Potential Add-on Therapy Research Articles

Nebulized alteplase in coronavirus disease 2019 pneumonia: a case series

BackgroundMany patients with severe coronavirus disease 2019 pneumonia exhibit signs of microthrombosis. Previous studies discussed intravenous fibrinolytic agents as potential add-on therapy in these patients. Therefore, we propose the inhalative administration of fibrinolytics as a possible safer alternative.Case presentationThis case series describes five white male patients, aged 51–78 years, treated with off-label inhalation of alteplase between November and December 2020. All patients suffered from severe severe acute respiratory syndrome coronavirus 2 infection with respiratory failure. Pulmonary embolism was ruled out by pulmonary angiogram in computed tomography scans, and all patients showed signs of coronavirus disease 2019 pneumonia. Four patients improved clinically, while one patient with advanced chronic diseases died due to multiple organ failure. No directly associated adverse effects were observed following inhalation of alteplase.ConclusionThis case series warrants further attention to investigate inhalative alteplase as an additional treatment in patients with severe coronavirus disease 2019 infection.

Investigation of mesalazine as an antifibrotic drug following myocardial infarction in male mice.

Myocardial infarction (MI) initiates a complex reparative response during which damaged cardiac muscle is replaced by connective tissue. While the initial repair is essential for survival, excessive fibrosis post-MI is a primary contributor to progressive cardiac dysfunction, and ultimately heart failure. Currently, there are no approved drugs for the prevention or the reversal of cardiac fibrosis. Therefore, we tested the therapeutic potential of repurposed mesalazine as a post-MI therapy, as distinct antifibrotic effects have recently been demonstrated. At 8 weeks of age, MI was induced in male C57BL/6J mice by LAD ligation. Mesalazine was administered orally at a dose of 100 μg/g body weight in drinking water. Fluid intake, weight development, and cardiac function were monitored for 28 days post intervention. Fibrosis parameters were assessed histologically and via qPCR. Compared to controls, mesalazine treatment offered no survival benefit. However, no adverse effects on heart and kidney function and weight development were observed, either. While total cardiac fibrosis remained largely unaffected by mesalazine treatment, we found a distinct reduction of perivascular fibrosis alongside reduced cardiac collagen expression. Our findings warrant further studies on mesalazine as a potential add-on therapy post-MI, as perivascular fibrosis development was successfully prevented.

Gut Microbial Metabolite Butyrate and Its Therapeutic Role in Inflammatory Bowel Disease: A Literature Review.

Background and objective: Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is a chronic inflammatory disorder characterized by aberrant immune responses and compromised barrier function in the gastrointestinal tract. IBD is associated with altered gut microbiota and their metabolites in the colon. Butyrate, a gut microbial metabolite, plays a crucial role in regulating immune function, epithelial barrier function, and intestinal homeostasis. In this review, we aim to present an overview of butyrate synthesis and metabolism and the mechanism of action of butyrate in maintaining intestinal homeostasis and to discuss the therapeutic implications of butyrate in IBD. Methods: We searched the literature up to March 2023 through PubMed, Web of Science, and other sources using search terms such as butyrate, inflammation, IBD, Crohn's disease, and ulcerative colitis. Clinical studies in patients and preclinical studies in rodent models of IBD were included in the summary of the therapeutic implications of butyrate. Results: Research in the last two decades has shown the beneficial effects of butyrate on gut immune function and epithelial barrier function. Most of the preclinical and clinical studies have shown the positive effect of butyrate oral supplements in reducing inflammation and maintaining remission in colitis animal models and IBD patients. However, butyrate enema showed mixed effects. Butyrogenic diets, including germinated barley foodstuff and oat bran, are found to increase fecal butyrate concentrations and reduce the disease activity index in both animal models and IBD patients. Conclusions: The current literature suggests that butyrate is a potential add-on therapy to reduce inflammation and maintain IBD remission. Further clinical studies are needed to determine if butyrate administration alone is an effective therapeutic treatment for IBD.

An Integrative Approach to Investigate the Mode of Action of (-)-Dendroparishiol in Bacterial Meningitis: Computer-Aided Estimation of Biological Activity and Network Pharmacology.

Bacterial meningitis remains one of the most prevalent infectious diseases worldwide. Although advances in medical care have improved mortality and morbidity, neurological complications remain high. Therefore, aside from antibiotics, therapeutic adjuvants targeting neuroinflammation are essential to combat the long-term neuronal sequelae of bacterial meningitis. In the present study, we propose (-)-dendroparishiol as a potential add-on therapy to improve neuroinflammation associated with bacterial meningitis. The biological activity of (-)-dendroparishiol was first predicted by computational analysis and further confirmed in vitro using a cell-based assay with LPS-induced BV-2 microglial cells. Biological pathways involved with (-)-dendroparishiol were identified by applying network pharmacology. Computational predictions of biological activity indicated possible attenuation of several inflammatory processes by (-)-dendroparishiol. In LPS-induced BV-2 microglial cells, (-)-dendroparishiol significantly reduced the expression of inflammatory mediators: iNOS, NO, COX-2, IL-6, and TNF-α. Molecular docking results demonstrated the potential iNOS and COX-2 inhibitory activity of (-)-dendroparishiol. Network pharmacological analysis indicated the plausible role of (-)-dendroparishiol in biological processes involved in oxidative stress and neuroinflammation with enrichment in neuroinflammatory pathways. Overall, this study provides scientific evidence for the potential application of (-)-dendroparishiol in the management of bacterial meningitis-associated neuroinflammation.

The Synthetic Flavonoid Hidrosmin Improves Endothelial Dysfunction and Atherosclerotic Lesions in Diabetic Mice.

In diabetes, chronic hyperglycemia, dyslipidemia, inflammation and oxidative stress contribute to the progression of macro/microvascular complications. Recently, benefits of the use of flavonoids in these conditions have been established. This study investigates, in two different mouse models of diabetes, the vasculoprotective effects of the synthetic flavonoid hidrosmin on endothelial dysfunction and atherogenesis. In a type 2 diabetes model of leptin-receptor-deficient (db/db) mice, orally administered hidrosmin (600 mg/kg/day) for 16 weeks markedly improved vascular function in aorta and mesenteric arteries without affecting vascular structural properties, as assessed by wire and pressure myography. In streptozotocin-induced type 1 diabetic apolipoprotein E-deficient mice, hidrosmin treatment for 7 weeks reduced atherosclerotic plaque size and lipid content; increased markers of plaque stability; and decreased markers of inflammation, senescence and oxidative stress in aorta. Hidrosmin showed cardiovascular safety, as neither functional nor structural abnormalities were noted in diabetic hearts. Ex vivo, hidrosmin induced vascular relaxation that was blocked by nitric oxide synthase (NOS) inhibition. In vitro, hidrosmin stimulated endothelial NOS activity and NO production and downregulated hyperglycemia-induced inflammatory and oxidant genes in vascular smooth muscle cells. Our results highlight hidrosmin as a potential add-on therapy in the treatment of macrovascular complications of diabetes.

Lactobacillus crispatus M247: Characteristics of a Precision Probiotic Instrument for Gynecological and Urinary Well-Being

The altered patterns of a microbial population colonizing an organ are increasingly recognized as a relevant item in human disease pathogenesis. The female urogenital tract is no exception, as some vaginal microbiota patterns, named community state types (CSTs), and urinary tract microbiota patterns, named urotypes (UTs), have been linked to viral, inflammatory, and gestational diseases. Treating these conditions is an issue, as antibiotic therapies alone are not always effective. Lactobacillus crispatus M247 is a strain with good intestinal and vaginal adhesion capability, combined with local antibacterial and anti-inflammatory properties; this strain also has proven nontransferable resistance to antibiotics commonly used in female genital tract infections, such as metronidazole. Lactobacillus crispatus M247 could, therefore, be considered as a potential add-on therapy to antibiotics in vaginal tract infections, with the aim to restore a favorable microbiota pattern.

Efficacy and Safety of Dipeptidyl Peptidase-4 Inhibitor Compared to Sulphonylurea in Type II Diabetes Patients Inadequately Controlled with Metformin Alone

INTRODUCTIONDiabetes is a metabolic disorder marked by high blood glucose levels, and treatment often requires multiple drugs to achieve adequate glycemic control. In individuals with type 2 diabetes mellitus who do not respond to Metformin, doctors may prescribe a Dipeptidyl Peptidase-4 inhibitor or a Sulphonylurea as potential add-on therapy. The study was conducted to compare the efficacy and safety of the Dipeptidyl Peptidase-4 inhibitor with Sulphonylurea. MATERIAL AND METHODSThis was an interventional, comparative study involving 100 type 2 diabetic patients who visited the Medicine department at Universal college of Medical Sciences. All the eligible patients were randomly divided into two treatment groups (50 each): Group A (Sulphonylurea + Metformin) and Group B (Dipeptidyl Peptidase-4 inhibitor + Metformin). Treatment was provided for 18 weeks, and patients were investigated for blood glucose parameters like glycosylated hemoglobin, fasting blood glucose, postprandial glucose at baseline and after 18 weeks of follow-up, and questions regarding adverse reactions. The efficacy of the drugs between the two treatment groups was compared using an independent t-test. RESULTSDipeptidyl Peptidase-4 inhibitor plus Metformin was found to be superior to Sulphonylurea plus Metformin in terms of HbA1c-lowering efficacy (p=0.030). A total of 26% of patients in the Sulphonylurea group reported unpleasant hypoglycemic events, compared to 6% in the Dipeptidyl Peptidase-4 inhibitor group (p=0.006). Patients treated with Sulphonylurea gained weight over 18 weeks, but those on Dipeptidyl Peptidase-4 inhibitor lost weight (p=0.043). CONCLUSIONCompared to Sulphonylurea, adding a Dipeptidyl Peptidase-4 inhibitor to a Metformin therapy significantly improves glycaemic control in type 2 diabetic patients who are not well controlled with Metformin monotherapy, without producing hypoglycemia or weight gain.

Antihyperglycemic Activity of Syzygium cumini (Jamun) in Diabetic Rats

Background: Recently with the changes in population lifestyle, prediabetes is constantly on the rise. Management of prediabetes currently is with lifestyle modifications like weight loss, exercise and diet control. Better drugs with acceptable safety profile are needed for better control of prediabetes. This study was thus designed to evaluate the antihyperglycaemic effect of one such potential compound Syzygium cumini (SC) (Jamun)in comparison to conventional antidiabetic drug Metformin.
 Methods: Rats were divided into four study groups (SC 100mg/kg and 200 mg/kg, metformin 90 mg/kg and SC 200 mg/kg with metformin 90 mg/kg). The glycaemic changes were followed up for a period of 8 weeks.
 Results: Streptozotocin (STZ) induced significant rise in blood glucose levels in the rats. SC100 mg/kg and 200 mg/kg caused a reduction in BSL (192.50 ± 6.189 & 175.00 ± 6.782 respectively). SC 200 mg/kg alone and in combination with metformin caused a significant reduction in HbA1C levels at the end of 8th week (8.84 ± 0.65 &6.86 ± 0.40 respectively) as compared to their baseline levels. Increase in dose had led to more significant reduction in BSL at the end of 8th week in groups A & B (p < 0.05). However, reduction of BSL was superior with Metforminalone (159.17 ± 13.060) compared to Syzygium cumini administered alone. Also antihyperglycemic effect of Syzygium cumini administered along with metformin was significant (p < 0.05) compared to either doses of Syzygium cumini given alone.
 Conclusions: Syzygium cumini demonstratedantihyperglycemic activity in diabetic rats but less significant when compared to metformin. Antihyperglycaemic effect of Syzygium cumini with metformin was significantly better than either drugsgiven alone. In prediabetic or diabeticindividuals Syzygium cumini seed powdercan be suggested as a potential add-on therapy with conventional antidiabetic drugs. However more non-clinical and clinical studies need to be conducted to confirm the findings.

Liraglutide reduces hyperglycaemia and body weight in overweight, dysregulated insulin-pump-treated patients with type 1 diabetes: The Lira Pump trial-a randomized, double-blinded, placebo-controlled trial.

To investigate the efficacy of adding the glucagon-like peptide-1 receptor agonist liraglutide to continuous subcutaneous insulin infusion (CSII) in overweight or obese persons with type 1 diabetes and non-optimal glycaemic control. A 26-week, randomized, double-blind, placebo-controlled trial including 44 overweight or obese adults with type 1 diabetes randomized 1:1 to liraglutide 1.8 mg once daily (QD) or placebo added to CSII treatment. The primary endpoint was change in haemoglobin A1c (HbA1c). Secondary endpoints included change in insulin dose, CSII settings, glycaemic variability, body weight and patient-reported outcome measures. Finally, adverse effects including hypoglycaemic events were registered. HbA1c was reduced by 5 mmol/mol (0.5%) from a baseline of 66 mmol/mol (8.2%) in patients treated with liraglutide compared with a non-significant change of +2.3 mmol/mol (0.2%) from a baseline of 66 mmol/mol (8.1%) in patients treated with placebo (between-group difference 7 mmol/mol [0.7%], P < 0.001). Liraglutide reduced total insulin dose by 8 units/day or 16% of total insulin dose (P = 0.008). Mean body weight was reduced by 6.3 kg (P < 0.001) compared with placebo. Concomitantly, time spent in glycaemic target range 4-10 mmol/L (71-180 mg/dL) increased while the risk of hypoglycaemia did not differ between groups at the end of treatment. Liraglutide treatment reduced HbA1c, total daily insulin dose and body weight without increasing the risk of hypoglycaemia in CSII-treated patients with type 1 diabetes and insufficient glycaemic control. Liraglutide may be considered a potential add-on therapy to insulin in this subgroup of patients.

Impaired chloride homeostasis in epilepsy: Molecular basis, impact on treatment, and current treatment approaches.

Epilepsies represent one of the most common neurological diseases worldwide. They are characterized by recurrent spontaneous seizures with severe impact on a patient's life. An imbalance in excitatory and inhibitory signalling is considered the main underlying pathophysiological mechanism. Therefore, GABA-mimetic drugs, strengthening the main inhibitory signalling system in the CNS, are frequently used as antiepileptic or anticonvulsant drugs. However, the therapeutic effect of such treatment depends on the chloride gradient along the plasma membrane. Impairment of chloride homeostasis, caused by alterations in the functional balance of chloride transporters, was implicated in the pathophysiology of epilepsy and numerous other diseases. Breakdown or even inversion of the chloride gradient may result in ineffective or in worst cases proconvulsant effects of GABA-mimetics. Unfortunately, such situations are reported in considerable number. Consequently, bumetanide, an inhibitor of Na-K-Cl cotransporters gained interest as potential add-on therapy re-establishing the chloride gradient and thereby the hyperpolarizing effects of GABA-mimetic drugs. Indeed, preclinical studies yielded encouraging results, especially when applied in combination with GABA-mimetics in epilepsy models. However, bumetanide induces a strong diuretic effect and displays poor penetration across the blood-brain barrier, two adverse features for chronic antiepileptic treatment. Therefore, new compounds overcoming these limitations are under development. This review focuses on alterations in chloride homeostasis and its underlying molecular mechanisms in epilepsy, on the potential impact of impaired chloride homeostasis on the treatment of epilepsy and on concepts to overcome this problem including recent development of bumetanide derivatives with improved pharmacological profile.

Does Fractional Anisotropy Predict Motor Imagery Neurofeedback Performance in Healthy Older Adults?

Motor imagery neurofeedback training has been proposed as a potential add-on therapy for motor impairment after stroke, but not everyone benefits from it. Previous work has used white matter integrity to predict motor imagery neurofeedback aptitude in healthy young adults. We set out to test this approach with motor imagery neurofeedback that is closer to that used for stroke rehabilitation and in a sample whose age is closer to that of typical stroke patients. Using shrinkage linear discriminant analysis with fractional anisotropy values in 48 white matter regions as predictors, we predicted whether each participant in a sample of 21 healthy older adults (48–77 years old) was a good or a bad performer with 84.8% accuracy. However, the regions used for prediction in our sample differed from those identified previously, and previously suggested regions did not yield significant prediction in our sample. Including demographic and cognitive variables which may correlate with motor imagery neurofeedback performance and white matter structure as candidate predictors revealed an association with age but also led to loss of statistical significance and somewhat poorer prediction accuracy (69.6%). Our results suggest cast doubt on the feasibility of predicting the benefit of motor imagery neurofeedback from fractional anisotropy. At the very least, such predictions should be based on data collected using the same paradigm and with subjects whose characteristics match those of the target case as closely as possible.

P 69 Assessing the relation between brain structure and function during motor imagery in stroke patients and controls using EEG and MRI

Background Motor imagery (MI) training, in particular in combination with EEG-based neurofeedback (MI-NF), has been suggested as a potential add-on therapy for rehabilitation of upper limb motor impairments after stroke. Most MI-NF implementations are based on the event-related desynchronization (ERD) in the 8–30 Hz frequency range that is typically observed over sensorimotor areas during motor execution and imagination. The amplitude and consistency of the ERD depends, among other things, on brain structure and function during motor imagery (e.g., Halder et al., 2013 , Zich et al., 2015 ). Because the vast majority of the research on MI-NF has been conducted with young healthy individuals, it is unclear to what degree changes regarding the relationship between MI-induced ERD, MI-induced functional magnetic resonance imaging (fMRI) activation and brain structure in stroke patients are due to normal aging and the stroke, respectively. Objectives (1) to investigate in healthy older adults (>45 years) associations of MI-induced ERD, MI-induced fMRI activation and diffusion tensor imaging (DTI) measures, and (2) to investigate differences in these measures between chronic stroke patients and healthy older adults matched for age and gender. Methods We included 12 chronic stroke patients with residual upper limb motor impairment (mean age 61.5 years – range 49–75 years; 3 females) and 17 healthy older adults (mean age 60.4 years – range 48–77 years; 9 females). All participants completed a 3T MRI session and a 96-electrode EEG session. The MRI session included a high-resolution anatomical scan, DTI, and fMRI during rest, motor execution and kinesthetic MI of repeated hand opening and closing. The EEG session consisted of three blocks: motor execution, kinesthetic MI and kinesthetic MI with real-time EEG-based visual feedback, all with the same hand movement as during fMRI. Each patient also completed a motor assessment consisting of the upper limb section of the Fugl-Mayer Assessment and the Modified Ashworth Scale. Results We will present preliminary results regarding the correlations of ERD and fMRI activation related to motor execution and imagination. Moreover, we will present the results of a replication of the analysis of Halder et al. (2013) that for young healthy adults indicated a significant association between MI-induced ERD and white matter integrity (fractional anisotropy) in subcortical structures.

Farnesoid X Receptor Agonism Protects against Diabetic Tubulopathy: Potential Add-On Therapy for Diabetic Nephropathy.

Established therapies for diabetic nephropathy (dNP) delay but do not prevent its progression. The shortage of established therapies may reflect the inability to target the tubular compartment. The chemical chaperone tauroursodeoxycholic acid (TUDCA) ameliorates maladaptive endoplasmic reticulum (ER) stress signaling and experimental dNP. Additionally, TUDCA activates the farnesoid X receptor (FXR), which is highly expressed in tubular cells. We hypothesized that TUDCA ameliorates maladaptive ER signaling via FXR agonism specifically in tubular cells. Indeed, TUDCA induced expression of FXR-dependent genes (SOCS3 and DDAH1) in tubular cells but not in other renal cells. In vivo, TUDCA reduced glomerular and tubular injury in db/db and diabetic endothelial nitric oxide synthase-deficient mice. FXR inhibition with Z-guggulsterone or vivo-morpholino targeting of FXR diminished the ER-stabilizing and renoprotective effects of TUDCA. Notably, these in vivo approaches abolished tubular but not glomerular protection by TUDCA. Combined intervention with TUDCA and the angiotensin-converting enzyme inhibitor enalapril in 16-week-old db/db mice reduced albuminuria more efficiently than did either treatment alone. Although both therapies reduced glomerular damage, only TUDCA ameliorated tubular damage. Thus, interventions that specifically protect the tubular compartment in dNP, such as FXR agonism, may provide renoprotective effects on top of those achieved by inhibiting angiotensin-converting enzyme.

Long-acting muscarinic antagonists: a potential add-on therapy in the treatment of asthma?

Asthma is a chronic inflammatory disorder of the airways that is a major global burden on both individuals and healthcare systems. Despite guideline-directed treatment, a significant proportion of patients with asthma do not achieve control. This review focuses on the potential use of long-acting anticholinergics as bronchodilators in the treatment of asthma, with results published from clinical trials of glycopyrrolate, umeclidinium and tiotropium. The tiotropium clinical trial programme is the most advanced, with data available from a number of phase II and III studies of tiotropium as an add-on to inhaled corticosteroid maintenance therapy, with or without a long-acting β2-agonist, in patients across asthma severities. Recent studies using the Respimat Soft Mist inhaler have identified 5 µg once daily as the preferred dosing regimen, which has shown promising results in adults, adolescents and children with asthma. Tiotropium Respimat has recently been incorporated into the Global Initiative for Asthma 2015 treatment strategy as a recommended alternative therapy at steps 4 and 5 in adult patients with a history of exacerbations. The increasing availability of evidence from ongoing and future clinical trials will be beneficial in determining where long-acting anticholinergic agents fit in future treatment guidelines across a variety of patient populations and disease severities.

Building academic-industrial alliances to stimulate drug discovery for psychiatric diseases

Most pharmaceutical companies have ceased drug discovery programs targeting psychiatric diseases given many costly failures in the last decades. Nonetheless, there is still a strong demand in novel pharmaceutical approaches since many symptoms e. g. of schizophrenia cannot be targeted adequately. Therefore, early stage academic-industrial collaborations may offer an opportunity to address novel targets in schizophrenia and to develop and validate novel lead compounds. It has been widely accepted that Schizophrenia is likely to be a neurodevelopmental disease associated with a strong genetic component. More recently, human genetics has provided a plethora of genetic risk factors for Schizophrenia. Tailor-made transgenic animal models of individual risk factors represent promising tools to unravel the neurobiological functions of these risk factors at the developmental, cellular and systemic level. Dedicated animal models also allow for the targeted preclinical validation of novel therapeutic approaches up to behavioral consequences which are usually not accessible for the industry. In this symposium, early stage academic-industrial drug discovery approaches targeting the Neuregulin1-ERBB4 risk pathway will be presented. In a drug repurposing approach, Spironolactone was identified in a cell-based screen with clinically approved substances as a novel ERBB-inhibitor that can ameliorate behavioral deficits in mice that display increased Neuregulin1-ERBB4 signaling. These results led to the initiation of a clinical trial to assess Sprionolactone as a potential add-on therapy for schizophrenia. Moreover, academic-industrial collaborations have been fostered to develop novel lead compounds targeting Neuregulin1-ERBB4 signaling. In summary, this symposium will highlight the importance of well characterized animal models to understand the function of risk genes/pathways and their value to validate treatment options focused on neurobiological risk mechanisms of Schizophrenia.

Place of sodium-glucose co-transporter type 2 inhibitors for treatment of type 2 diabetes.

Inhibitors of sodium-glucose co-transporter type 2 (SGLT2), such as canagliflozin and dapagliflozin, are recently approved for treatment of type 2 diabetes. These agents lower blood glucose mainly by increasing urinary glucose excretion. Compared with placebo, SGLT2 inhibitors reduce hemoglobin A1c (HbA1c) levels by an average of 0.5%-0.8% when used as monotherapy or add-on therapy. Advantages of this drug class include modest weight loss of approximately 2 kg, low risk of hypoglycemia, and decrease blood pressure of approximately 4 mmHg systolic and 2 mmHg diastolic. These characteristics make these agents potential add-on therapy in patients with HbA1c levels close to 7%-8.0%, particularly if these patients are obese, hypertensive, and/or prone for hypoglycemia. Meanwhile, these drugs are limited by high frequency of genital mycotic infections. Less common adverse effects include urinary tract infections, hypotension, dizziness, and worsening renal function. SGLT2 inhibitors should be used with caution in the elderly because of increased adverse effects, and should not be used in chronic kidney disease due to decreased or lack of efficacy and nephrotoxicity. Overall, SGLT2 inhibitors are useful addition for treatment of select groups of patients with type 2 diabetes, but their efficacy and safety need to be established in long-term clinical trials.

Effect of Omalizumab as Add-On Therapy on Asthma-Related Quality of Life in Severe Allergic Asthma: A Brazilian Study (QUALITX)

Objective. To assess the impact of omalizumab as an add-on therapy to standard treatment with inhaled corticosteroids (ICS) and long-acting beta-2 agonists (LABA) on asthma-related quality of life (QoL) in patients with severe allergic asthma. Methods. This was a 20-week, randomized, open-label, study involving Brazilian patients (>12 years) with severe persistent allergic asthma inadequately controlled despite regular treatment with, at least, ICS (≥500 μg/day fluticasone or equivalent) + LABA. The primary objective was to assess the mean change from baseline in overall Asthma-related Quality of Life Questionnaire (AQLQ) score in omalizumab-treated patients compared with the control group. Secondary outcome measures included rescue medication use, incidence of asthma exacerbations, perception of treatment efficacy among patients, mean change from baseline in AQLQ score, and >1.5-point increase in overall AQLQ score. Results. In the omalizumab group, overall AQLQ score was 3.2 (0.9) (mean [SD]) at baseline and 4.4 (1.3) at week 20 versus 3.0 (1.0) at baseline and 3.0 (1.1) at week 20 in the control group. Mean change from baseline on overall AQLQ score at week 20 in the omalizumab group was 1.2 (0.2) versus 0 (0.1) in the control group, showing a significant increase in scores from baseline in the omalizumab group (p < .001). There was also a statistically significant difference (p < .001) in the number of patients who showed a >1.5-point increase from baseline in overall AQLQ score after 20 weeks, thus indicating a better QoL in the omalizumab group. There was no significant difference with respect to the use of rescue medication, incidence of asthma exacerbation, and adverse events between treatment groups. The global evaluation of treatment effectiveness was significantly better for omalizumab (p < .001). Conclusion. Omalizumab was well tolerated and significantly improved the overall AQLQ score. Hence, it is a potential add-on therapy for severe persistent allergic asthma not controlled by standard prescribed treatment in Brazilian patients.

Mozart K.448 acts as a potential add-on therapy in children with refractory epilepsy

Mozart's Sonata for two pianos in D major, K.448 (Mozart K.448), has been shown to improve mental function, leading to what is known as the Mozart effect. Our previous work revealed that epileptiform discharges in children with epilepsy decreased during and immediately after listening to Mozart K.448. In this study, we evaluated the long-term effects of Mozart K.448 on children with refractory epilepsy. Eleven children with refractory epilepsy were enrolled. All of the patients were diagnosed as having had refractory epilepsy for more than 1year (range=1year to 6years 4months, mean=3years 11months) and had been receiving at least two antiepileptic drugs (AED). During the study period, they listened to Mozart K.448 once a day before bedtime for 6months. Seizure frequencies were recorded 6months before they started listening to this music and monthly during the study period. All of the patients remained on the same AEDs during the 6-month study period. Frequencies of seizures were compared before and after listening to Mozart K.448. Eight of eleven patients were seizure free (N=2) or had very good responses (N=6) after 6months of listening to Mozart K.448. The remaining three (27.3%) showed minimal or no effect (effectiveness <50%; unmodified or worsened seizure frequency). The average seizure reduction was 53.6±62.0%. There were no significant differences in seizure reduction with IQ, etiology, or gender. We conclude that Mozart K.448 should be further studied as a potential add-on therapy in the treatment of children with refractory epilepsy.

La neuroprotection est-elle à portée de main ?

Glaucoma is no longer considered as an only IOP-dependent condition, but as a progressive neurodegenerative disease, characterized by loss of retinal ganglion cells as a result of neuronal cell injury. Several hypotheses have been raised to a better understanding of this neuronal cell death mainly driven by apoptosis. Several experimental models are under development, as well as new therapeutic approaches, aiming to slow, or stabilize glaucoma progression, as potential add-on therapy to those currently used to decrease IOP.

Probiotics in infectious diarrhoea in children: are they indicated?

Infectious gastroenteritis continues to be a leading cause of mortality and morbidity worldwide. The cornerstone of treatment remains replacement of water and electrolyte losses with oral rehydration solution. Until a few years ago, probiotics were discussed primarily in the context of alternative medicine, but they are now entering mainstream medical practice since a decrease of the severity and duration of infectious gastroenteritis in approximately 24 hours has been shown for some strains. Therefore, probiotics are a potential add-on therapy in acute gastro-enteritis. The shortening of the duration of diarrhoea and the reduction in hospital stay result in a social and economic benefit. Evidence found in viral gastroenteritis is more convincing than in bacterial or parasitic infection. Mechanisms of action are strain specific and only those commercial products for which there is evidence of clinical efficacy should be recommended. Timing of administration is also of importance. In acute gastroenteritis, there is evidence for efficacy of some strains of lactobacilli (e.g. Lactobacillus caseii GG and Lactobacillus reuteri) and for Saccharomyces boulardii. Probiotics are "generally regarded as safe", but side effects such as septicaemia and fungaemia have very rarely been reported in high-risk situations. Although most studies conclude in a statistically significant shortening of the duration of diarrhea, the clinical relevance of this finding is limited. In conclusion, selected strains of probiotics result in a statistically significant but clinically moderate benefit in shortening the duration of diarrhoea caused by acute infectious gastroenteritis.