Effective Adjunctive Therapy Research Articles

Differing Causes of Lactic Acidosis and Deep Breathing in Cerebral Malaria and Severe Malarial Anemia May Explain Differences in Acidosis-Related Mortality.

Lactic acidosis (LA) is a marker for mortality in severe malaria, but the mechanisms that lead to LA in the different types of severe malaria and the extent to which LA-associated mortality differs by type of severe malaria are not well described. We assessed the frequency of LA in children admitted to Mulago Hospital, Kampala, Uganda with cerebral malaria (CM, n = 193) or severe malarial anemia (SMA, n = 216). LA was compared to mortality and measures of parasite biomass and sequestration (P. falciparum histidine-rich protein-2 (PfHRP2) concentration, platelet count), and to a measure of systemic tissue oxygen delivery (hemoglobin level). LA was more frequent in children with SMA than CM (SMA, 47.7%, CM, 34.2%, P = 0.006), but mortality was higher in children with CM (13.0%) than SMA (0.5%, P<0.0001). In CM, LA was associated with increased PfHRP2 concentration and decreased platelet count but was not associated with hemoglobin level. In contrast, in SMA, LA was associated with a decreased hemoglobin level, but was not associated with PfHRP2 concentration or platelet count. LA was related to mortality only in CM. In multivariable regression analysis of the effect PfHRP2 and hemoglobin levels on LA and DB, only PfHRP2 level increased risk of LA and DB in CM, while in SMA, elevated hemoglobin strongly decreased risk of LA and DB, and PfHRP2 level modestly increased risk of LA. The study findings suggest that LA in CM is due primarily to parasite sequestration, which currently has no effective adjunctive therapy, while LA in SMA is due primarily to anemia, which is rapidly corrected with blood transfusion. Differing etiologies of LA in CM and SMA may explain why LA is associated with mortality in CM but not SMA.

Erratum to: Cost-effectiveness of clostridial collagenase ointment on wound closure in patients with diabetic foot ulcers: economic analysis of results from a multicenter, randomized, open-label trial

[This corrects the article DOI: 10.1186/s13047-015-0065-x.].

PCSK9 Inhibitors

Objective: To evaluate the safety and efficacy of 2 human monoclonal antibodies, alirocumab and evolocumab, on reduction of low-density lipoprotein cholesterol (LDL-C), cardiovascular benefits, and their place in current practice. Data Sources: A search of MEDLINE and Scopus databases (1966 to May 2016) with search terms “alirocumab,” “evolocumab,” “LDL,” and “PCSK9.” Study Selection and Data Extraction: The search identified phase 3 randomized control trials in English language in the past 10 years that studied LDL-C reduction of alirocumab or evolocumab. The studies were assessed for all efficacy and safety endpoints. Data Synthesis: Twelve total studies were identified evaluating alirocumab or evolocumab. These monoclonal antibodies have been shown to significantly decrease LDL-C as monotherapy and in combination with statins in phase 3 clinical trials in patients with primary hypercholesterolemia as well as familial hypercholesterolemia by inhibiting PCSK9. Alirocumab significantly reduced LDL-C by up to 61%, while evolocumab significantly reduced LDL-C by up to 66%. Adverse effects of these medications have been low and overall well tolerated. Conclusion: Although these monoclonal antibodies have shown to significantly reduce LDL-C, their effect on cardiovascular outcomes has not yet been determined. Further studies are being conducted to assess the cardiovascular benefit of both alirocumab and evolocumab. Until these studies demonstrate a reduction in atherosclerotic cardiovascular disease risk, statins should remain first-line therapy for most patients. However, alirocumab and evolocumab can be used as an effective adjunctive therapy option to lower LDL-C or in patients who are statin intolerant.

Cardiac Resynchronization Therapy MayBe Antiarrhythmic Particularly inResponders: A Systematic Review and Meta-Analysis.

This study sought to study the effect of echocardiographic response to cardiac resynchronization therapy (CRT) on ventricular arrhythmias (VA). The effect of CRT-defibrillator on sustained VA was compared with implantable cardioverter-defibrillator (ICD)-only therapy. CRT is an effective adjunctive therapy in selected patients with advanced congestive heart failure, but its effect on VA remains controversial. PubMed was searched to identify studies. For primary comparison, studies reporting incidence of VA in patients with congestive heart failure with CRT compared with ICD were included. For secondary comparison, studies reporting incidence of VA in echocardiographic responders compared with nonresponders were included. Studies reporting incidence of VA in CRT nonresponders before and after CRT upgrade from ICD were assessed for the third comparison. Inverse variance method in a random-effects model was used to combine effect sizes. Thirteen studies (4,631 subjects) were included in the primary meta-analysis. Patients with CRT had a significantly lower incidence of VA compared with patients with ICD only (odds ratio: 0.754; confidence interval: 0.594 to 0.959). Thirteen studies (n= 3,667) were included in the meta-analysis of VA in CRT responders versus nonresponders. Responders had a significantly lower risk of VA (odds ratio: 0.436; confidence interval: 0.323 to 0.589). Multivariate meta-regression showed that the percentage beta-blocker use and follow-up duration explained heterogeneity between the studies. Three studies were included in the comparison of VA in CRT nonresponders before and after upgrade from ICD. CRT nonresponders had an elevated risk of VA compared with ICD-only subjects (odds ratio: 1.497; confidence interval: 1.225 to 1.829). CRT may significantly reduce risk of VA compared with ICDs in patients who meet criteria for CRT. CRT responders have significant reduction in VA compared with nonresponders. CRT nonresponse might significantly increase risk of VA.

Systematic Review of Traumatic Brain Injury and the Impact of Antioxidant Therapy on Clinical Outcomes

Traumatic brain injury (TBI) is an acquired brain injury that occurs when there is sudden trauma that leads to brain damage. This acute complex event can happen when the head is violently or suddenly struck or an object pierces the skull or brain. The current principal treatment of TBI includes various pharmaceutical agents, hyperbaric oxygen, and hypothermia. There is evidence that secondary injury from a TBI is specifically related to oxidative stress. However, the clinical management of TBI often does not include antioxidants to reduce oxidative stress and prevent secondary injury. The purpose of this article is to examine current literature regarding the use of antioxidant therapies in treating TBI. This review evaluates the evidence of antioxidant therapy as an adjunctive treatment used to reduce the underlying mechanisms involved in secondary TBI injury. A systematic review of the literature published between January 2005 and September 2015 was conducted. Five databases were searched including CINAHL, PubMed, the Cochrane Library, PsycINFO, and Web of Science. Critical evaluation of the six studies that met inclusion criteria suggests that antioxidant therapies such as amino acids, vitamins C and E, progesterone, N-acetylcysteine, and enzogenol may be safe and effective adjunctive therapies in adult patients with TBI. Although certain limitations were found, the overall trend of using antioxidant therapies to improve the clinical outcomes of TBI was positive. By incorporating antioxidant therapies into practice, clinicians can help attenuate the oxidative posttraumatic brain damage and optimize patients' recovery.

Is rhythmic sensory stimulation an effective adjunctive therapy for fibromyalgia? Preliminary results

Is rhythmic sensory stimulation an effective adjunctive therapy for fibromyalgia? Preliminary results

Optimizing the use of intravenous magnesium sulfate for acute asthma treatment in children.

Asthma is the most common pediatric chronic disease and currently affects 7.1 million children in the United States. Many children experience acute asthma exacerbations. Many children also require hospitalization despite treatment in an emergency department with current standard therapy (corticosteroids, albuterol, and ipratropium). These hospitalizations may be avoided if effective adjunctive therapies can be developed to adequately treat severe exacerbations. Publications were searched in the PubMed database using the following keywords: magnesium AND asthma AND children AND randomized controlled trial. A total of 30 publications were returned. References of relevant articles were also screened. We included publications of controlled randomized trials where intravenous magnesium sulfate was studied in children (age < 18 years) with acute asthma (n = 7). We excluded studies in adults or trials with other formulations of magnesium (e.g., nebulized). Previous studies have demonstrated that intravenous magnesium sulfate (IV MgSO4 ) significantly improves respiratory function and reduces hospitalization rate in children with moderate to severe asthma exacerbations. Current dosing regimens involve a short infusion of 25-75 mg/kg over 20 min (maximum 2-2.5 g/dose), though no studies have directly compared dosages for relative efficacy. Several studies suggest utilizing a peak plasma concentration of magnesium higher than 4 mg/dL as a surrogate of efficacy. This review summarizes the literature regarding the use of IV MgSO4 for the treatment of pediatric acute asthma. We suggest that optimized dosing regimens could be developed using a linked pharmacokinetic-pharmacodynamic modeling and simulation approach. We propose the factors that should be considered in future clinical trial design in order to better understand the use of IV MgSO4 in pediatric acute asthma. Pediatr Pulmonol. 2016;51:1414-1421. © 2016 Wiley Periodicals, Inc.

Combining an epithelial repair factor and anti-fibrotic with a corticosteroid offers optimal treatment for allergic airways disease.

We evaluated the extent to which individual versus combination treatments that specifically target airway epithelial damage [trefoil factor-2 (TFF2)], airway fibrosis [serelaxin (RLX)] or airway inflammation [dexamethasone (DEX)] reversed the pathogenesis of chronic allergic airways disease (AAD). Following induction of ovalbumin (OVA)-induced chronic AAD in 6–8 week female Balb/c mice, animals were i.p. administered naphthalene (NA) on day 64 to induce epithelial damage, then received daily intranasal administration of RLX (0.8 mg·mL(−1)), TFF2 (0.5 mg·mL(−1)), DEX (0.5 mg·mL(−1)), RLX + TFF2 or RLX + TFF2 + DEX from days 67–74. On day 75, lung function was assessed by invasive plethysmography, before lung tissue was isolated for analyses of various measures. The control group was treated with saline + corn oil (vehicle for NA). OVA + NA-injured mice demonstrated significantly increased airway inflammation, airway remodelling (AWR) (epithelial damage/thickness; subepithelial myofibroblast differentiation, extracellular matrix accumulation and fibronectin deposition; total lung collagen concentration), and significantly reduced airway dynamic compliance (cDyn). RLX + TFF2 markedly reversed several measures of OVA + NA-induced AWR and normalized the reduction in cDyn. The combined effects of RLX + TFF2 + DEX significantly reversed peribronchial inflammation score, airway epithelial damage, subepithelial extracellular matrix accumulation/fibronectin deposition and total lung collagen concentration (by 50–90%) and also normalized the reduction of cDyn. Combining an epithelial repair factor and anti-fibrotic provides an effective means of treating the AWR and dysfunction associated with AAD/asthma and may act as an effective adjunct therapy to anti-inflammatory corticosteroids

Protein-bound uremic toxins: a long overlooked culprit in cardiorenal syndrome.

Protein-bound uremic toxins (PBUTs) accumulate once renal excretory function declines and are not cleared by dialysis. There is increasing evidence that PBUTs exert toxic effects on many vital organs, including the kidney, blood vessels, and heart. It has been suggested that PBUTs are likely to be a potential missing link in cardiorenal syndrome, based on the high incidence of cardiovascular events and mortality in the dialysis population, which are dramatically reduced in successful kidney transplant recipients. These data have led the call for more effective dialysis or additional adjunctive therapy to eradicate these toxins and their adverse biological effects. Indoxyl sulfate and p-cresyl sulfate are the two most problematic PBUTs, conferring renal and cardiovascular toxicity, and are derived from dietary amino acid metabolites by colonic microbial organisms. Therefore, targeting the colon where these toxins are initially produced appears to be a potential therapeutic alternative for patients with chronic kidney disease. This strategy, if approved, is likely to be applicable to predialysis patients, thereby potentially preventing progression of chronic kidney disease to end-stage renal disease as well as preventing the development of cardiorenal syndrome.

Laser Therapy in the Management of Diabetic Retinopathy

Diabetic macular edema is the major cause of decreased vision in diabetic patients. This review explores laser treatment options beyond the established focal/grid laser photocoagulation protocol initially demonstrated in the Early Treatment of Diabetic Retinopathy Study. Subthreshold micropulse laser has been shown to be effective adjunctive therapy in conjunction with intravitreal anti-angiogenic injections in a subset of patients, specifically in those with a retinal thickness of less than 400 μm, without the risk of scotomas and potential vision loss, which can occur with conventional laser. Given the absence of scarring from this “invisible” laser, subthreshold micropulse laser may allow for earlier treatment prior to the onset of clinically significant macular edema, potentially preventing symptomatic vision loss and permanent photoreceptor damage.

Intra‐renal and Urinary Oxygenation during Resuscitation with Norepinephrine and Angiotensin II in Ovine Acute Kidney Injury

Background and AimsAcute kidney Injury (AKI) is a common phenotype of sepsis leading to high mortality rates. Norepinephrine (NE) is the first choice vasopressor used clinically to restore blood pressure and renal function, whilst there is emerging interest in angiotensin II (Ang II) as an effective adjunctive therapy in patients with septic shock. Increasing evidence suggests that hypoxia in the renal medulla may play a critical role in the pathogenesis of AKI. We therefore measured renal cortical and medullary tissue oxygen tension (PO2) in conscious sheep during development of septic AKI and following resuscitation with NE and Ang II. In addition, since the renal medullary vasa recta run close and parallel to the collecting ducts, we examined whether urinary PO2 and medullary tissue PO2 changed in a similar manner during development of septic AKI and treatment with NE and Ang II.MethodsSheep were surgically instrumented with a renal artery flow probe and fibre‐optic probes in the cortex and medulla to measure tissue perfusion and oxygenation. An oxygen probe was inserted into the tip of the bladder catheter for measurement of urinary oxygenation. Conscious sheep received a continuous infusion of live Escherichia coli (2.8 × 109 bolus + 1.26 × 109 colony forming units i.v) for 32 h. NE (0.4–0.8 μg/kg/h, n=8) or Ang II (0.5–33μg/kg/min, n=8) or saline‐vehicle (n=8) were infused from 24–30 h of sepsis.ResultsPrior to treatment, septic AKI was characterized by hypotension (~14 mmHg), renal hyperperfusion (~70%) and reduced glomerular filtration rate (~65%). Medullary perfusion (1289±95 to 628±113 blood perfusion units (BPU)), medullary oxygenation (32±3 to 16±4 mmHg) and urinary oxygenation (36±2 to 24±2 mmHg) were all significantly reduced. Restoring blood pressure with NE further reduced medullary perfusion (331±64 BPU), medullary PO2 (8±2 mmHg) and urinary PO2 (18±4 mmHg). In contrast, Ang II reversed the sepsis‐induced hypotension without further exacerbating medullary perfusion (553±58 BPU), medullary PO2 (26±2 mmHg) or urinary PO2 (24±1 mmHg). Cortical perfusion and oxygenation were preserved during development of septic AKI and resuscitation with NE and Ang II.ConclusionsRenal medullary hypoxia due to intra‐renal blood flow redistribution may contribute to the development of septic AKI. Resuscitation with NE reversed sepsis‐induced hypotension, but exacerbated the medullary hypoxia, which may have long‐term effects to worsen kidney injury. Interestingly, Ang II restored blood pressure without worsening medullary hypoxia, suggesting that Ang II has less adverse effects than NE on kidney oxygenation during treatment of septic AKI. The parallel changes in medullary tissue and urinary PO2 during development of sepsis and vasopressor treatment suggest that urinary PO2 may be a useful real‐time biomarker to monitor patients at risk of developing AKI.Support or Funding InformatioThis work was supported by grants from the National Health and Medical Research Council of Australia (NHMRC, 454615, 1009280, 1050672), and by funding from the Victorian Government Operational Infrastructure Support Grant.

Renal cell carcinoma with thrombus extending to the hepatic veins or right atrium: operative strategies based on 41 consecutive patients.

The natural history of renal cell carcinoma (RCC) with tumour thrombus extending at or above the hepatic veins is dismal. Different surgical approaches have been described including cardiopulmonary bypass (CPB) with deep hypothermic circulatory arrest. We here report our experience in terms of surgical techniques and outcomes on 41 consecutive patients presenting an RCC extending to the hepatic veins or the right atrium. A surgical decision-making algorithm is discussed. Retrospective review of 41 patients operated for RCC extending in the retrohepatic vena cava (extent level III-IV) between 2000 and 2015. Patients were operated by a dedicated urology/cardiac surgery team. The mean age was 62.6 ± 10.4 years; 39% were female. Surgery was emergent in 7.3% of patients, 2.4% of patients had preoperative dialysis, 4.9% required a redo sternotomy and 19.5% had coronary artery disease. Tumour thrombus extended above the diaphragm in 23 patients (level IV) and to the level of hepatic veins (level III) in 18 patients. CPB was used in 38 patients. Arterial cannulation was in the aorta or femoral artery in 14 patients during the initial experience. In the current era, the axillary artery and the innominate artery were used in 12 patients each. Mean CPB, cross-clamp and circulatory arrest times were, respectively, 96.5 ± 42.9, 21.1 ± 16.4 and 10.2 ± 8.2 min (mean temperature of 25.7 ± 4.9°C). Hepatic exclusion without the use of CPB was performed to excise the thrombus in 3 patients. A right nephrectomy was performed in 25 patients, a left in 15 patients and a bilateral nephrectomy in 1 patient. Five patients had a partial inferior vena cava (IVC) resection, with 4 patients requiring a patch reconstruction of the IVC. Three patients had an infrarenal IVC ligation. One patient suffered a cerebrovascular accident in the postoperative period. One in-hospital death occurred (in-hospital mortality 2.4%). The mean follow-up was 1.9 ± 2.0 years. Twenty-three patients died during follow-up; 21 were disease-related. Three-year survival rate was 37.1%. High-level RCC tumour thrombus is a rare clinical entity, the treatment of which is complex and requires dedicated operative teams. The operative technique should be tailored according to the level of extension and the extent of vena cava obstruction/occlusion of the tumour thrombus. Contemporary operative techniques may be conducted with excellent results. Mid-term survival is limited, supporting the necessity to pursue research efforts towards establishing effective adjunct therapies.

The Characterization of an Adrenergic Signalling System Involved in the Encystment of the Ocular Pathogen Acanthamoeba spp.

The aim of this study was to identify and characterize the receptor system involved in controlling encystment in Acanthamoeba using specific agonists and antagonists and to examine whether endogenous stores of catecholamines are produced by the organism. Acanthamoeba trophozoites suspended in axenic growth medium were exposed to adrenoceptor agonists and antagonists to determine which compounds promoted or prevented encystment. Second, trophozoites were cultured in medium containing a catecholamine synthesis inhibitor to investigate the effect this had on natural encystment. Nonspecific adrenoceptor agonists including epinephrine, isoprotenerol, and the selective β1 adrenoceptor agonist dobutamine were found to cause >90% encystment of Acanthamoeba trophozoites compared to <30% with the controls. The selective β1 antagonist metoprolol was able to inhibit epinephrine mediated encystment by >55%. Cultures of Acanthamoeba with the catecholamine synthesis inhibitor α-methyl-p-tyrosine significantly reduced the level of amoebic encystment compared to controls. In conclusion, Acanthamoeba appear to contain a functional adrenergic receptor system of unknown structure which is involved in initiating the encystment process that can be activated and blocked by β1 agonists and antagonists respectively. Furthermore, the presence of this receptor system in Acanthamoeba indicates that topical β adrenoceptor blockers may be effective adjunct therapy by reducing the transformation of trophozoites into the highly resistant cyst stage.

A training programme involving automatic self-transcending meditation in late-life depression: preliminary analysis of an ongoing randomised controlled trial.

Late-life depression affects 2–6% of seniors aged 60 years and above. Patients are increasingly embracing non-pharmacological therapies, many of which have not been scientifically evaluated. This study aimed to evaluate a category of meditation, automatic self-transcending meditation (ASTM), in alleviating symptoms of depression when augmenting treatment as usual (NCT02149810). The preliminary results of an ongoing single-blind randomised controlled trial comparing a training programme involving ASTM with a wait-list control indicate that a 12-week ASTM programme may lead to significantly greater reductions in depression and anxiety severity. As such, ASTM may be an effective adjunctive therapy in the treatment of late-life depression.Declaration of interestR.I.N. is Director of Research and Health Promotion for the Art of Living Foundation, Canada and supervised the staff providing ASTM training.Copyright and usage© The Royal College of Psychiatrists 2016. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence.

Therapeutic effects of connective tissue manipulation on wound healing and bacterial colonization count among patients with diabetic foot ulcer

This study investigated the therapeutic effects of connective tissue manipulation (CTM) in diabetic foot ulcer (DFU). A total of 20 participants (10 in CTM group and 10 in conventional treatment group (CG)) with DFU underwent the conventional DFU treatment. In addition, the CTM group received CTM twice per week for 6 weeks. The percentage wound area reduction (PWAR) and bacterial colonization count (BCC) in log10colony-forming units (CFU) per ml wound fluid was evaluated at baseline and six weeks. Results showed a significant change in PWAR in CTM (p<0.05, t=3.82, Df=9, CI L=0.98 U=3.81) and CG (p<0.05, t=2.97, Df=9,CI L=0.26 U=1.98). Mean reduction of BCC showed a significant reduction (p<0.05), with percentage of BCC reduction higher in CTM group (6.45%) than CG (3.55%). The findings suggest CTM as an effective adjunct therapy for DFU to enhance conventional treatments.

Ascorbic acid supplementation improves skeletal muscle oxidative stress and insulin sensitivity in people with type 2 diabetes: Findings of a randomized controlled study

Aim/hypothesisSkeletal muscle insulin resistance and oxidative stress are characteristic metabolic disturbances in people with type 2 diabetes. Studies in insulin resistant rodents show an improvement in skeletal muscle insulin sensitivity and oxidative stress following antioxidant supplementation. We therefore investigated the potential ameliorative effects of antioxidant ascorbic acid (AA) supplementation on skeletal muscle insulin sensitivity and oxidative stress in people with type 2 diabetes. MethodsParticipants with stable glucose control commenced a randomized cross-over study involving four months of AA (2×500mg/day) or placebo supplementation. Insulin sensitivity was assessed using a hyperinsulinaemic, euglycaemic clamp coupled with infusion of 6,6-D2 glucose. Muscle biopsies were measured for AA concentration and oxidative stress markers that included basal measures (2′,7′-dichlorofluorescin [DCFH] oxidation, ratio of reduced-to-oxidized glutathione [GSH/GSSG] and F2-Isoprostanes) and insulin-stimulated measures (DCFH oxidation). Antioxidant concentrations, citrate synthase activity and protein abundances of sodium-dependent vitamin C transporter 2 (SVCT2), total Akt and phosphorylated Akt (ser473) were also measured in muscle samples. ResultsAA supplementation significantly increased insulin-mediated glucose disposal (delta rate of glucose disappearance; ∆Rd) (p=0.009), peripheral insulin-sensitivity index (p=0.046), skeletal muscle AA concentration (p=0.017) and muscle SVCT2 protein expression (p=0.008); but significantly decreased skeletal muscle DCFH oxidation during hyperinsulinaemia (p=0.007) when compared with placebo. Total superoxide dismutase activity was also lower following AA supplementation when compared with placebo (p=0.006). Basal oxidative stress markers, citrate synthase activity, endogenous glucose production, HbA1C and muscle Akt expression were not significantly altered by AA supplementation. Conclusions/interpretationIn summary, oral AA supplementation ameliorates skeletal muscle oxidative stress during hyperinsulinaemia and improves insulin-mediated glucose disposal in people with type 2 diabetes. Findings implicate AA supplementation as a potentially inexpensive, convenient, and effective adjunct therapy in the treatment of insulin resistance in people with type 2 diabetes.

Effect of kinesio taping on the isokinetic muscle function in football athletes with a knee injury.

[Purpose] The purpose of this study was to determine the difference in isokinetic muscle function in football athletes with a knee injury with and without kinesio taping. [Subjects] The subjects for this study were 10 football athletes (males) with a knee injury. [Methods] Measurements were performed by using Cybex dynamometer under uniform motion before and after the application of kinesio tape to the quadriceps and hamstring muscle. Maximal concentric knee extension and flexion at three angular velocities (60°/s, 120°/s, and 180°/s) were measured. [Results] A significant difference was found in peak torque and total work of the flexion at 120°/s and 180°/s, as well as in the average power of extension at 180°/s. [Conclusion] Though it is not the main therapy for muscle function in football athletes with injury, kinesio taping was an effective adjunct therapy.

The Application of Rotational Atherectomy in PCI of Coronary Chronic Total Occlusions

Objective:The aim of the study is to investigate the effi cacy, complication rate and predictors of rotational atherectomy (RA) usage after successful guidewire crossing during percutaneous coronary intervention (PCI) of coronary chronic total occlusion (CTO).Methods:A single center experience of 525 consecutive patients from October 2010 to June 2014. A total of 587 CTO lesions were treated. After successful guidewire crossing, lesions that could not be crossed with the smallest 1.25mm balloon underwent RA with 1.25mm and or 1.5mm burrs after exchanging for the Rotawire through a microcatheter. Post RA, the CTO lesions are then pre-dilated successfully before stenting with drug eluting stents (DES). Patients were then clinically followed up for inpatient MACE and restenosis.Results:587 CTO lesions in 525 patients were treated. The mean age of patients was 61.6 ± 10.2 years-old. 30% had diabetes mellitus. Mean LVEF was 56 ± 12%. The overall successful CTO PCI rate was 87%. 22% required the retrograde CTO approach. 26 CTO lesions in 26 patients (4.43%) underwent RA. RA and stent deployment were successfully performed in 25 patients. One lesion was unsuccessful because the Rotawire could not cross the lesion. Reference lesion diameter was 2.87±0.55mm,18 cases used the 1.25mm burr and 7 cases used the 1.5mm burr. Reference burr / vessel diameter ratio was 0.46± 0.20mm. No patients required adjunct 2b3a inhibitor usage. The procedural success rate was 96.2% and no peri-procedural MACE was observed.Conclusion:RA was a safe and effective adjunct therapy for calcifi ed CTO lesions that failed balloon dilatation.

Long-Term Outcome of Vagus Nerve Stimulation Therapy in Young Children with Intractable Epilepsy

Vagus nerve stimulation (VNS) is approved by FDA for treatment of intractable epilepsy in children over 12 years of age. We assessed the efficacy of VNS therapy in younger children. The study was a retrospective review of the medical records of medically refractory epilepsy patients under 12 years old at VNS implantation. Out of 42 patients studied, 28 had at least 50% decrease in seizure frequency, one-half of patients had 75% decrease in seizures, and 7% became seizure-free. A total 69% of patients reported improved mood and alertness. Complication rate was 7%. Age at VNS implantation, prior duration of epilepsy, electroencelphographic focality, and etiology of epilepsy did not influence the outcome ( p > 0.05). Our cohort demonstrated a lasting benefit of VNS therapy over 5 years, including seizure reduction and improved mood and alertness. VNS is a safe and effective adjunctive therapy for young children with medically intractable epilepsy.

Efficacy and safety of lacosamide as an adjunctive therapy for refractory focal epilepsy in paediatric patients: a retrospective single-centre study.

Lacosamide is an antiepileptic drug approved for the treatment of focal epilepsy in adult patients. The aim of this observational study was to review our centre's experience with lacosamide and to characterize its effectiveness and tolerability as an adjunctive antiepileptic drug in a retrospective cohort of children with refractory focal epilepsy. We retrospectively reviewed the medical records of 22 patients who received lacosamide from November 2009 to April 2014 at the CHU Ste-Justine, University of Montreal. Treatment responders were defined as children with a ≥50% reduction in seizure frequency compared to baseline, and this was determined three months after the initiation of treatment and at the last follow-up visit. We included 14 boys and eight girls with a mean age of 12.9 years (SD: 5.2; range: 5.2-20.7 years) at the initiation of treatment. The average length of follow-up was 11.9 months. Patients had previously received an average of 7.5 antiepileptic drugs. The mean number of concomitant antiepileptic drugs was 2.3. The mean initial and maintenance doses were 2.9 and 8.4 mg/kg/d, respectively. Thirteen (59%) and ten (45%) patients were responders after three months of treatment and at the last follow-up visit, respectively. One became seizure-free. Adverse effects were reported in 11 patients and none were severe. Responders and non-responders were identical with respect to all studied parameters except gender, with the proportion of responders being greater in girls than in boys (75% vs 29%; p=0.035). Our study adds evidence that lacosamide appears to be a safe and effective adjunctive therapy for children with refractory focal epilepsy.