety and efficacy of steroid avoidance or withdrawal (SAW) regimens in paediatric kidney transplantation compared with steroid-based (SB) regimens.

Methods

A systematic literature search of PubMed, Embase, Cochrane Library, the trials registry and BIOSIS previews was performed. A change in the height standardised Z-score from baseline (ΔHSDS) and acute rejection were the primary endpoints.

Results

Eight reports from 5 randomised controlled trials were included, with a total of 528 patients. Sufficient evidence of a significant increase in the ΔHSDS was observed in the SAW group (mean difference (MD) = 0.38, 95% confidence interval (CI) 0.07–0.68, P = 0.01), particularly within the first year post-withdrawal (MD = 0.22, 95% CI 0.10–0.35, P = 0.0003) and in the prepubertal recipients (MD = 0.60, 95% CI 0.21–0.98, P = 0.002). There was no significant difference in the risk of acute rejection between the groups (relative risk = 1.04, 95% CI 0.80–1.36, P = 0.77).

Conclusions

The SAW regimen is justified in select paediatric renal allograft recipients because it provides significant benefits in post-transplant growth within the first year post-withdrawal with minimal effects on the risk of acute rejection, graft function, and graft and patient survival within 3 years post-withdrawal. These select paediatric recipients should have the following characteristics: prepubertal; Caucasian; with primary disease not related to immunological factors; de novo kidney transplant recipient; with low panel reactive antibody.     

Cardiovascular Outcomes of Sitagliptin in Type 2 Diabetic Patients with Acute Myocardial Infarction,a Population-Based Cohort Study in Taiwan

Background

The cardiovascular safety and efficacy of sitagliptin, a dipeptidyl peptidase 4 (DPP-4) inhibitor, in type 2 diabetic patients after acute myocardial infarction (AMI) has so far remained uncertain.

Methods

We analyzed data from the National Health Insurance Research Database (NHIRD), a government-operated, population-based database, from March 1st, 2009 to December 31st, 2011. Type 2 diabetic patients hospitalized for AMI were included in our study. We compared subjects using sitagliptin with comparison group to evaluate its cardiovascular safety and efficacy. The primary endpoint was a composite of cardiovascular death, myocardial infarction, and ischemic stroke.

Results

We identified a total of 3,282 type 2 diabetic patients hospitalized for AMI (mean follow-up 1.15 years). Of these patients, 547 (16.7%) who were exposed to sitagliptin were defined as the sitagliptin group and 2,735 (83.3 %) who did not use sitagliptin were the comparison group. The incidence of primary composite cardiovascular outcomes was 9.50 per 100 person-years in the sitagliptin group and was 9.70 per 100 person-years in the comparison group (hazard ratio (HR), 0.97; 95% CI, 0.73–1.29, P=0.849). Compared to the non-sitagliptin group, the sitagliptin group had similar risks of all-cause mortality, hospitalization for heart failure (HF) or percutaneous coronary intervention (PCI) with a HR of 0.82 (95% CI, 0.61–1.11, P=0.195), 0.93 (95% CI, 0.67–1.29, P=0.660), and 0.93 (95% CI, 0.75–1.14, P=0.473), respectively.

Conclusion

The use of sitagliptin in type 2 diabetic patients with recent AMI was not associated with increased risk of adverse cardiovascular events.     

Inhaled Long-Acting β2-Agonists Do Not Increase Fatal Cardiovascular Adverse Events in COPD: A Meta-Analysis

Background

The cardiovascular safety of inhaled long-acting β₂-agonists (LABAs) in patients with chronic obstructive pulmonary disease (COPD) is a controversial problem. Certain studies have suggested that inhaled LABAs lead to an increased risk of cardiovascular events in patients with COPD. This meta-analysis aimed to assess the cardiovascular safety of inhaled LABAs in COPD.

Methods

A meta-analysis of randomized, double-blind, parallel-group, placebo-controlled trials for LABA treatment of COPD with at least 3 months of follow-up was performed. The fixed-effects model was used to evaluate the effects of LABAs on fatal cardiovascular adverse events. Adverse events were collected for each trial, and the relative risk (RR) and 95% confidence intervals (CI) for LABA/placebo were estimated.

Results

There were 24 trials included in this meta-analysis. Compared with placebo, inhaled LABAs significantly decreased fatal cardiovascular adverse events in COPD patients (RR 0.65, 95% CI 0.50 to 0.86, P = 0.002). In sensitivity analysis, there was still no increased risk of fatal cardiovascular events (RR 0.68, 95%CI 0.46 to 1.01, P = 0.06) after excluding the trial with the largest weight. Among the different types of LABAs, only salmeterol had a significant effect (RR 0.64, 95% CI 0.46 to 0.90). In subgroup analyses, inhaled LABAs were able to significantly decrease fatal cardiovascular events in long-term trials (RR 0.64, 95% CI 0.47 to 0.87) and in trials with severe COPD patients (RR 0.69, 95% CI 0.50 to 0.96).

Conclusion

Inhaled LABAs do not increase the risk of fatal cardiovascular events in COPD patients.     

Identifying Adult Dengue Patients at Low Risk for Clinically Significant Bleeding

Background

Clinically significant bleeding is important for subsequent optimal case management in dengue patients, but most studies have focused on dengue severity as an outcome. Our study objective was to identify differences in admission parameters between patients who developed clinically significant bleeding and those that did not. We sought to develop a model for discriminating between these patients.

Methods

We conducted a retrospective study of 4,383 adults aged >18 years who were hospitalized with dengue infection at Tan Tock Seng Hospital, Singapore from 2005 to 2008. Patients were divided into those with clinically significant bleeding (n = 188), and those without (n = 4,195). Demographic, clinical, and laboratory variables on admission were compared between groups to determine factors associated with clinically significant bleeding during hospitalization.

Results

On admission, female gender (p<0.001); temperature >38°C (p<0.001); nausea/vomiting (p = 0.009) and abdominal pain/tenderness (p = 0.005); lower systolic blood pressure (p<0.001); higher pulse rate (p<0.001); increased absolute neutrophil count (ANC; p<0.001); reduced absolute lymphocyte count (ALC; p<0.001), haematocrit percentage (p<0.001) and platelet count (p = 0.04), and increased prothrombin time (p = 0.003) were significantly associated with clinically significant bleeding on univariate analysis. Multivariate analysis showed that independent variables in the final model were female gender (aOR 2.85; 95% CI: 1.9–4.33); temperature >38°C (aOR 1.81; 95% CI: 1.27–2.61), nausea/vomiting (aOR 1.39; 95% CI: 0.94–2.12), ANC (aOR 1.3; 95% CI: 1.15–1.46), ALC (aOR 0.4; 95% CI: 0.25–0.64), hematocrit percentage (aOR 0.96; 95% CI: 0.92–1.002) and platelet count (aOR 0.993; 95% CI: 0.988–0.998). At the cutoff of -3.919, the model achieved an AUC of 0.758 (sensitivity:0.87, specificity: 0.38, PPV: 0.06, NPV: 0.98).

Conclusion

Clinical risk factors associated with clinically significant bleeding were identified. This model may be useful to complement clinical judgement in triaging adult dengue patients given the dynamic nature of acute dengue, particularly in pre-identifying those less likely to develop clinically significant bleeding.     

Prognostic Value of Circulating Tumor Cells in Ovarian Cancer: A Meta-Analysis

Background

The prognostic value of circulating tumor cells (CTCs) in ovarian cancer has been investigated in previous studies, but the results are controversial. Therefore we performed a meta-analysis to systematically review these data and evaluate the value of CTCs in ovarian cancer.

Materials and Methods

A literary search for relevant studies was performed on Embase, Medline and Web of Science databases. Then pooled hazard ratios (HRs) for survival with 95% confidence intervals (CIs), subgroup analyses, sensitivity analyses, meta-regression analyses and publication bias were conducted.

Results

This meta-analysis is based on 11 publications and comprises a total of 1129 patients. The prognostic value of the CTC status was significant in overall survival (OS) (HR, 1.61;95% CI,1.22–2.13) and progression-free survival (PFS)/disease-free survival (DFS) (HR, 1.44; 95%CI, 1.18–1.75). Furthermore, subgroup analysis revealed that the value of CTC status in OS was significant in "RT-PCR" subgroup (HR, 2.02; 95% CI, 1.34–3.03), whereas it was not significant in "CellSearch" subgroup (HR, 1.15; 95% CI 0.45–2.92) and "other ICC" subgroup (HR, 1.09; 95% CI 0.62–1.90). The presence of CTC was also associated with an increased CA-125 (OR, 4.07; 95%CI, 1.87–8.85).

Conclusion

Our study demonstrates that CTC status is associated with OS and PFS/DFS in ovarian cancer.     

Norwegian PUQE (Pregnancy-Unique Quantification of Emesis and Nausea) Identifies Patients with Hyperemesis Gravidarum and Poor Nutritional Intake: A Prospective Cohort Validation Study

Objective

The English questionnaire Pregnancy-Unique Quantification of Emesis and nausea (PUQE) identifies women with severe Hyperemesis Gravidarum. Our aim was to investigate whether scores from the translated Norwegian version; SUKK (SvangerskapsUtløst Kvalme Kvantifisering) was associated with severity of hyperemesis and nutritional intake.

Design

A prospective cohort validation study.

Setting

Hospital cohort of Hyperemesis Gravidarum (HG) patients from western Norway and healthy pregnant women from Bergen, Norway.

Sample

38 women hospitalized due to HG and 31 healthy pregnant controls attending routine antenatal check-up at health centers.

Methods

Data were collected May 2013-January 2014. The study participants answered the Norwegian PUQE-questionnaire (scores ranging from 3 to15) and registered prospectively 24-hours nutritional intake by a food list form.

Main outcome measures

Differences of PUQE-scores, QOL-score and nutritional intake between hyperemesis patients and controls.

Results

Hyperemesis patients had shorter gestational age compared to controls (median 9.7 weeks; 95% CI 8.6-10.6 versus 11.9; 95% CI 10.1-12.9, p=0.004), and larger weight-change from pre-pregnant weight (loss of median 3 kg; 95% CI 3-4 versus gain of 2 kg; 95% CI 0.5-2, p<0.001) otherwise groups were similar regarding pre-pregnant BMI, age, gravidity, and inclusion weight. Compared to controls, hyperemesis patients had significant higher PUQE-score (median 13; 95% CI 11-14 vs. 7; 95% CI 4-8), lower QOL (median score 3; 95% CI 2-4 vs. 6; 95% CI 4.5-8) and lower nutritional intake (energy intake median 990 kcal/24 hours; 95% CI 709-1233 vs. 1652; 95% CI 1558-1880 all p<0.001). PUQE-score was inversely correlated to nutritional intake (-0.5, p<0.001). At discharge PUQE-score had fallen to median 6 (95% CI 5-8) and QOL score risen to 7 (95% CI 6-8) in the HG group, (both p<0.001 compared to admission values).

Conclusion

PUQE-scoring has been validated as a robust indicator of severe hyperemesis gravidarum and insufficient nutritional intake in a Norwegian setting.     

The Dose-Dependent Effect of Nesiritide on Renal Function in Patients with Acute Decompensated Heart Failure: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background

Conflicting renal effects of nesiritide have been reported in patients with acute decompensated heart failure. To answer this controversy, we performed a meta-analysis of randomized controlled trials to evaluate the influence of nesiritide on renal function in patients with acute decompensated heart failure.

Methods

Articles were obtained from PubMed, Medline, Cochrane Library and reference review. Randomized controlled studies that investigated the effects of continuous infusion of nesiritide on renal function in adult patients with acute decompensated heart failure were included and analyzed. Fixed-effect model was used to estimate relative risk (RR) and weight mean difference (WMD). The quality assessment of each study, subgroup, sensitivity, and publication bias analyses were performed.

Results

Fifteen randomized controlled trials were eligible for inclusion. Most of included studies had relatively high quality and no publication bias was found. Overall, compared to control therapies, nesiritide might increase the risk of worsening renal function in patients with acute decompensated heart failure (RR 1.08, 95% CI 1.01–1.15, P = 0.023). In subgroup analysis, high-dose nesiritide strongly associated with renal dysfunction (RR 1.54, 95% CI 1.19-2.00, P = 0.001), but no statistical differences were observed in standard-dose (RR 1.04, 95% CI 0.98-1.12, P = 0.213), low-dose groups (RR 1.01, 95% CI 0.74-1.37, P = 0.968) and same results were identified in the subgroup analysis of placebo controlled trials. Peak mean change of serum creatinine from baseline was no significant difference (WMD -2.54, 95% CI -5.76-0.67, P = 0.121).

Conclusions

In our meta-analysis, nesiritide may have a dose-dependent effect on renal function in patients with acute decompensated heart failure. High-dose nesiritide is likely to increase the risk of worsening renal function, but standard-dose and low-dose nesiritide probably have no impact on renal function. These findings could be helpful to optimize the use of nesiritide in clinical practice.     

Type 2 Diabetes Mellitus and Kidney Cancer Risk: A Retrospective Cohort Analysis of the National Health Insurance

Purpose

To evaluate the association between incidence of any kidney cancer and type 2 diabetes mellitus.

Methods

A random sample of 1,000,000 subjects covered by the National Health Insurance was recruited. A total of 998728 people (115655 diabetes and 883073 non-diabetes) without kidney cancer at recruitment were followed from 2003 to 2005. The cumulative incidence of kidney cancer from 2003 to 2005 in diabetic patients and non-diabetic people in all ages and in age <40, 40–64, 65–74 and ≥75 years were calculated in the diabetic patients and the non-diabetic people, respectively. Logistic regression was used to estimate the odds ratios comparing diabetic patients to non-diabetic people in the respective age groups. Multivariable-adjusted odds ratios for kidney cancer with regards to diabetes status and diabetes duration (as a continuous variable or categorized into subgroups of non-diabetes, diabetes duration <1 year, 1–2.9 years, 3–4.9 years and ≥5 years) were estimated after multivariable adjustment. The multivariable-adjusted odds ratios for all baseline variables were also estimated for diabetic patients and non-diabetic people, respectively.

Results

The 3-year cumulative incidence of kidney cancer in the diabetic patients and the non-diabetic people was 166.9 and 33.1 per 100,000 person-years, respectively. The incidence increased with regards to increasing age in both the diabetic patients and the non-diabetic people, but a higher risk of kidney cancer for the diabetic patients compared to the non-diabetic people was consistently observed in different age groups. After multivariable adjustment, the odds ratio for diabetic patients versus non-diabetic people was 1.7 (95% confidence interval: 1.3–2.1, P<0.01). While compared to the non-diabetic people, the odds ratio (95% confidence interval) for diabetes duration <1, 1–2.9 years, 3–4.9 years and ≥5 years was 1.5 (0.8–2.7), 1.6 (1.0–2.4), 1.6 (1.1–2.4) and 1.7 (1.3–2.3), respectively (P-trend <0.01). Analyses conducted in the diabetic patients and the non-diabetic people, respectively, consistently showed age, nephropathy and end-stage renal disease as significant risk factors of kidney cancer. Additionally, living in metropolitan Taipei region might also be associated with a higher risk of kidney cancer in the non-diabetic people, indicating a potential link between kidney cancer and some factors related to urbanization.

Conclusions

Patients with type 2 diabetes mellitus have a significantly higher risk of kidney cancer.     

Intra-Articular Corticosteroids in Addition to Exercise for Reducing Pain Sensitivity in Knee Osteoarthritis: Exploratory Outcome from a Randomized Controlled Trial

Objective

To assess the effects of one intra-articular corticosteroid injection two weeks prior to an exercise-based intervention program for reducing pain sensitivity in patients with knee osteoarthritis (OA).

Design

Randomized, masked, parallel, placebo-controlled trial involving 100 participants with clinical and radiographic knee OA that were randomized to one intra-articular injection on the knee with either 1 ml of 40 mg/ml methylprednisolone (corticosteroid) dissolved in 4 ml lidocaine (10 mg/ml) or 1 ml isotonic saline (placebo) mixed with 4 ml lidocaine (10 mg/ml). Two weeks after the injections all participants undertook a 12-week supervised exercise program. Main outcomes were changes from baseline in pressure-pain sensitivity (pressure-pain threshold [PPT] and temporal summation [TS]) assessed using cuff pressure algometry on the calf. These were exploratory outcomes from a randomized controlled trial.

Results

A total of 100 patients were randomized to receive either corticosteroid (n = 50) or placebo (n = 50); 45 and 44, respectively, completed the trial. Four participants had missing values for PPT and one for TS at baseline; thus modified intention-to-treat populations were analyzed. The mean group difference in changes from baseline at week 14 was 0.6 kPa (95% CI: -1.7 to 2.8; P = 0.626) for PPT and 384 mm×sec (95% CI: -2980 to 3750; P = 0.821) for TS.

Conclusions

These results suggest that adding intra-articular corticosteroid injection 2 weeks prior to an exercise program does not provide additional benefits compared to placebo in reducing pain sensitivity in patients with knee OA.

Trial Registration

EU clinical trials (EudraCT): 2012-002607-18     

Effect of Prophylactic Low Level Laser Therapy on Oral Mucositis: A Systematic Review and Meta-Analysis

Background

Objective was to determine whether prophylactic low level laser therapy (LLLT) reduces the risk of severe mucositis as compared to placebo or no therapy.

Methods

MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials were searched until February 2014 for randomized controlled trials (RCTs) comparing prophylactic LLLT with placebo or no therapy in patients with cancer or undergoing hematopoietic stem cell transplantation (HSCT). All analyses used random effects models.

Results

Eighteen RCTs (1144 patients) were included. Prophylactic LLLT reduced the overall risk of severe mucositis (risk ratio (RR) 0.37, 95% confidence interval (CI) 0.20 to 0.67; P = 0.001). LLLT also reduced the following outcomes when compared to placebo/no therapy: severe mucositis at the time of anticipated maximal mucositis (RR 0.34, 95% CI 0.20 to 0.59), overall mean grade of mucositis (standardized mean difference −1.49, 95% CI −2.02 to −0.95), duration of severe mucositis (weighted mean difference −5.32, 95% CI −9.45 to −1.19) and incidence of severe pain (RR 0.26, 95% CI 0.18 to 0.37).

Conclusion

Prophylactic LLLT reduced severe mucositis and pain in patients with cancer and HSCT recipients. Future research should identify the optimal characteristics of LLLT and determine feasibility in the clinical setting.