The influence of post-rewarming temperature management on post-rewarming fever development after cardiac arrest

Aim of the studyWe evaluated the influence of post-rewarming temperature management (PRTM) on post-rewarming fever development and determined the association between the temperature in the immediate post-targeted temperature management (TTM) period and outcomes.MethodsThis retrospective observational study included consecutive adult cardiac arrest survivors treated with TTM from January 2008 to December 2013. Beginning in August 2010, our institution implemented a PRTM protocol involving continued use of temperature management device to maintain normothermia during the first 24 h after rewarming. The outcomes were in-hospital mortality and neurologic outcome at discharge. We evaluated the effect on clinical outcomes of post-rewarming fever defined at a temperature over 38 °C within 48 h after rewarming.ResultsOf 277 included patients, 55.2% underwent PRTM. The incidence of post-rewarming fever did not differ between the PRTM and no-PRTM groups (odds ratio [OR] 0.963, confidence interval [CI] 0.519, 1.787). Post-rewarming fever was associated with decreased in-hospital mortality (OR 0.243, CI 0.110, 0.534) and decreased rate of unfavorable neurologic outcome (OR 0.312, CI 0.182, 0.534). During 48 h following rewarming, mean temperature was 36.5 °C (36.2–36.8 °C), and peak temperature was 37.5 °C (36.8–38.1 °C). On multivariate analyses, lower mean temperature was associated with increased in-hospital mortality (OR 0.099, CI 0.037, 0.262) and unfavorable neurologic outcome (OR 0.071, CI 0.026, 0.193).ConclusionIt appeared that PRTM did not prevent post-rewarming fever development. Post-rewarming fever was associated with favorable outcomes while lower body temperature after rewarming was associated with unfavorable outcomes. Our results require further confirmation by larger prospective studies.     

Early targeted brain COOLing in the cardiac CATHeterisation laboratory following cardiac arrest (COOLCATH)

IntroductionTrials demonstrate significant clinical benefit in patients receiving therapeutic hypothermia (TH) after cardiac arrest. However, incidence of mortality and morbidity remains high in this patient group. Rapid targeted brain hypothermia induction, together with prompt correction of the underlying cause may improve outcomes in these patients. This study investigates the efficacy of Rhinochill^®, an intranasal cooling device over Blanketrol^®, a surface cooling device in inducing TH in cardiac arrest patients within the cardiac catheter laboratory.Methods70 patients were randomized to TH induction with either Rhinochill^® or Blanketrol^®. Primary outcome measures were time to reach tympanic ≤34 °C from randomisation as a surrogate for brain temperature and oesophageal ≤34 °C from randomisation as a measurement of core body temperature. Secondary outcomes included first hour temperature drop, length of stay in intensive care unit, hospital stay, neurological recovery and all-cause mortality at hospital discharge.ResultsThere was no difference in time to reach ≤34 °C between Rhinochill^® and Blanketrol^® (Tympanic ≤34 °C, 75 vs. 107 mins; p = 0.101; Oesophageal ≤34 °C, 85 vs. 115 mins; p = 0.151). Tympanic temperature dropped significantly with Rhinochill^® in the first hour (1.75 vs. 0.94 °C; p < 0.001). No difference was detected in any other secondary outcome measures. Catheter laboratory-based TH induction resulted in a survival to hospital discharge of 67.1%.ConclusionIn this study, Rhinochill^® was not found to be more efficient than Blanketrol^® for TH induction, although there was a non-significant trend in favour of Rhinochill^® that potentially warrants further investigation with a larger trial.     

Assessment of aquo-ethanolic extract of Camellia sinensis against Carbapenem Resistant Escherichia coli: In Vivo Trials in a Murine Model

The prevalence of Carbapenem Resistant Escherichia coli (CRE) has increased considerably during the last decade, which can be ascribed to relative scarcity of effective non toxic antimicrobial agents. The present study was conducted to evaluate the antimicrobial activity of aquo-ethanolic (1:1) extract of leaves of Camellia sinensis (PTRC-31911-A) against Carbapenem Resistant Escherichia coli at preclinical level using peritonitis infection model in Sprague Dawley rats. Efficacy analysis of PTRC-31911-A involved enumeration of CRE colonies in blood and urine samples of test animals for a period of 5 days from infection. A reduction in microbial count of biological fluids was considered as the primary endpoint of the selected murine model. Physical, biochemical, hematological and histological indices of toxicity were employed as secondary relative indicators of the induced disease. Physical manifestations of infected rats included significantly high body temperature (Temp_Infected = 103.18 °F, ∼5% increase) and noteworthy reduction in weight (Weight_Infected = 126.83 g, ∼15% decrease) as compared to control. Significant (P < 0.05) increase in total white blood cells, eosinophil and monocyte counts as well as a significant decrease (P < 0.05) in erythrocytes count, hematocrit volume, red blood cell distribution width and hemoglobin concentration were observed in the infected group as compared to the control group. Furthermore, noteworthy increase in liver and kidney function test parameters were observed in case of infected groups. All the hematological and biochemical parameters were found to be within optimum range in case of treatment group, indicating restoration of homeostasis. Histopathological studies also presented symptoms of hemorrhage and glomerular damage with structural distortion in glomerular capillary loops of infected groups, which were later recovered in treated groups, indicating the nephro-protective potential of PTRC-31911-A. The study clearly points out that Camellia sinensis extract (PTRC-31911-A; single dose of 5 mg/Kg bwt; oral, + 24 h) is highly effective against Carbapenem Resistant Escherichia coli owing mainly to the presence of flavonoids and polyphenolic compounds, identified by LCMS. Ongoing studies are expected to further unravel the mechanism of action and bioactivity determinants of this broad spectrum plant extract.     

Qi deficiency is associated with depression in chronic hemodialysis patients

ObjectiveDepression is a common bio-psycho-social problem in hemodialysis (HD) patients. Traditional Chinese medicine has been used for symptom management in patients with depression. Identification of the specific constitution in traditional Chinese medicine is critical for personalized care. However, the association between depression and specific constitution in HD patients is unknown.MethodsWe conducted a cross-sectional study in all chronic HD patients (HD for more than 3 months) at China Medical University Hospital in Taiwan. The depression symptom severity was determined using the Beck Depression Inventory II (BDI-II). Clinical patterns in Chinese medicine were determined using the Constitution in Chinese Medicine Questionnaire. The association between constitution and depression was analyzed using logistic regression.ResultsWe recruited 467 chronic hemodialysis patients, including 219 females and 248 males, with a mean age of 63 ± 12 years. The mean duration of HD was 5.8 years. The mean score for the BDI-II was 11 (interquartile range 8–14). The major constitution was Yang-deficiency (43.7%) among these chronic HD patients. Qi-deficiency was correlated with a duration of HD of more than 5.8 years (p = 0.04). Qi-deficiency [odds ratio (OR): 4.05, 95% confidence interval (CI): 1.69–9.72, p < 0.01] was also associated with depression in logistic regression with adjustments for confounders, including calcium, phosphorus and hemoglobin levels.ConclusionQi-deficiency constitution in Chinese medicine is associated with depression in chronic HD patients. Further studies are needed to determine whether treating Qi-deficiency integrating Chinese medicine treatment can improve patients’ depression symptoms.     

Outcome and risk factors in children after traumatic cardiac arrest and successful resuscitation

IntroductionProspective collected data of the TraumaRegister DGU^® were analyzed to derive survival rates and predictors for non-survival in the children who had suffered traumatic cardiorespiratory arrest. Different time points of resuscitation efforts (only preclinical, in the emergency room (ER) or preclinical + ER) were analyzed in terms of mortality and neurological outcome.MethodsThe database of the TraumaRegister DGU^® comprising 122,742 patients from 1993 to 2013 was analyzed. The main focus of this survey was on the paediatric group defined by an age ≤14 years who could be compared to adults. Different statistical analysis (univariate and multivariate analysis, logistic regression) were performed with mortality as the target variable. Differences between the paedatric group and adults were analysed by Fisher's exact test.ResultsData after preclinical and/or ER resuscitation from 152 children and 1690 adults were analyzed. A good or moderate outcome (GOS 5 + 4) was found in 19.4% of the children's group compared to 12.4% of the adults (p = 0.02).Analysis of the GOS 5 + 4 subgroups after preclinical resuscitation only revealed that these outcomes were achieved by 19.4% of the paediatric group and 13.2% of the adults (p = 0.24), after ER-only resuscitation by 37.0% of the children and 19.6% of the adults (p = 0.046), and after preclinical and ER resuscitation by only 10.9% of the children compared to 2.5% of the adults (p = 0.006). Taking only survivors into account, 84.8% of the children and 62% of the adults had a GOS 4 + 5.The highest risk for mortality in the logistic regression model was associated with preclinical intubation, followed by GCS 3, blood transfusion and severe head injury with AIS ≥3 and ISS.ConclusionsCPR in children after severe trauma seems to yield a better outcome than in adults, and appears to be more justified than the current guidelines would imply. Resuscitation in the ER is associated with better neurological outcomes compared with resuscitation in a preclinical context or in both the preclinical phase and the ER. Our children's outcomes seem to be better than those in most of the earlier studies, and the data presented might support algorithms in the future especially for paediatric resuscitation.     

Changes in treatments and outcomes among elderly patients with out-of-hospital cardiac arrest between 2002 and 2012: A post hoc analysis of the SOS-KANTO 2002 and 2012

BackgroundLittle is known about recent changes in pre- and in-hospital treatments and outcomes for elderly patients with out-of-hospital cardiac arrest (OHCA).MethodsWe compared data collected for the SOS-KANTO study in 2002 and 2012. We included patients aged ≥65 years who experienced OHCA of cardiac aetiology. The primary endpoint was favourable neurological outcomes 1 month after cardiac arrest.ResultsA total of 8,964 (2002 vs. 2012: 3,544 vs. 5,420) patients were eligible for the current analysis. The proportion of pre-hospital return of spontaneous circulation (ROSC) increased significantly (3.8 vs. 5.6%, p < 0.001). Among patients achieving ROSC, the proportion of advanced in-hospital treatments (i.e. extracorporeal membrane oxygenation, therapeutic hypothermia, and/or percutaneous coronary angiogram/intervention) provided increased significantly in 2012 (1.2 vs. 5.5%, p < 0.001; 2.6 vs. 15.1%, p < 0.001; 4.9 vs. 16.5%, p < 0.001; respectively). The proportion of favourable neurological outcomes at 1 month increased significantly in 2012 (1.6 vs. 2.7%, p = 0.001). A logistic regression analysis that did not consider advanced in-hospital treatments showed a significantly higher rate of favourable neurological outcomes in the 2012 group than that in the 2002 group (OR, 2.2; 95% CI, 1.4–3.5). However, this difference was no longer observed in the second regression model that accounted for advanced in-hospital treatments (OR, 1.6; 95% CI, 0.9–2.9).ConclusionThere was an increased proportion of aggressive treatment, both pre- and in-hospital, for elderly patients with cardiogenic OHCA in the Kanto area, Japan. Favourable neurological outcomes improved significantly over 10 years.     

Prognostic values of gray matter to white matter ratios on early brain computed tomography in adult comatose patients after out-of-hospital cardiac arrest of cardiac etiology

Aim of the studyPrevious studies found that the gray matter to white matter ratio (GWR) on brain computed tomography (CT) could be used to predict poor outcomes in cardiac arrest survivors. However, these studies have included cardiac arrests of both cardiac and non-cardiac etiologies. We sought to evaluate if the GWR on brain CT can help to predict poor outcomes after out-of-hospital cardiac arrest (OHCA) of cardiac etiology.MethodsUsing a multicenter retrospective registry of adult cardiac arrest survivors treated with therapeutic hypothermia, we identified survivors of OHCA of cardiac etiology who underwent brain CT within 24 h after successful resuscitation. Gray and white matter attenuations were measured, and the GWRs were calculated as in previous studies. The prognostic values of the GWRs were analyzed, and a logistic regression analysis was performed to determine the contribution of the GWR in predicting poor outcomes (Cerebral Performance Category 3–5).Resultsof 283 included patients, 140 had good outcomes and 143 had poor outcomes. Although the GWRs could predict poor outcomes with statistical significance, the sensitivities were remarkably low (3.5% to 5.6%) at cutoff values with 100% specificity. No significant difference in predictive performance was found between the primary predictive model, containing independent poor outcome predictors, and the primary predictive model combined with the GWR.ConclusionIn a cohort of comatose adults after OHCA of cardiac etiology, the GWR demonstrated poor predictive performance and was not helpful in predicting poor outcomes.     

Improved cisplatin delivery in cervical cancer cells by utilizing folate-grafted non-aggregated gelatin nanoparticles

PurposeCisplatin is highly effective in the treatment of cervical cancer. However, in therapeutic doses, cisplatin induces several adverse effects due to undesirable tissue distribution. Therefore, it is worth targeting cisplatin in cervical cancer cells by implicating non-aggregated ligand-modified nanotherapeutics.Methods and resultsHere, we report the preparation of non-aggregated folic acid-conjugated gelatin nanoparticles of cisplatin (Cis-GNs-FA) by two-step desolvation method with mean particle size of 210.6 ± 9.6 nm and 140.5 ± 10.9 nm for Cis-GNs to improve the drug delivery in cervical cancer, HeLa cells. FTIR and DSC spectra confirmed the presence and stability of cisplatin in gelatin matrix. Furthermore, amorphization of cisplatin in nanoparticles was ascertained by PXRD. Drug release followed a first-order release kinetic at both pH ∼ 5.6 (cervical cancer pH) and pH ∼ 7.4. In addition, a significant (P < 0.05) decrease in IC₅₀ value (8.3 μM) and enhanced apoptosis were observed in HeLa cells treated with Cis-GNs-FA as compared to Cis-GNs (15.1 μM) and cisplatin solution (40.2 μM). In contrast, A549 lung cancer cells did not discriminate between Cis-GNs-FA and Cis-GNs due to the absence of folate receptors-α (FR-α). Consistently, higher cellular uptake, 80.54 ± 7.60% was promoted by Cis-GNs-FA significantly (two-way ANOVA, P < 0.05) greater than 51.68 ± 9.78%, by Cis-GNs. This was also illustrated by CLSM images, which indicated that Cis-GNs-FA preferably accumulated in the cytoplasm of HeLa cells nearby nucleus by following receptor-mediated endocytosis pathway as compared to Cis-GNs.ConclusionTherefore, Cis-GNs-FA warrants further in-depth in vitro and in vivo investigations to scale up the technology for clinical translation.     

Antidiabetic,antihyperlipidemic and anti-inflammatory effects of tilianin in streptozotocin-nicotinamide diabetic rats

Flavonoids from medicinal plants have been used in traditional medicine to treat a variety of prevalent diseases. Flavones activate the signaling pathways promoting fuel metabolism and insulin sensitizing in hepatocytes and adipocytes, which suggests that flavones may have the potential to exert in vivo antidiabetic and antihyperlipidemic effects. Thus, the aim of the current study was to determine the antidiabetic, antihyperlipidemic and anti-inflammatory effects of tilianin in diabetic rats. Also, to understand the mechanism involved using in vitro 3T3-L1 cells and tissues from experimental animals treated with test samples through molecular profile studies.Non insulin-dependent diabetic mellitus (NIDDM) rats were treated over a short period (for 10 days) with 60 mg/Kg/day of tilianin. After treatment, a biochemical blood profile was determined. Also, adipose and thoracic aortic tissues were used to determine pro-inflammatory profile, adiponectin and adhesion molecules by real-time PCR. In 3T3-L1 cells pretreated with tilianin (10 μM), PPARα, PPARγ, GLUT4, FATP-1 and ACSL-1 mRNA expression were measured. In order to explain the potential PPARα interaction with tilianin, a docking study with PPARα was carried out. Thus, intragastric administration of tilianin and metformin induced a decrease in plasma glucose (GLU) in diabetic rats on day 6, and remained significantly lower until the end of the treatment; also blood triacylglycerides (TAG) and cholesterol (CHOL) (p < 0.05) were diminished. Moreover, IL-1β and IL-18 expression was significantly decreased in adipose tissue (p < 0.05); meanwhile adiponectin was significantly overexpressed (p < 0.05). Besides, ICAM-1 expression was significantly reduced in aortic tissue (p < 0.05). In 3T3-L1 cells it was found that tilianin increased PPARα and ACSL1 mRNA levels (p < 0.05). Finally, tilianin docking studies with PPARα showed polar interactions with Glu269, Tyr314, His 440 and Tyr464 residues. In conclusion, short-term tilianin treatment might exert its antidiabetic and antihyperlipidemic effect by modulating a pro-inflammatory profile, and increasing adiponectin expression. In addition, our results suggest the possible interaction of tilianin with PPARα.     

Stealth lipid coated aquasomes bearing recombinant human interferon-α-2b offered prolonged release and enhanced cytotoxicity in ovarian cancer cells

PurposeIn present investigation, recombinant human interferon-α-2b (rhINF-α-2b) loaded aquasomes were prepared, optimized and overlaid with PEGylated phospholipid to offer prolong release and high therapeutic index against ovarian cancer, SKOV3 cells.Methods and resultsCentral Composite Design (CCD) and Response Surface Methodology (RSM) were employed to calculate the optimized conditions, 1:3 core to coat ratio, sonication power of 12.5 W and time of about 55 min for preparation of aquasomes. Consequently, rhINF-α-2b-Py-5-P-Aq.somes exhibited higher protein loading capacity and retained structural conformations of rhINF-α-2b, as compared to rhINF-α-2b-Cellob-Aq.somes, rhINF-α-2b-Tre-Aq.somes and rhINF-α-2b-Core (CaHPO₄). Further, optimized rhINF-α-2b-Py-5-P-Aq.somes was superimposed with phospholipid-PEG₂₀₀₀ to prolong the release pattern of rhINF-α-2b from aquasomes. The rhINF-α-2b-core (CaHPO₄) released 97.3% of protein in 1 h, while 95.3% of rhINF-α-2b was released by rhINF-α-2b-Tre-Aq.somes in 4 h. Concurrently, rhINF-α-2b-Cellob-Aq.somes and rhINF-α-2b-Py-5-P-Aq.somes released 96.2% and 97.8% of rhINF-α-2b respectively in 6 and 8 h. Ultimately, rhINF-α-2b-Py-5-P-Aq.somes-P-PEG₂₀₀₀ displayed evidence of its prolonged release pattern and released 98.1% of rhINF-α-2b in 336 h. FT–IR and XRD substantiated the involvement of vigorous intermolecular hydrogen bonding and amorphous geometry in rhINF-α-2b-Py-5-P-Aq.somes. In last, rhINF-α-2b-Py-5-P-Aq.somes-P-PEG₂₀₀₀ exhibited the ∼ 4.55, 1.92, 2.3, 2.8, and 3.84 fold reductions in IC₅₀ as compared to free rhINF-α-2b, rhINF-α-2b-Py-5-P-Aq.somes, rhINF-α-2b-Cellob-Aq.somes, rhINF-α-2b-Tre-Aq.somes and rhINF-α-2b-Core (CaHPO₄), respectively.ConclusionTherefore, rhINF-α-2b-Py-5-P-Aq.somes-P-PEG₂₀₀₀ warrant further in depth in vitro and in vivo antitumor study to scale up the technology for clinical intervention.     

What Do We Really Know About the Safety of Tai Chi?: A Systematic Review of Adverse Event Reports in Randomized Trials

ObjectiveTo systematically review the frequency and quality of adverse event (AE) reports in randomized controlled trials (RCTs) of tai chi (TC).Data SourcesElectronic searches of PubMed/MEDLINE and additional databases from inception through March 2013 of English-language RCTs. Search terms included tai chi, taiji, and tai chi chuan. Data were independently extracted by 2 investigators.Study SelectionWe included all available RCTs that were published in English and used TC as an intervention. Inclusion and exclusion criteria of studies were reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.Data ExtractionEligible RCTs were categorized with respect to AE reporting: no mention of protocol for monitoring AEs or reports of AEs, and reports of AEs either with or without explicit protocol for monitoring AEs.Data SynthesisThere were 153 eligible RCTs identified; most targeted older adults. Only 50 eligible trials (33%) included reporting of AEs; of these, only 18 trials (12% overall) also reported an explicit AE monitoring protocol. Protocols varied with respect to the rigor of systematic monitoring in both the TC and comparison groups. Reported AEs were typically minor and expected and primarily musculoskeletal related (eg, knee and back pain); no intervention-related serious AEs were reported.ConclusionsTC is unlikely to result in serious AEs, but it may be associated with minor musculoskeletal aches and pains. However, poor and inconsistent reporting of AEs greatly limits the conclusions that can be drawn regarding the safety of TC.     

Effect of Soft Braces on Pain and Physical Function in Patients With Knee Osteoarthritis: Systematic Review With Meta-Analyses

ObjectivesTo systematically review and synthesize the effects of soft braces on pain and on self-reported and performance-based physical function in patients with knee osteoarthritis.Data SourcesThe following electronic databases were searched from inception to April 20, 2016: The Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, EMBASE, CINAHL, SPORTDiscus, Web of Science, and PEDro.Study SelectionRandomized controlled trials (RCTs) and nonrandomized controlled trials (non-RCTs), such as controlled clinical trials, crossover studies, and case-control studies, were included. Two reviewers independently screened articles and determined inclusion through predefined criteria.Data ExtractionData related to participant demographics, study design and methods, interventions, and outcomes, including numerical means and SDs, were extracted by 1 reviewer. Methodological quality assessment was independently performed by 2 reviewers.Data SynthesisEleven studies were identified, including 6 RCTs and 5 non-RCTs. The methodological quality of included RCTs was low. There was a moderate improvement in pain (standardized mean difference [SMD]=.52; 95% confidence interval [CI], .14–.89; P=.007; 284 participants) in favor of wearing a brace compared with not wearing a brace for the immediate, within-group comparison. There was a moderate improvement in pain (SMD=.61; 95% CI, .33–.89; P<.001; 206 participants) and a small to moderate improvement in self-reported physical function (SMD=.39; 95% CI, .11–.67; P=.006; 206 participants) in favor of patients receiving a soft brace versus standard care for the prolonged effect, between-group comparison.ConclusionsCurrently available evidence indicates that soft braces have moderate effects on pain and small to moderate effects on self-reported physical function in knee osteoarthritis. These findings highlight the importance of soft braces as a technique to improve pain and physical function in both the short- and long-term. Additional high-quality studies are warranted to improve confidence in the findings.     

Smoothened activates breast cancer stem-like cell and promotes tumorigenesis and metastasis of breast cancer

Smoothened (Smo) is a G protein-coupled receptor protein encoded by the Smo gene of the hedgehog signalling pathway, which is thought to play an important role in maintaining organ patterning, cell differentiation and self-renewal. The possible role of Smo in the process of tumorigenesis and metastasis of breast cancer still remains unclear. The present experiments were to investigate the effect of Smo on activating breast cancer stem-like CD44⁺CD24⁻ cells and the tumorigenesis and metastasis of breast cancer. By injected CD44⁺CD24⁻ cells (1 × 10⁴) into the cleared fat pad of NOD/SCID mice, it was observed that CD44⁺CD24⁻ cells possess higher tumor-initiating capacity and metastasis properties than equal numbers of non-CD44⁺CD24⁻ cells. The mRNA and protein expressions of Smo in CD44⁺CD24⁻ cells were higher than those in non-CD44⁺CD24⁻ cells, indicating that Smo may play a role in maintaining breast cancer stem cell features. qRT–PCR results revealed that expressions of STAT3, Bcl-2 and cyclinD1 mRNA in MCF-7 cells were decreased after transfected by Smo siRNA. In addition, the expressions of MMP-2 and MMP-9 were downregulated in MCF-7 cells after Smo expression was inhibited. Smo inhibition may be a possible therapeutic target that potentially suppresses breast tumor formation and development.     

Risk Factors for Recurrent Spontaneous Epistaxis

ObjectiveTo identify risk factors associated with spontaneous recurrent epistaxis.Patients and MethodsThis was a retrospective cohort study assessing patients in the Marshfield Clinic system diagnosed as having epistaxis between January 1, 1991, and January 1, 2011. There were 461 cases with at least 2 episodes of spontaneous epistaxis within 3 years and 912 controls with only 1 episode in the same time frame. More than 50 potential risk factors were investigated, including demographic features, substance use, nasal anatomical abnormalities, nasal infectious and inflammatory processes, medical comorbidities, medications, and laboratory values. A Cox proportional hazards regression modeling approach was used to calculate hazard ratios of epistaxis recurrence.ResultsTraditional risk factors for epistaxis, including nasal perforation, nasal septum deviation, rhinitis, sinusitis, and upper respiratory tract infection, did not increase the risk of recurrence. Significant risk factors for recurrent epistaxis included congestive heart failure, diabetes mellitus, hypertension, and a history of anemia. Warfarin use increased the risk of recurrence, independent of international normalized ratio. Aspirin and clopidogrel were not found to increase the risk of recurrence. Few major adverse cardiovascular events were observed within 30 days of the first epistaxis event.ConclusionCongestive heart failure is an underappreciated risk factor for recurrent epistaxis. Hypertension and diabetes mellitus may induce atherosclerotic changes in the nasal vessels, making them friable and more at risk for bleeding. Patients with recurrent epistaxis may also be more susceptible to developing anemia. Physicians should promote antiplatelet and antithrombotic medication adherence despite an increased propensity for recurrent epistaxis to prevent major adverse cardiovascular events.     

Safety and Efficacy of Extracorporeal Shock Wave Myocardial Revascularization Therapy for Refractory Angina Pectoris

ObjectiveTo assess the safety and efficacy of extracorporeal shockwave myocardial revascularization (ESMR) therapy in treating patients with refractory angina pectoris.Patients and MethodsA single-arm multicenter prospective trial to assess safety and efficacy of the ESMR therapy in patients with refractory angina (class III/IV angina) was performed. Screening exercise treadmill tests and pharmacological single-photon emission computed tomography (SPECT) were performed for all patients to assess exercise capacity and ischemic burden. Patients were treated with 9 sessions of ESMR to ischemic areas over 9 weeks. Efficacy end points were exercise capacity by using treadmill test as well as ischemic burden on pharmacological SPECT at 4 months after the last ESMR treatment. Safety measures included electrocardiography, echocardiography, troponin, creatine kinase, and brain natriuretic peptide testing, and pain questionnaires.ResultsFifteen patients with medically refractory angina and no revascularization options were enrolled. There was a statistically significant mean increase of 122.3±156.9 seconds (38% increase compared with baseline; P=.01) in exercise treadmill time from baseline (319.8±157.2 seconds) to last follow-up after the ESMR treatment (422.1±183.3 seconds). There was no improvement in the summed stress perfusion scores after pharmacologically induced stress SPECT at 4 months after the last ESMR treatment in comparison to that at screening; however, SPECT summed stress score revealed that untreated areas had greater progression in ischemic burden vs treated areas (3.69±6.2 vs 0.31±4.5; P=.03). There was no significant change in the mean summed echo score from baseline to posttreatment (0.4±5.1; P=.70). The ESMR therapy was performed safely without any adverse events in electrocardiography, echocardiography, troponins, creatine kinase, or brain natriuretic peptide. Pain during the ESMR treatment was minimal (a score of 0.5±1.2 to 1.1±1.2 out of 10).ConclusionIn this multicenter feasibility study, ESMR seems to be a safe and efficacious treatment for patients with refractory angina pectoris. However, larger sham-controlled trials will be required to confirm these findings.     

Statins and Cognition: A Systematic Review and Meta-analysis of Short- and Long-term Cognitive Effects

ObjectiveTo evaluate the effect of statins on short-term cognitive function and the long-term incidence of dementia.Patients and MethodsA systematic search was performed of MEDLINE, EMBASE, and the Cochrane Central Register from their inception to April 25, 2013. Adults with no history of cognitive dysfunction treated with statins were included from high-quality randomized controlled trials and prospective cohort studies after formal bias assessment.ResultsSixteen studies were included in qualitative synthesis and 11 in quantitative synthesis. Short-term trials did not show a consistent effect of statin therapy on cognitive end points. Digit Symbol Substitution Testing (a well-validated measure of cognitive function) was the most common short-term end point, with no significant differences in the mean change from baseline to follow-up between the statin and placebo groups (mean change, 1.65; 95% CI, –0.03 to 3.32; 296 total exposures in 3 trials). Long-term cognition studies included 23,443 patients with a mean exposure duration of 3 to 24.9 years. Three studies found no association between statin use and incident dementia, and 5 found a favorable effect. Pooled results revealed a 29% reduction in incident dementia in statin-treated patients (hazard ratio, 0.71; 95% CI, 0.61-0.82).ConclusionIn patients without baseline cognitive dysfunction, short-term data are most compatible with no adverse effect of statins on cognition, and long-term data may support a beneficial role for statins in the prevention of dementia.     

Relationship of Body Mass Index With Total Mortality,Cardiovascular Mortality,and Myocardial Infarction After Coronary Revascularization: Evidence From a Meta-analysis

ObjectiveTo investigate the relationship of body mass index (BMI) with total mortality, cardiovascular (CV) mortality, and myocardial infarction (MI) after coronary revascularization procedures (coronary artery bypass grafting [CABG] and percutaneous coronary intervention [PCI]).Patients and MethodsSystematic search of studies was conducted using PubMed, CINAHL, Cochran CENTRAL, Scopus, and the Web of Science databases. We identified studies reporting the rate of MI, CV mortality, and total mortality among coronary artery disease patients' postcoronary revascularization procedures in various BMI categories: less than 20 (underweight), 20-24.9 (normal reference), 25-29.9 (overweight), 30-34.9 (obese), and 35 or more (severely obese). Event rates were compared using a random effects model assuming interstudy heterogeneity.ResultsA total of 36 studies (12 CABG; 26 PCI) were selected for final analyses. The risk of total mortality (relative risk [RR], 2.59; 95% CI, 2.09-3.21), CV mortality (RR, 2.67; 95% CI, 1.63-4.39), and MI (RR, 1.79; 95% CI, 1.28-2.50) was highest among patients with low BMI at the end of a mean follow-up period of 1.7 years. The risk of CV mortality was lowest among overweight patients (RR, 0.81; 95% CI, 0.68-0.95). Increasing degree of adiposity as assessed by BMI had a neutral effect on the risk of MI for overweight (RR, 0.92; 95% CI, 0.84-1.01), obese (RR, 0.99; 95% CI, 0.85-1.15), and severely obese (RR, 0.93; 95% CI, 0.78-1.11) patients.ConclusionAfter coronary artery disease revascularization procedures (PCI and CABG), the risk of total mortality, CV mortality, and MI was highest among underweight patients as defined by low BMI and CV mortality was lowest among overweight patients.     

Psychiatric Adverse Effects of Pediatric Corticosteroid Use

Corticosteroids, highly effective drugs for myriad disease states, have considerable neuropsychiatric adverse effects that can manifest in cognitive disorders, behavioral changes, and frank psychiatric disease. Recent reviews have summarized these effects in adults, but a comprehensive review on corticosteroid effects in children has not been published since 2005. Here, we systematically review articles published since then that, we find, naturally divide into 3 main areas: (1) chronic effects of acute prenatal and neonatal exposure associated with prematurity and congenital conditions; (2) immediate behavioral effects of acute exposure via oncological protocols; and (3) acute behavioral effects of sporadic use in children and adolescents with other conditions. PsycInfo, MEDLINE, Embase, and Scopus were queried to identify articles reporting psychiatric adverse effects of corticosteroids in pediatric patients. Search terms included corticosteroids, adrenal cortex hormones, steroid psychosis, substance-induced psychoses, glucocorticoids, dexamethasone, hydrocortisone, prednisone, adverse effects, mood disorders, mental disorders, psychosis, psychotic, psychoses, side effect, chemically induced, emotions, affective symptoms, toxicity, behavior, behavioral symptoms, infant, child, adolescent, pediatric, paediatric, neonatal, children, teen, and teenager. Following guidelines for systematic reviews from the Potsdam Consultation on Meta-Analysis, we have found it difficult to draw specific conclusions that are more than general impressions owing to the quality of the available studies. We find a mixed picture with neonates exposed to dexamethasone, with some articles reporting eventual deficits in neuropsychiatric functioning and others reporting no effect. In pediatric patients with acute lymphoblastic leukemia, corticosteroid use appears to correlate with negative psychiatric and behavioral effects. In children treated with corticosteroids for noncancer conditions, adverse effects have been observed both during treatment and after cessation, although the data from article to article are not consistent enough to establish dose relationships. By and large, inhaled corticosteroids are considered safe and free of severe neuropsychiatric effects. Although both antipsychotic medications and benzodiazepines have been used to treat corticosteroid-induced mania and psychosis, no unified management strategy has emerged. Large-scale standardized investigations are needed to clarify the psychiatric effect of corticosteroids on children in all these conditions. Meanwhile, there is general agreement that patients as well as caregivers should be warned of the potential for behavioral adverse effects when patients receive these drugs.     

Supervised Exercise–Based Intervention to Prevent Excessive Gestational Weight Gain: A Randomized Controlled Trial

ObjectiveTo study the effect on maternal weight gain of a supervised light- to moderate-intensity exercise–based intervention performed from the ninth week of pregnancy.Participants and MethodsA total of 962 healthy pregnant women were randomly assigned to a standard care or exercise intervention group conducted between September 1, 2007, and January 31, 2011. The intervention included light- to moderate-intensity aerobic and resistance exercises performed 3 days a week (50-55 minutes per session). Excessive gestational weight gain was calculated on the basis of the 2009 Institute of Medicine (IOM) recommendations. Gestational body weight gain was calculated on the basis of the weight measured at the first prenatal visit (fifth to sixth weeks of gestation) and weight measured at the last visit to the clinic before delivery. Women were categorized into normal weight or overweight or obese.ResultsWomen in the intervention group gained less weight (adjusted mean difference, 1.039 kg; 95% CI, 0.534-1.545 kg; P<.001) and were less likely to gain weight above the IOM recommendations (odds ratio, 0.625; 95% CI, 0.461-0.847) compared with those in the standard care group. The main treatment effects according to body mass index category were that normal weight women in the intervention group gained less weight (adjusted mean difference, 1.393 kg; 95% CI, 0.813-1.972 kg; P<.001) and were less likely to gain weight above the IOM recommendations (odds ratio, 0.508; 95% CI, 0.334-0.774) than normal weight women who received standard care. No significant treatment effect was observed in overweight or obese women.ConclusionSupervised exercise of light to moderate intensity can be used to prevent excessive gestational weight gain, especially in normal weight women.Trial registrationclinicaltrials.gov Identifier: NCT01790347