Faster Onset Of Action Research Articles

Characterisation of a novel, multifunctional, co-processed excipient and its effect on release profile of paracetamol from tablets prepared by direct compression

ObjectiveTo characterise a novel multifunctional pharmaceutical excipient and investigate its effect on paracetamol release from tablets prepared by direct compression. MethodsThe excipient was prepared by co-processing gelatinized maize starch with sodium carboxymethyl cellulose and microcrystalline cellulose in a ratio of 2:1:1, dried and pulverized into powder. The excipient formulated was characterized using Fourier transform infrared spectroscopy and differential scanning calorimetry. The excipient was used to prepare batches of tablets by direct compression with drug-excipient ratios of 1:1, 1:2, 1:3 and 1:4. Parameters evaluated on tablets include crushing strength, friability and in vitro dissolution studies. ResultsDifferential scanning calorimetry analysis revealed a crystalline excipient while Fourier transform infrared spectroscopy showed no interaction between the excipient and paracetamol. Tablets from all the batches gave average crushing strength values between 3.47 and 4.88 kp. The 1:1 and 1:2 tablet batches were comparable to each other while 1:3 and 1:4 were also comparable to one another in their dissolution profiles. The dissolution parameters of the 1:4 batch was faster with – m∞ (90.5%), t50% (3.5 min), t70% (11.6 min) while that of ratio 1:1 was the least with – m∞ (48.6%), m5min (23.8%). Their release kinetics followed a Korsmeyer–Peppas model with a super case-II transport mechanism. ConclusionsThe drug-excipient ratios of 1:3 and 1:4 gave pharmaceutically acceptable tablets that met the British Pharmacopoeia specifications. The t50% value of the 1:4 batch of tablets may find its usefulness in formulating drugs for which a fast onset of action is desired.

A prospective case series evaluating efficacy and safety of combination of itraconazole and potassium iodide in rhinofacial conidiobolomycosis.

Rhinofacial conidiobolomycosis (RFC) is an uncommon subcutaneous fungal infection producing painless swelling with grotesque deformity of the face. Although there are case reports and small case series; there are very few prospective studies evaluating treatment outcome and long-term follow-up. To evaluate the safety and efficacy of combination of itraconazole (200mg twice daily) and saturated solution of potassium iodide (SSKI) in patients with RFC. Ten patients of RFC were studied over a period of 5years. Diagnosis was confirmed by clinical, histopathological, and microbiological evaluation. Conidiobolus was cultured in four cases and in the rest of the cases, the histopathology was suggestive of RFC. They were treated with itraconazole (200mg twice daily) and SSKI and followed up for a minimum of 1year after stopping treatment. The mean age was 38.7years and the mean duration of symptoms was 22.4months. Males were predominantly involved (9:1). Seven patients responded to thecombination treatment, five had complete resolution and two had good improvement (50-75%); however, in two patients the response was minimal (<25% regression of the swelling) and one patient did not show any improvement after 6months of treatment. Combination of itraconazole and SSKI is an effective treatment modality for RFC with relatively faster onset of action, low relapse rates, and minimal adverse effects. It can be considered as first-line treatment in patients with RFC.

Non-Antidepressant Pharmacologic Long-Term Treatment of Panic Disorder

Panic disorder (PD) is a common anxiety disorder. Despite neurophysiological advances, its pathogenesis is still not well elucidated. Although the recommended pharmacological agents have demonstrated efficacy and a rather acceptable tolerability, yet many patients do not respond fully and still suffer from residual symptoms. There is a need for new pharmacological classes with better tolerability and efficacy, and faster onset of action. The purpose of this review is to illustrate the existing non-antidepressant treatment of PD as well as the recent advances in the treatment of PD. 38 articles discussing pharmacological treatment of PD were selected for this review. They were mainly openlabel studies, case-reports and review articles. We reviewed the studies on anticonvulsants, benzodiazepines, gamma amino butyric acid (GABAergic) products, atypical antipsychotics, clonidine, as well as emerging drugs in the treatment of PD such as metabotropic glutamate II agonists, and D-cycloserine. Although most of the drugs tested were proven effective and well tolerated, the studies on the nonconventional agents are restricted to open-label trials and case reports. Further studies are required to establish their efficacy and tolerability in the treatment of panic disorder.

Antidepressant drug action--From rapid changes on network function to network rewiring.

There has been significant recent progress in understanding the neurobiological mechanisms of antidepressant treatments. The delayed-onset of action of monoamine-based antidepressant drugs have been associated to their ability to slowly increase synaptic plasticity and neuronal excitability via altering neurotrophic signaling (synthesis of BDNF and activation of its receptor TrkB), dematuration of GABAergic interneurons and inhibition of "breaks of plasticity". On the other hand, antidepressants rapidly regulate emotional processing that - with the help of heightened plasticity and appropriate rehabilitation - gradually lead to significant changes on functional neuronal connectivity and clinical recovery. Moreover, the discovery of rapid-acting antidepressants, most notably ketamine, has inspired interest for novel antidepressant developments with better efficacy and faster onset of action. Therapeutic effects of rapid-acting antidepressants have been linked with their ability to rapidly regulate neuronal excitability and thereby increase synaptic translation and release of BDNF, activation of the TrkB-mTOR-p70S6k signaling pathway and increased synaptogenesis within the prefrontal cortex. Thus, alterations in TrkB signaling, synaptic plasticity and neuronal excitability are shared neurobiological phenomena implicated in antidepressant responses produced by both gradually and rapid acting antidepressants. However, regardless of antidepressant, their therapeutic effects are not permanent which suggests that their effects on neuronal connectivity and network function remain unstable and vulnerable for psychosocial challenges.

Pharmacokinetic studies for proving bioequivalence of orally inhaled drug products-critical issues and concepts.

OPINION article Front. Pharmacol., 03 June 2015Sec. Experimental Pharmacology and Drug Discovery https://doi.org/10.3389/fphar.2015.00117

Neuromodulation therapies for geriatric depression.

Depression is frequent in old age and its prognosis is poorer than in younger populations. The use of pharmacological treatments in geriatric depression is limited by specific pharmacodynamic age-related factors that can diminish tolerability and increase the risk of drug interactions. The possibility of modulating cerebral activity using brain stimulation techniques could result in treating geriatric depression more effectively while reducing systemic side effects and medication interactions. This may subsequently improve treatment adherence and overall prognosis in the older patient. Among clinically available neuromodulatory techniques, electroconvulsive therapy (ECT) remains the gold standard for the treatment of severe depression in the elderly. Studies have proven that ECT is more effective and has a faster onset of action than antidepressants in the treatment of severe, unipolar, geriatric depression and that older age is a predictor of rapid ECT response and remission. The application of novel and more tolerable forms of ECT for geriatric depression is currently being examined. Preliminary results suggest that right unilateral ultrabrief ECT (RUL-UB ECT) is a promising intervention, with similar efficacy to brief-pulse ECT and fewer adverse cognitive effects. Overall findings in repetitive transcranial magnetic stimulation (rTMS) suggest that it is a safe intervention in geriatric depression. Higher rTMS stimulation intensity and more treatments may need to be given in the elderly to achieve optimal results. There is no specific data on vagus nerve stimulation in the elderly. Transcranial direct current stimulation, magnetic seizure therapy and deep brain stimulation are currently experimental, and more data from geriatric samples is needed.

Pharmacological assessment of the onset of action of aclidinium and glycopyrronium versus tiotropium in COPD patients and human isolated bronchi

Preclinical studies suggested that aclidinium and glycopyrronium might have a faster onset of action than tiotropium. In this study we assessed the onset of action of aclidinium and glycopyrronium versus tiotropium, all administered at the approved clinical doses, in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD) and in human isolated bronchi by using different concentrations. Sixteen COPD patients inhaled single doses of aclidinium 400µg, glycopyrronium 50μg and tiotropium 18µg and FEV1 was measured to assess their onset of action. In human isolated bronchi the time to evoke half maximal relaxation of transmural stimulation was tested from 10nM to 1µM for each drug. Nine, eight and twelve patients did not achieve 15% increase of FEV1 after inhalation of aclidinium, glycopyrronium and tiotropium, respectively. Aclidinium (15.6±7.5min) and glycopyrronium (17.9±10.4min) enhanced 15% FEV1 more rapidly than tiotropium (42.5±19.4min), with no significant difference (P>0.05). In isolated airways, glycopyrronium elicited a dose-dependent onset of action (10nM: 8.2±1.3min, 100nM: 7.1±2.1min, 1μM: 3.4±0.4min) that was faster compared to that induced by aclidinium (1μM: 6.4±0.5min) and tiotropium (1μM: 8.4±1.1min) (P<0.05), that halved the contractile tone only at the highest concentration. Bronchodilation induced by aclidinium and glycopyrronium was faster than that induced by tiotropium, but since our analysis was restricted to the acute effect of these LAMAs and the inhaled doses were not isoeffective, the real differences in their impact on the onset of bronchodilation will be definitely determined after a long-term challenge of these treatments at isoeffective doses in COPD patients.

AVP-825 Produces Effective, Well-Tolerated Migraine Relief

AVP-825 is a product containing a low-dose powder form of sumatriptan that can be delivered intranasally to treat migraines. It is better tolerated than higher doses of oral sumatriptan and has a faster onset of action. A pooled analysis of 2 studies confirmed that AVP-825 confers rapid headache relief sustained over 48 hours.

An extraordinary relationship involving MIF-1 and other peptides

In commemoration of Abba J. Kastin's exceptional service as the founding editor for the international journal Peptides, I review our collaborative work on how neuropeptides are involved in depression and other neuropsychiatric behavior. A special focus is on MIF-1 (prolyl-leucyl-glycinamide) that was discovered in the Kastin laboratory and shown effective to treat human depression with greater efficacy and faster onset of action than traditional antidepressants at the time of clinical trial. My personal reflection of the evolving changes of translational research on neuropeptides will hopefully provide some insight to young investigators.

Clinical efficacy and safety of Vitaros©/Virirec© (Alprostadil cream) for the treatment of erectile dysfunction.

Erectile dysfunction (ED) is a very common disorder with a deep impact on patients and their partners. Several options are now available for treating ED; oral pharmacotherapy with phosphodiesterase-5 (PDE5) inhibitors currently represents the first-line option for many ED patients. Vitaros©/Virirec© is new topical, non-invasive treatment for ED that offers the combination of an active drug (alprostadil, a synthetic PGE1) with a skin enhancer that improves its local absorption directly at the site of action. Vitaros©/Virirec© has a favorable pharmacodynamic profile and is poorly absorbed in systemic circulation. This makes it suitable in any circumstances and results in a reduced risk of adverse events (AEs), being systemic AEs reported in only 3% of the treated population. Its clinical efficacy has been demonstrated in both phase II and III trials, showing a global efficacy up to 83% with the 300 μg dose in patients with severe ED significantly better than placebo. Its fast onset of action together with its favorable toxicity profile and lack of interactions with other drugs makes Vitaros©/Virirec© a first-line therapeutic option for patients with ED, particularly for individuals who are reluctant to take systemic treatments or with AEs. It may also have an important role in patients not responding to PDE5 inhibitors, particularly those with ED after radical prostatectomy.

Ticagrelor: A Review of Its Use in Adults with Acute Coronary Syndromes

Ticagrelor (Brilique™, Brilinta®), a cyclopentyl-triazolopyrimidine, is an orally active, reversible, and selective adenosine diphosphate (ADP) receptor antagonist indicated for use in patients with acute coronary syndromes (ACS). Ticagrelor has a faster onset of action and provides greater inhibition of platelet aggregation than clopidogrel. In the large well-designed, PLATO study in adult patients with ACS, 12 months' treatment with ticagrelor was more effective than clopidogrel in reducing the incidence of the primary composite endpoint of myocardial infarction, stroke, or cardiovascular (CV) death. Ticagrelor also reduced all-cause mortality relative to clopidogrel, although statistical significance of this was not confirmed in hierarchical testing. Benefit with ticagrelor was seen both in invasively and noninvasively managed patients. Ticagrelor was generally well tolerated and was not associated with an increased risk of major bleeding relative to clopidogrel. However, the incidences of non-coronary artery bypass grafting (CABG)-related bleeding, and major or minor bleeding, as well as some non-hemorrhagic adverse events, including dyspnea (usually of mild or moderate severity) and ventricular pauses (largely asymptomatic) were higher with ticagrelor. In addition, the ATLANTIC study showed that although pre-hospital administration of ticagrelor did not improve pre-percutaneous coronary intervention (PCI) coronary reperfusion in ACS patients relative to in-hospital administration, ticagrelor was safe in both instances, with no significant between-group differences in non-CABG-related major and minor bleeding events. Although further comparative studies with other antiplatelet agents, including prasugrel, are required to position it more definitively, current evidence indicates that ticagrelor is a useful option for the prevention of thrombotic CV events in ACS patients managed invasively or noninvasively.

Design, Development and Optimization Aceclofenac Effervescence tablets by Central Composite Design

The oral solid dosage forms are the most popular way of taking medication despite having some disadvantages like slow absorption and hence prolong onset of action. These problems can be overcome by some drug delivery system like mouth dissolving tablets, dispersible tablets, effervescent tablets, etc. Aceclofenac is often used to relieve the inflammation, swelling, stiffness and joint pain which sometimes required fast onset of action. Aceclofenac effervescent tablet was prepared to enhance onset of action. Tablets were prepared using anhydrous citric acid, tartaric acid and effersoda as effervescent components by direct compression method. Solid dispersion of Aceclofenac with anhydrous lactose can be prepared to increase solubility of aceclofenac. The solid dispersions were evaluated for drug content, practical yield, solubility and DSC for drug complex study. Central composite design was used for optimization of aceclofenac effervescent tablet. The effervescent formulations were evaluated for physicochemical parameters, drug content, effervescent lag time, total effervescent time, in vitro drug release study, FTIR for compatibility and stability testing. Optimized formula showed more than 50% drug release after 5 min and hence faster onset of action. The study point of aceclofenac effervescent tablet is ease of administration, accuracy of dosing and faster onset of action.

In vitro and in vivo evaluation of fast-dissolving tablets containing solid dispersion of lamotrigine.

Aim:Investigation of in vitro/in vivo behavior of fast-dissolving tablets containing solid dispersions (SDs) of lamotrigine (LM) was the aim and focus of the present research work.Material and Methods:The effect of various hydrophilic polymers on the aqueous solubility of LM was studied. Polyethylene glycol (PEG 6000) was selected as the vehicle and SDs were prepared by melting and solvent evaporation method (SEM). Evaluation of SD for dissolution indicated SVM was more appropriate as seen from an enhancement in drug dissolution. Infrared spectroscopy, differential scanning calorimetry, and powder X-ray diffraction studies indicated a lack of physicochemical interaction between the drug and the carrier. A total of nine formulations were compressed into fast-dissolving tablets using Avicel pH 102 as a directly compressible filler and ac-di-sol, sodium starch glycolate and crospovidone as super disintegrates and evaluated for pre- and post-compression parameters and in vitro drug release.Results:Mathematical analysis of in vitro data suggested that first order was most suitable mathematical model for describing the optimized formulation. Stability studies indicated that the effect of storage was insignificant at 5% level of confidence. In vivo studies of pure drug, selected formulation and marketed product were carried out in male Wistar rats and pharmacokinetic (PK) parameters were calculated using PK function for Microsoft Excel. The best formulation has shown Tmax of 0.5 h which was highly significant (P < 0.05) when compared with pure drug and marketed formulation. The statistical significance was assessed by one way analysis of variance.Conclusion:Therefore, the SDs prepared by SEM using PEG 6000 as hydrophilic carrier can be successfully used for improvement of dissolution of LM and resulted in faster onset of action as indicated by in vivo studies.

A Current Review on Orodispersible Tablet

The convenience of administration and improved patient compliance are important in the design of oral drug delivery system which remains the preferred route of drug delivery. Oral drug delivery is a one of the simplest routes of delivery of drugs for systemic and in certain cases local effect. Certain disease has sudden attacks and need immediate relief. Orodispersible tablets are solid dosage forms which dissolve rapidly in saliva without chewing and give fast onset of action. Orodispersible tablets overcome the disadvantages of conventional dosage form especially dysphasia (difficulty in swallowing) in paediatric and geriatric patients and it needs no water which is also convenient during travelling. The article describes the advantages and disadvantages of ODTs, critical step during formulation, mechanisms of disintegration, the popular methods used to produce large scale tablets for commercial purpose, evaluation parameters.

In Vitro/In Vivo Evaluation and Bioavailability Study of Amitriptyline Hydrochloride from the Optimized Oral Fast Dissolving Films

The present investigation was undertaken with the objective of developing fast dissolving film(s) of a tricyclic antidepressant drug amitriptyline hydrochloride in order to improve its bioavailability, optimize its therapeutic action especially when used to treat major depression and to enhance the compliance for the developmentally disable, mentally ill, elderly and pediatric patients. Fast dissolving dosage forms have acquired great importance in pharmaceutical industry because of their unique properties. Ten formulations were prepared by solvent casting method using different polymer types, plasticizer types, surfactant concentrations and different ratio of hydroxypropyl methyl cellulose and maltodextrin. The prepared films were evaluated for folding endurance, thickness, drug content, in vitro/in vivo disintegration time, drug release and tensile test. The optimized formula F8 containing HPMC 15cp and maltodextrin in 1:1 ratio showed minimum in vitro/in vivo disintegration time 16.8, 13.2 seconds respectively, highest dissolution rate i.e. T80% 1.1 minutes, D2 min (%) 89.77% and satisfactory mechanical properties. The optimized film was further evaluated for bioavailability compared with a marketed solution (Amitriptyline Hydrochloride®), the study based on cross over design using experimental animals (rabbits). The pharmacokinetic results revealed that the fast dissolving films has higher peak blood concentration (Cmax, 0.927µg/ml) within shorter time (Tmax, 2 hours), indicating rapid absorption and faster onset of action with acceptable bioavailability value. These findings suggest that the fast dissolving film containing amitriptyline hydrochloride is expected to become one of choices for the treatment of acute depression.

Glycopyrronium for chronic obstructive pulmonary disease: evidence and rationale for use from the GLOW trials

The clinical development of the long-acting muscarinic antagonist bronchodilator glycopyrronium (Seebri® Breezhaler® inhalation powder) in the GLOW (glycopyrronium bromide in chronic obstructive pulmonary disease airways) series of studies showed that, compared with placebo, once-daily glycopyrronium provided 24-h bronchodilation, improved symptoms and health status and reduced the risk and rate of moderate or severe exacerbations. Glycopyrronium also reduced dynamic hyperinflation and increased exercise tolerance. Compared with the long-acting muscarinic antagonist tiotropium, glycopyrronium had a similar effect on clinical outcomes with a faster onset of action. Added to the long-acting β2-agonist bronchodilator indacaterol, glycopyrronium had a greater bronchodilator effect and improved dyspnea versus indacaterol alone. There were no significant safety issues in the GLOW studies. Glycopyrronium is a useful addition to the treatments for chronic obstructive pulmonary disease.

Nebulized Therapy. SEPAR Year

Inhaled drugs are deposited directly in the respiratory tract. They therefore achieve higher concentrations with faster onset of action and fewer side effects than when used systemically. Nebulized drugs are mainly recommended for patients that require high doses of bronchodilators, when they need to inhale drugs that only exist in this form (antibiotics or dornase alfa) or when they are unable to use other inhalation devices. Technological development in recent years has led to new devices that optimize pulmonary deposits and reduce the time needed for treatment. In this review we focus solely on drugs currently used, or under investigation, for nebulization in adult patients, basically bronchodilators, inhaled steroids, antibiotics, antifungals, mucolytics and others such as anticoagulants, prostanoids, and lidocaine.

In vitro‐in vivo performance evaluation of treated Plantago ovata husk based fast dissolving tablets of glipizide: Flashtab technology

Physicians suggest premeal administration of glipizide (30 min before a meal) because of longer disintegration time (approximately 15 min) of conventional tablet. Hence, the dosage form was developed, called as fast dissolving tablet (FDT), which disintegrates rapidly within a minute. FDTs by Flashtab technology is based on a swellable agent and a superdisintegrant. In the current study, treated Plantago ovata husk (TPOH), and microcrystalline cellulose were utilized as natural superdisintegrant and swellable agent, respectively. FDT formulations were prepared by direct compression and evaluated for in vitro tablet performance, such as disintegration time, wetting time, hardness, friability, swelling and percent drug release. On the basis of finding, formulation with 15% TPOH concentration (TPOH 7) was selected as optimized formulation. To evaluate the in vitro performance, the formulation TPOH 7 and the marketed tablets (glynase) were administered to rabbits. In the case of marketed tablet, the peak plasma‐concentration of glipizide was obtained in 2.83 h of administration whereas it was 2 h for TPOH 7 indicating immediate absorption and therefore faster onset of action of the prepared FDT formulation than the marketed one. Drug interaction studies, performed by using FTIR spectroscopy, X‐ray diffractometry and differential scanning calorimetric methods, indicate that the glipizide is compatible with the formulation components. The accelerated stability study (40°C ± 2°C/75% ±5% relative humidity) for the optimized formulation showed a negligible change over time for the in vitro parameters. The results suggest that TPOH has promising potential for faster disintegration and fulfills the requirement of FDTs. Key words: Direct compression, fast dissolving tablets, flashtab technology, glipizide, Plantago ovata husk, superdisintegrant

Aclidinium bromide for stable chronic obstructive pulmonary disease.

Bronchodilators are the mainstay for symptom relief in the management of stable chronic obstructive pulmonary disease (COPD). Aclidinium bromide is a new long-acting muscarinic antagonist (LAMA) that differs from tiotropium by its higher selectivity for M3 muscarinic receptors with a faster onset of action. However, the duration of action of aclidinium is shorter than for tiotropium. It has been approved as maintenance therapy for stable, moderate to severe COPD, but its efficacy and safety in the management of COPD is uncertain compared to other bronchodilators. To assess the efficacy and safety of aclidinium bromide in stable COPD. We identified randomised controlled trials (RCT) from the Cochrane Airways Group Specialised Register of trials (CAGR), as well as www.clinicaltrials.gov, World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), US Food and Drug Administration (FDA) website and Almirall Clinical Trials Registry and Results. We contacted Forest Laboratories for any unpublished trials and checked the reference lists of identified articles for additional information. The last search was performed on 7 April 2014 for CAGR and 11 April 2014 for other sources. Parallel-group RCTs of aclidinium bromide compared with placebo, long-acting beta2-agonists (LABA) or LAMA in adults with stable COPD. Two review authors independently selected studies, assessed the risk of bias, and extracted data. We sought missing data from the trial authors as well as manufacturers of aclidinium. We used odds ratios (OR) for dichotomous data and mean difference (MD) for continuous data, and reported both with their 95% confidence intervals (CI). We used standard methodological procedures expected by The Cochrane Collaboration. We applied the GRADE approach to summarise results and to assess the overall quality of evidence. This review included 12 multicentre RCTs randomly assigning 9547 participants with stable COPD. All the studies were industry-sponsored and had similar inclusion criteria with relatively good methodological quality. All but one study included in the meta-analysis were double-blind and scored low risk of bias. The study duration ranged from four weeks to 52 weeks. Participants were more often males, mainly Caucasians, mean age ranging from 61.7 to 65.6 years, and with a smoking history of 10 or more pack years. They had moderate to severe symptoms at randomisation; the mean post-bronchodilator forced expiratory volume in one second (FEV1) was between 46% and 57.6% of the predicted normal value, and the mean St George's Respiratory Questionnaire score (SGRQ) ranged from 45.1 to 50.4 when reported.There was no difference between aclidinium and placebo in all-cause mortality (low quality) and number of patients with exacerbations requiring a short course of oral steroids or antibiotics, or both (moderate quality). Aclidinium improved quality of life by lowering the SGRQ total score with a mean difference of -2.34 (95% CI -3.18 to -1.51; I(2) = 48%, 7 trials, 4442 participants) when compared to placebo. More patients on aclidinium achieved a clinically meaningful improvement of at least four units decrease in SGRQ total score (OR 1.49; 95% CI 1.31 to 1.70; I(2) = 34%; number needed to treat (NNT) = 10, 95% CI 8 to 15, high quality evidence) over 12 to 52 weeks than on placebo. Aclidinium also resulted in a significantly greater improvement in pre-dose FEV1 than placebo with a mean difference of 0.09 L (95% CI 0.08 to 0.10; I(2) = 39%, 9 trials, 4963 participants). No trials assessed functional capacity. Aclidinium reduced the number of patients with exacerbations requiring hospitalisation by 4 to 20 fewer per 1000 over 4 to 52 weeks (OR 0.64; 95% CI 0.46 to 0.88; I(2) = 0%, 10 trials, 5624 people; NNT = 77, 95% CI 51 to 233, high quality evidence) compared to placebo. There was no difference in non-fatal serious adverse events (moderate quality evidence) between aclidinium and placebo.Compared to tiotropium, aclidinium did not demonstrate significant differences for exacerbations requiring oral steroids or antibiotics, or both, exacerbation-related hospitalisations and non-fatal serious adverse events (very low quality evidence). Inadequate data prevented the comparison of aclidinium to formoterol or other LABAs. Aclidinium is associated with improved quality of life and reduced hospitalisations due to severe exacerbations in patients with moderate to severe stable COPD compared to placebo. Overall, aclidinium did not significantly reduce mortality, serious adverse events or exacerbations requiring oral steroids or antibiotics, or both.Currently, the available data are insufficient and of very low quality in comparisons of the efficacy of aclidinium versus tiotropium. The efficacy of aclidinium versus LABAs cannot be assessed due to inaccurate data. Thus additional trials are recommended to assess the efficacy and safety of aclidinium compared to other LAMAs or LABAs.

Symptomatic intracerebral hemorrhage in acute ischemic stroke after thrombolysis with intravenous recombinant tissue plasminogen activator: a review of natural history and treatment.

Intravenous thrombolysis remains the mainstay treatment for acute ischemic stroke. One of the most feared complications of the treatment is thrombolysis-related symptomatic intracerebral hemorrhage (sICH), which occurs in nearly 6% of patients and carries close to 50% mortality. The treatment options for sICH are based on small case series and expert opinion, and the efficacy of recommended treatments is not well known. To provide an overview on the rationale and mechanism of action of potential treatments for sICH that may reverse the coagulopathy before hematoma expansion occurs. Evidence-based peer-reviewed articles, including randomized trials, case series and reports, and retrospective reviews, were identified in a PubMed search on the mechanism of action of intravenous recombinant tissue plasminogen activator and the rationale of various potential treatments using the coagulation cascade as a model. The search encompassed articles published from January 1, 1990, through February 28, 2014. The current treatments may not be sufficient to reverse coagulopathy early enough to prevent hematoma expansion and improve the outcome of thrombolysis-related hemorrhage. Given the mechanism of action of intravenous recombinant tissue plasminogen activator, clinical studies could include agents with a fast onset of action, such as prothrombin complex concentrate, recombinant factor VIIa, and ε-aminocaproic acid, as potential therapeutic options.