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Objectives: To compare the 12-month retention rate, effectiveness and tolerability of perampanel (PER) as a first or late add-on treatment in adult patients with focal-onset seizures (FOS), including focal to bilateral tonic-clonic seizures (FBTCS). Methods: This retrospective, observational, multicenter study was carried out in patients with FOS that received PER as a late add-on (n = 60), after failure of > 3 AEDs, and a group that received PER as a first add-on treatment (n = 21). Results: At 12 months, the retention (90.5 % vs. 48.3 %; p = 0.001), seizure-freedom (71.4 % vs. 13.3 %; p < 0.001) and responder (85.7 % vs. 28.3 %; p < 0.001) rates were significantly higher in the first add-on group compared with the late add-on group. In patients with FBTCS, the 12-month retention rate did not differ significantly between the first and late add-on groups (93.8 % vs. 66.7 %); however, seizure-freedom (81.2 % vs. 27.8 %; p = 0.002) and responder rate response (93.8 % vs. 44.4 %; p = 0.002) were significantly higher in the first add-on group. There were no significant differences in tolerability between the two groups, including in patients with FBTCS. Adverse events were reported in 54.3 % of patients (44/81), most were mild or moderate, with dizziness being the most frequent one. Conclusion: Overall, retention rate and effectiveness at 12 months were significantly higher in patients taking PER as a first add-on than as a late add-on, and the tolerability of PER did not differ significantly between groups. PER demonstrated high effectiveness in patients with FBTCS, even as a late add-on treatment.

Background & Objective:Migraine is an occasional headache that represents neurological and gastrointestinal symptoms, as well as changes in the autonomic nervous system. Biofeedback is a non-pharmacological technique used to treat migraine headaches and is proven to reduce headaches and improve performance. The present study aimed to compare the efficacy of biofeedback and pharmacological treatments to find the best treatment strategy for migraine headaches. Materials & Methods:This randomized clinical trial was performed on 86 patients who referred to Noor Psychiatric Clinic and Neurology ClinicofValiasr Hospital, Zanjan, Iran. Patients were divided into two groups of daily treatment with medication and treatment with medicine and biofeedback. Cases were monitored every two months using interviews and questionnaires. Results:The study was carried out on 86 migraine patients with the age range of 31-45 years for 3 months. Most of the patients were female, including 90.7% of the individuals in the case group and 81.4% of the control group. The frequency distribution of medication use was not different between the two groups (P=0.744). Most of the participants had a history of more than 1 year of headache. During the treatment, the frequency and severity of attacks reduced obviously until the 8thweek. The decrease in the Migraine Disability Assessment (MIDAS) score was more significant in the biofeedback group, except in the 10thand 12thweeks. However, the decline in the MIDAS score was not significant. Moreover, the reduction in the frequency of attacks remained significant until the end of the study. Conclusion:It can be concluded that the combination of biofeedback treatment and medication therapy provides a more rapid response than pharmacological treatment alone. Therefore, biofeedback is an effective add-on therapy, which can be taken into consideration for diminishing all aspects of migraine headache attacks.

Asthma is a heterogeneous disease characterized by airway inflammation resulting from complex interactions between multiple hosts as well as environmental factors. As a chronic respiratory condition, asthma exerts a significant impact on patients and the healthcare system. Per the Global Initiative for Asthma (GINA), inhaled corticosteroids (ICS) with/without long-acting beta

The refractory epilepsy adds to the global burden of epilepsy as about 25 % of all patients with epilepsy present drug-resistant epilepsy. The P-glycoprotein (P-gp) plays a vital role in the mechanism of resistance in epilepsy. The AED levels in the brain are regulated by the P-gp transport. The upregulation of P-gp results in low concentration of AEDs inside the brain parenchyma and thus leads to resistance. There are three main conditions which lead to decrease transport of AEDs in refractory epilepsy. First being AEDs as substrate of P-gp; secondly, the elevated expression of P-gp in patients with drug resistant epilepsy as compared to drug-responsive patients; thirdly, the low brain AED concentration in refractory epilepsy in comparison to drug-responsive epilepsy. Therefore, determination of P-gp substrate should be a criterion for the selection of new AED for management of refractory epilepsy. This review highlights various tools which help in identification of P-gp substrates and also illustrates a concept of using various novel non-P-gp substrates which can cross the blood brain barrier and leads to enhanced accumulation inside the brain. Hence, these non P-gp substrates can be used as an add on treatment for the management of resistant epilepsy.

Yeni, S. Naz/0000-0001-7372-5430 WOS:000521935300002 Objective: Patients with drug-resistant focal or generalized epilepsy are important in terms of treatment and polytherapy necessity, adverse effect profiles of drugs, and seizure control difficulties. Clobazam (CLB), which has a lesser sedative effect than other benzodiazepines, is frequently used in different countries. In this study, we aimed to present the results related to the demographic characteristics, adverse effects, and treatment efficacy of patients under CLB treatment. Materials and Methods: Patients who were followed up in the outpatient clinic of Cerrahpasa Medical Faculty were screened retrospectively. Sex, age of seizure onset, duration of epilepsy, seizure type, duration of drug use, frequency of seizures before and after CLB, and drug adverse effects were investigated. The decrease in seizure frequency could not be quantitatively evaluated in some patients because the study was retrospective. For this reason, two groups were identified as having a significant reduction in seizure frequency and being seizure-free according to the information provided by the parents and the recorded data. Results: Forty-one patients with CLB who were followed in the epilepsy clinic were examined. The mean age of 26 male and 15 female patients was 30.30 years. The mean duration of epilepsy was 20.4 years. It was determined that 16 patients were either seizure-free or had intervening rare, mild seizures. There was a significant decrease in seizure frequency in nine patients. Headache was observed in one patient, and sedation and dizziness in two patients. Conclusion: CLB is especially recommended for add-on therapy in Lennox-Gastaut syndrome. In this study, it was observed that in focal/generalized, idiopathic/ cryptogenic different groups, 39% of the patients were seizure-free. However, this effect was not lost during the mean follow-up period of 12.2 months. Although the value of this data decreases due to its retrospective nature, the place of CLB in the treatment of focal/generalized epilepsy is important.

Background: Montelukast, as a non-steroidal anti-inflammatory drug, could reduce inflammation in nephrotic syndrome (NS). This study aimed to evaluate the therapeutic effect of montelukast as adjunctive agent in pediatric NS. Methods: This clinical trial study was conducted on patients with NS. The patients were assigned into two equal groups (N = 25 in each) of intervention (steroid + montelukast) and control and treated for one month. One month later, in the follow-up stage, their proteinuria was measured. The results before and after treatment were statistically analyzed by SPSS software version 21, and the final report of the project was presented. Results: The age of participants in the intervention and control groups was 7.26 ± 4.23 and 6.79 ± 3.91 years, respectively (P = 0.68), and there were 10 female participants in both groups (P = 1.0). Albumin levels in 96% of the control group and 76% of the intervention group were 1.5 - 2.5 μg/dL (P = 0.037). Also, 48% of participants in the control group were corticosteroid dependent, and 60% of participants in the intervention group responded to corticosteroids (P = 0.194). The severity of nephrotic syndrome was moderate in 60% of participants in the control group and mild in 60% of participants in the intervention group (P = 0.138). Conclusions: The results of present study showed that recovery rate was higher in the intervention group, but the difference was not statistically significant.

INTRODUCTION AND OBJECTIVE:The aim of this study was to identify the clinical factors resulting in the failure of dutasteride add-on treatment to alpha-adrenergic antagonist in patients with LUTS a...

Background: We aimed to critically evaluate the effectiveness and safety of acupuncture as an add-on therapy to conventional Western medication (WM) and assess the quality of evidence (QoE) of these findings.Methods: A total of 12 English, Korean, and Chinese databases were searched on December 18, 2020. Randomized controlled trials (RCTs) assessing the effectiveness of acupuncture as an add-on therapy to conventional WM for functional dyspepsia (FD) were included. The primary outcome was the symptom score of FD. The risk of bias of the included studies and QoE were evaluated using the Cochrane Collaboration's risk of bias tool and Grading of Recommendations, Assessment, Development, and Evaluation method, respectively.Results: A total of 22 RCTs were included. The total and individual FD symptom scores were significantly improved in the acupuncture combined with WM groups compared with the WM alone groups, except for in one study. The Nepean dyspepsia index score and total effective rate mostly improved significantly in the acupuncture group, regardless of the WM used and acupuncture type. FD-related biomarkers, such as ghrelin and gastrin levels, showed mixed results. The acupuncture group showed a significantly lower recurrence rate after 3–6 months of follow-up than the WM alone group. There were no differences in the incidence of adverse events between the two groups. The included studies generally had low methodological quality. The QoE for the main findings was generally very low to moderate.Conclusion: Limited evidence suggests that acupuncture has the potential to improve FD treatment in combination with conventional WM. Furthermore, the methodological quality of the included studies and QoE of the main findings were generally low. Therefore, RCTs with a rigorous methodology, including sham acupuncture and multiethnic subjects, should be performed.Systematic Review Registration: OSF registries [https://osf.io/mxren], PROSPERO [CRD42021226608].

BackgroundPreclinical and clinical studies indicate a role for MLC901 (NeuroAiDTMII) in Alzheimer’s Disease (AD). We investigated its safety and efficacy as add-on therapy to standard treatment and evaluated a disease modifying effect in mild to moderate AD.MethodsMild-moderate probable AD patients by NINCDS-ADRDA criteria, stable on acetylcholinesterase inhibitors or memantine (n=125) were randomized to receive MLC901 (early starters) or placebo (delayed starters) for 6 months, followed by a further 6 months during which all patients received MLC901, in a delayed-start design. The primary outcome measure was serious adverse events at 6 months, secondary outcomes included the Alzheimer's Disease Assessment Scale - Cognitive subscale (ADAS-Cog) and other cognitive assessment scales.ResultsThere was no significant difference in the risk of serious adverse events between early and delayed starters at month (M) 6 (22.6% vs. 27.0%, risk difference = -4.4%, 90% CI -16.9 to 8.3%). Furthermore, there was no significant difference in the risk of adverse events, including the occurrence of stroke or vascular events, between early and delayed starters throughout the 12-month study period. The early-starters differed significantly on ADAS-Cog from the delayed-starters at M9 (mean difference -3.36, 95% CI -5.64 to -1.09) and M12 (mean difference -2.35, 95% CI -5.45 to 0.74). Other cognitive assessment scales showed trends in favor of MLC901.Conclusions MLC901 is a safe adjunct to standard treatment for mild-moderate AD. There is no indication that the risk of any adverse events, including vascular, is increased with MLC901 in the study population. The cognitive outcomes provide support for a disease-modifying effect of MLC901 which requires confirmation in further studies. Clinical trial registration: ClinicalTrials.gov, NCT03038035. https://clinicaltrials.gov/ct2/show/NCT03038035

Background: N-methyl-glycine (sarcosine) may improve symptoms of schizophrenia via NMDA-receptor modulation. We undertook a systematic review and meta-analysis to determine the short- and long-term effectiveness of sarcosine for schizophrenia. Research design and methods: The databases Medline, Scopus, EMBASE, Cochrane Library, and PsycINFO were searched. We included six independent randomized controlled trials of sarcosine as add-on treatment to current antipsychotic medication, involving 234 adult participants with schizophrenia, and reporting data on symptom severity. Standardized mean differences (SMDs) were used to assess continuous outcomes. Results: In all of the trials, sarcosine was administered orally at 2 g/day. Treatment with sarcosine did not show a significant effect size at any of the pre-established time points (2, 4, 6, or >6 weeks), due to marked quantitative heterogeneity. However, sarcosine was associated with significant reductions of symptom severity in the subgroups of people with chronic schizophrenia and no treatment resistance (namely, without added-on clozapine) in relation to the SMD after 6 weeks treatment at −0.36 and −0.31, respectively. Conclusions: People with chronic and non-refractory schizophrenia may benefit from the use of sarcosine as an add-on treatment to antipsychotic medication. Due to the good tolerability of this compound, future trials with larger sample sizes appear worthwhile.

Stefan Zielen,1 Gianna Reichert,1 Helena Donath,1 Jordis Trischler,1 Johannes Schulze,1 Olaf Eickmeier,1 Martin Eckrich,2 Katharina Blumchen1 1Department for Children and Adolescents, Division of Allergology, Pulmonology and Cystic Fibrosis, University Hospital Frankfurt, Frankfurt, Germany; 2Group Practice Dres. Med. Martin Eckrich and Matthias Gründler, Offenbach am Main, GermanyCorrespondence: Stefan ZielenDepartment for Children and Adolescents, Division of Allergology, Pulmonology and Cystic Fibrosis, University Hospital Frankfurt, Theodor-Stern-Kai 7, Frankfurt 60590, GermanyTel +49 (69) 6301-83063Email Stefan.Zielen@kgu.deBackground: Toddlers with asthma suffer disproportionally more than school-aged children from exacerbations with emergency visits and hospital admissions despite inhaled corticosteroid (ICS) treatment. A recent trial for children ≤ 5 years showed tolerability of tiotropium and potential to reduce asthma-related events.Methods: We conducted a retrospective analysis of electronic outpatient records (2017‒2019) of children < 6 years treated with ICS plus long-acting β2-agonists (LABAs) plus tiotropium as an add-on for uncontrolled severe asthma. The primary endpoint was a comparison of systemic corticosteroid (SCS) prescriptions 6 months before and after ICS/LABA/tiotropium start. Secondary endpoints included physician visits, hospitalisations and antibiotic prescriptions. We compared outcomes with children without asthma matched for age, sex, season and screening date.Results: Compared with a mean 2.42 (95% CI: 1.75, 3.36) SCS courses per patient within 6 months prior to ICS/LABA/tiotropium, 0.74 (95% CI: 0.25, 1.08) SCS courses per patient were prescribed within 6 months after starting ICS/LABA/tiotropium (P< 0.001). Physician visits dropped from 9.23 (95% CI: 7.15, 12.72) to 5.76 (95% CI: 3.10, 7.70) per patient (P< 0.01). Nineteen hospitalisations were recorded 6 months before ICS/LABA/tiotropium compared with one hospitalisation after (P< 0.01). A mean 1.79 antibiotic courses (95% CI: 1.22, 2.23) per patient were prescribed before ICS/LABA/tiotropium compared with 0.74 (95% CI: 0.22, 1.00) after ICS/LABA/tiotropium (P< 0.001). Hospitalisation rates for patients at observation end were not statistically different from healthy controls before/after matching.Interpretation: Our retrospective study showed that adding tiotropium to ICS/LABA is a new treatment option for patients with severe preschool asthma; however, larger confirmatory studies are needed.Keywords: preschool asthma, severe uncontrolled asthma, tiotropium, inhaled steroids, long-acting β2-agonists, LABAs

Background:Cognitive behavioural therapy (CBT) is currently the treatment of choice for most anxiety disorders. Yet, with recovery rates of approximately 50%, many patients fail to achieve complete remission. This has led to increased efforts to enhance treatment efficacy. Physical exercise (PE) has in recent years been advocated as means to augment the effects of CBT for anxiety disorders. PE appears to reduce anxiety through other mechanisms than CBT, some of which might also have the potential to augment the effects of psychological treatment.Aims:The current review aimed to summarize and discuss the current research status on CBT augmented with PE for anxiety.Method:A systematic literature search was conducted in the databases PsychInfo, Medline and Web of Science to evaluate the potential augmentative effect of combining PE with CBT for anxiety disorders. These effects were intended to be evaluated in a meta-analysis, but findings from the few and diverse studies were better summarized in a systematic review.Results:Eight articles were included in this review, of which two had no control group, while six had from two to four experimental arms. Six of the studies concluded in favour of benefits of add-on PE, while two studies found no added benefits of the combined interventions.Conclusions:The combination of PE and CBT appears feasible. Add-on PE seems to be more beneficial for clinical populations, when administered regularly several times per week, across several weeks. Future studies should investigate further how and for whom to best combine PE and CBT.

The proliferation and popularity of additional treatments in IVF, also known as add-ons, has generated widespread discussion and controversy in the UK, where concerns have addressed the lack of evidence to support the efficacy and safety of these treatments, their cost, and their connection to a wider context of privatisation of fertility treatment. Drawing on 42 interviews with IVF patients, this article explores the role of hope in the appeal of add-ons from the patient perspective. The analysis is presented in two parts: firstly, we investigate the role of hope in patients’ decision-making on treatment, contextualising add-ons in the broader trajectory of their IVF experience; secondly, we examine how patients navigate the offer of add-ons, focusing on the role of hope in how they rationalise their decisions on whether to include them in their fertility treatment. Our analysis shows how patients craft their hope to navigate the increasing number of available options in their quest to find the treatment(s) that will “work” for them. We suggest that the imperative for patients to explore all options is intensified with the emergence of add-ons, which produces a novel context and version of a “hope technology”., Highlights • The role of hope in the appeal of IVF add-ons. • Patient perspectives on the inclusion of add-ons in fertility treatments. • Contextualisation of add-ons in patients' IVF trajectory. • In-depth analysis of how IVF hope narratives shape treatment decisions of IVF patients. • How patients craft hope in relation to add-ons.

Background Perampanel (PER) is an effective adjunctive therapy for controlling focal-onset seizures (FOS), but few studies have examined its effects as an early add-on for the treatment of FOS in daily clinical practice. Methods Our retrospective, multicenter, observational study evaluated the effectiveness and safety of PER as an early add-on in 77 patients with FOS, with and without focal to bilateral tonic-clonic seizures (FBTCS) after 3, 6 and 12 months in a real-world setting. Results After 12 months of treatment (median dose 6 [4,8] mg/day), the retention rate was 79.2 % and 60 % of patients (39/65) experienced a ≥50 % reduction in seizure frequency relative to baseline. The seizure-free rate was 38.5 % for all seizures (25/65) and 60 % for FBTCS (12/20). The responder rate at 12 months was significantly higher when PER was given with one concomitant AED (72.2 %) compared to when PER was given with two concomitant AEDs (44.8 %). Drug-related adverse events (AEs) were reported in 40.3 % of patients, most of them being mild (64.2 %). Twelve patients (15.6 %) discontinued treatment because of AEs. Conclusions PER is an effective and safe early add-on for patients with refractory FOS, especially for those with FBTCS.

Background:In recent years, many studies reported the anti-Hp effects of Traditional Chinese Medicine. Based on these studies, there had been many relevant systemic reviews and meta analyses with variable results Aim: This overview aims to investigate the general characteristics and assess the methodological quality of these systemic reviews/meta ana lyses (SR/MAs). Method: In this overview, we intend to includ systemic reviews/meta analyses with comparison of Chinese medicine and western medicine on helicobacter pylori infection by searching databases of Medline, Embase, Web of Science, China National Knowledge Infrastructure Database (CNKI), Chinese VIP Information (VIP), Chinese Medical Databases (CMB) and Wan-Fang Database until December 16th, 2018. AMSTAR and GRADE tools will be adopted to assess the methodological quality and evidence quality characteristics. Conclusion:The methodological quality of these SR/MAs will be assessed as clinical evidence and our result may help further use of them.

The treatment of Alzheimer's disease (AD) in the field of non-pharmacological interventions is a challenging issue, given the limited benefits of the available drugs. Cognitive training (CT) represents a commonly recommended strategy in AD. Recently, repetitive transcranial magnetic stimulation (rTMS) has gained increasing attention as a promising therapeutic tool for the treatment of AD, given its ability of enhancing neuroplasticity. In the present randomized, double-blind, sham-controlled study, we aimed at investigating the add-on effect of a high frequency rTMS protocol applied over the left dorsolateral prefrontal cortex (DLPFC) combined with a face-name associative memory CT in the continuum of AD pathology. Fifty patients from a very early to a moderate phase of dementia were randomly assigned to one of two groups: CT plus real rTMS or CT plus placebo rTMS. The results showed that the improvement in the trained associative memory induced with rTMS was superior to that obtained with CT alone. Interestingly, the extent of the additional improvement was affected by disease severity and levels of education, with less impaired and more educated patients showing a greater benefit. When testing for generalization to non-trained cognitive functions, results indicated that patients in CT-real group showed also a greater improvement in visuospatial reasoning than those in the CT-sham group. Interestingly, this improvement persisted over 12 weeks after treatment beginning. The present study provides important hints on the promising therapeutic use of rTMS in AD.

Objectives: Lacosamide is a third-generation antiepileptic agent that selectively enhances slow inactivation of sodium channels that takepart in generation and propagation of action potentials and results in the diminution of neuronal excitability. Because of this new mechanismof action, it is expected to be efficacious in patients with drug-resistant epilepsy. In this study, we aimed to assess the efficacy andtolerability of lacosamide add-on treatment in refractory epilepsy patients by presenting our experience in a tertiary referral center.Methods: Medical records of refractory focal epilepsy patients who were followed in epilepsy outpatient clinic between October 2014 andMay 2017 were retrospectively reviewed in this study. Patients who were treated with add-on lacosamide and completed minimum of sixmonths follow-up period were included. ≥50% reduction in seizure frequency was defined as treatment response.Results: In this study, 88 patients were included. The percentage of seizure-free patients after six months follow-up was 4.6% and the treatmentresponse rate was 55.6%. We also evaluated the effect of concomitant use of sodium channel blockers, the presence of abnormalfindings on magnetic resonance imaging and the introduction stage of lacosamide. No significant difference was observed in the responserate regarding the mentioned parameters. 19% of the patients reported side effects, the majority of which were dizziness, vertigo and somnolence.None of them discontinued treatment because of side effects.Conclusion: Our findings suggest that lacosamide add-on therapy is effective in refractory focal epilepsy and has an appropriate tolerabilityand safety profile since none of the patients stopped treatment due to side effects.Keywords: Refractory epilepsy; lacosamide; responder rate.

There are now multiple monoclonal antibodies targeting different inflammatory pathways of severe asthma. Benralizumab is a recently approved monoclonal antibody indicated for the treatment of severe eosinophilic asthma by targeting a subunit of the IL-5 receptor. Treatment with benralizumab results in significant reductions of blood and tissue eosinophils. Early studies report that this therapy has an adequate safety profile, and this was confirmed in later trials. Phase III studies have shown that benralizumab is effective in reducing the rate of exacerbations and improving asthma symptoms and quality of life in patients with severe eosinophilic asthma. Additionally, treatment with benralizumab has resulted in important reductions in the use of chronic oral corticosteroids. In this review, we evaluate the evidence up to date on the efficacy of benralizumab in severe eosinophilic asthma and explore the implications of this therapy in the ever-growing landscape of therapies for severe asthma.

Objective To evaluate the improvement of survival rate for patients after cardiopulmonary resuscitation (CPR) by Shenfu Injection. Method Electronic databases including Medline, Embase, Web of Science, Cochrane Central Register of Controlled Trial, Wanfang Database, and VIP Database were searched with the search terms of "Shenfu Injection”, “cardiopulmonary resuscitation”, “randomized controlled trials” and their synonyms. A funnel plot was adopted to evaluate publication bias. The meta-analysis was performed using a fixed effects model in case of low heterogeneity and a randomized effects model in case of high heterogeneity. Conclusion Add on treatment of Shenfu Injection may improve the survival rate of the patients after CPR.

Attachment Based Short Intervention During Inpatient Treatment of Adolescents In clinical attachment research the established and economic Adult Attachment Projective Picture System (AAP) has been increasingly used in the past few years to assess the attachment representations in adults and recent studies demonstrated sufficient validity for assessing attachment representations in adolescents. Apart from coding attachment classifications, the AAP provides useful and clinically valid information concerning attachment related defences, aspects of capacity to act and synchrony in relationships and emotion regulation strategies with respect to attachment related traumatic experiences. These valuable aspects with respect to individual resources led to the conceptualization to implement the AAP in the therapeutic setting as a feedback tool. In this pilot case we report on an adolescent patient in an inpatient setting. The therapist received an individualized feedback on the patients' AAP to focus on specific attachment related themes used as a short intervention respective an add-on treatment. This paper presents the first results of this new approach by demonstrating the potential therapeutic effects and process of therapy.

Bipolar affective disorder (BPAD) is a chronic debilitating psychiatric illness seriously affecting the quality of patients’ life. The available treatment is effective in about half of those suffering from the illness. The neurobiological basis of the disorder is not fully unraveled. With such lacunae, attempts have been made to decipher the underlying neuroimmunological process of the illness as is the case with other mental disorders. As a result, some inflammatory processes have been implicated in the etiology of BPAD, as described in this communication. Subsequently, the role of anti-inflammatory agents such as celecoxib was investigated by treating different phases of BPAD. Given the promising outcomes of several trials and reviews, celecoxib has gained momentum and has been recommended as an adjunctive treatment by some guidelines for treating resistant BPAD cases. This brief communication highlights some of the caveats in the randomized trials using celecoxib as an add-on treatment in bipolar mania specifically, which need to be addressed in future work.

Contains fulltext : 191992.pdf (Publisher’s version ) (Closed access) Background: Only 60% of depressed patients respond sufficiently to treatment, so there is a dire need for novel approaches to improve treatment effects. Cognitive Bias Modification (CBM) may be an effective and easily implemented computerized add-on to treatment-as-usual. Therefore, we investigated the effects of a positivity-attention training and a positivity-approach training compared to control trainings. Methods: In a blinded randomized-controlled design, 139 depressed inpatients received either the CBM Attention Dot-Probe Training (DPT) or the CBM Approach-Avoidance Training (AAT), next to treatment as usual. N = 121 finished all four training sessions. Both trainings had an active and a control condition. In both active conditions, patients were trained to preferentially process generally positive pictures over neutral pictures. Depressive symptom severity was assessed before and after CBM, and positivity bias was measured at the start and end of each session. Results: Clinician-rated depressive symptom severity decreased more in patients who received the active condition of the DPT or the AAT compared to patients in the control conditions. Significant change in positivity bias was found for the DPT (not the AAT), but did not mediate the effect of the training on depressive symptoms. Conclusions: The results suggest that both types of CBM (i.e., DPT and AAT) may provide a fitting add-on treatment option for clinical depression. The working mechanisms and optimal dose of CBM trainings, plus their possible combination, should be examined in more detail. 9 p.

In literature there is a growing evidence that in cervical dystonia (CD) rehabilitation, both in person and remotely, is an efficacious add on treatment to botulinum neurotoxins (BoNT) injections, but there is no consensus about protocols. We present here two rehabilitation programs implemented by our neuro‐rehabilitative multidisciplinary team. The enclosed video clips show exercises to be performed at home as self‐rehabilitation program, and exercises presented by a physiotherapist for a telerehabilitation program. These two protocols may be helpful for integrating rehabilitation with BoNT treatment in CD.

Background Fremanezumab (formerly TEV-48125) is a monoclonal antibody directed against calcitonin-gene-related peptide (CGRP), a validated target for migraine preventive therapy. In two previous phase 2 studies, fremanezumab administered once every 28 days for 12 weeks was found to be effective and safe as a preventive treatment for patients suffering from episodic migraine (EM) and chronic migraine (CM). Objective To evaluate the efficacy and safety of fremanezumab as an add-on preventive therapy in individuals with EM and CM who are on stable doses of preventive migraine medications. Methods Two randomized placebo-controlled studies tested once-monthly subcutaneous injections of various dosing regimens of fremanezumab versus placebo in EM and CM. Headache information was captured daily using an electronic headache diary. For these post hoc analyses, data were pooled from patients who were on stable preventive medications and taking fremanezumab doses of 225 mg or 675/225 mg, or placebo. Results The sample consisted of 133 patients, (67 fremanezumab and 66 placebo). Total reduction in migraine days for the duration of the study was 12.4 for fremanezumab and 7.4 for placebo (P = .0321). There were also decreases in moderate/severe headache days (12.5 vs 7.1, P = .0058), and days using acute medication for headaches relative to placebo (11.6 vs 7.5, P = .0414). Treatment emergent adverse events were generally mild and transient, and no serious adverse events were considered to be treatment-related by the site investigators. Conclusions The findings from these post hoc analyses suggest that fremanezumab is a safe and effective add-on treatment for migraine patients being concomitantly treated with other migraine preventive medications. Trials are registered at Clinicaltrials.gov NCT02025556 and NCT02021773.

Add-on treatments in IVF are utilized to a great extent but without sufficient evidence showing their effectiveness. Since the offered treatments are usually costly and may be associated with yet unknown risks, this practice is not in the best interest of couples that may go to great lengths to conceive and have an offspring carrying their own genetic make-up. A recent addition to this armamentarium is the administration of platelet-rich plasma (PRP) in women with diminished ovarian reserve, implantation failures, and a thin endometrium. The only evidence for PRP comes from small scale and mostly before and after studies with clinically irrelevant end points. PRP has not been subjected to a rigorous clinical trial. It is a typical example of an add-on gaining widespread popularity based on biological plausibility and mind-bending theoretical presumptions. We should be extremely cautious prior to implementing PRP on a widescale and await the results of well-designed studies.

Objective High Amplitude Low Frequency–Music Impulse Stimulation (HALF‐MIS) is a form of Vagus Nerve Stimulation (VNS). The aim of the study was to determine the feasibility, efficacy, and potential side effects of HALF‐MIS, used as an add‐on treatment for depression. Methods This is an open randomized controlled pilot study. Patients with depressive disorder were randomly allocated to either a HALF‐MIS group with eight add‐on HALF‐MIS sessions (over a period of 3–4 weeks) or a control group which received treatment as usual. Seated in a specially designed chair() embedded with a transducer, their central nervous system was stimulated through the abdomen, () using music and vibration. Hamilton rating was performed. Side effects were registered. Results Eighteen patients were randomized to the add‐on treatment and 20 patients to the control group. Both groups show in Hamilton Depression Rating Scale (HDRS)‐17 and in HDRS‐6, although the HALF‐MIS group had a greater decline of symptoms. This was a significant difference in intergroup analysis (p = .011, CI 95% for the HALF‐MIS group 3.0588–8.5327 and CI 95% for the control group 0.2384–3.0). The (HDRS)‐6 difference was also significant (p = .020, CI 95% for the HALF‐MIS group 1.5911–5.0487 and for the control group −0.297 to 1.7058). No side effects were observed. Conclusions High Amplitude Low Frequency–Music Impulse Stimulation treatment seems to give beneficial effect as an add‐on treatment for depression. HALF‐MIS appears to be a safe and effective add‐on treatment for depression., Music Impulse Stimulation (High Amplitude‐Low Frequency) is applied as an add‐on treatment for depression and shows promising results.

Pulmonary arterial hypertension (PAH) therapy has revolutionised the therapy of patients with Eisenmenger syndrome. Footnotes This manuscript has recently been accepted for publication in the European Respiratory Journal . It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article. Conflict of interest: Dr. D'Alto reports grants and personal fees from Actelion, grants and personal fees from Pfizer, grants and personal fees from GlaxoSmithKline, grants and personal fees from Dompe, grants and personal fees from Bayer/MSD, outside the submitted work. Conflict of interest: Dr. Constantine reports grants from Actelion, outside the submitted work. Conflict of interest: Dr. Balint reports personal fees from Actelion, personal fees from Lilly, personal fees from AOP Orphan, personal fees from Bayer/MSD, outside the submitted work. Conflict of interest: Dr. Romeo reports grants and personal fees from GlaxoSmithKline, grants and personal fees from Dompe, grants and personal fees from MSD, outside the submitted work. Conflict of interest: Dr. Argiento reports grants and personal fees from GlaxoSmithKline, grants and personal fees from Dompe, grants and personal fees from MSD, outside the submitted work. Conflict of interest: Dr. Ablonczy has nothing to disclose. Conflict of interest: Dr. Skoro-Sajer reports grants and personal fees from AOPOrphan Pharmaceuticals, grants and personal fees from Actelion, grants and personal fees from Bayer, grants and personal fees from GlaxoSmithKline, grants and personal fees from Pfizer, grants and personal fees from United Therapeutics, outside the submitted work. Conflict of interest: Dr. Giannakoulas reports grants and personal fees from Actelion, grants and personal fees from United Therapeutics, grants and personal fees from Pfizer, grants and personal fees from GlaxoSmithKline, grants and personal fees from Bayer/MSD, grants and personal fees from Pfizer, grants and personal fees from Lilly, outside the submitted work. Conflict of interest: Dr. Dimopoulos reports grants, personal fees and non-financial support from Actelion, personal fees from Pfizer, personal fees from GlaxoSmithKline, personal fees from Bayer/MSD, outside the submitted work.

Objective:The objective of this study was to investigate the effectiveness and safety of interferon (IFN) α2a as an add-on treatment for refractory Behçet’s uveitis (BU).Methods:In this retrospective cohort study, 30 refractory BU patients who received IFNα2a treatment in Peking Union Medical College Hospital between February 2015 and June 2018 were consecutively included. IFNα2a was used mainly as an add-on treatment for BU patients who underwent relapse under corticosteroids and conventional immunosuppressive agents. The primary outcome was treatment success rate before and after initiation of IFNα2a. Changes in ocular relapse rates, disease activity, corticosteroid- and immunosuppressant-sparing effects, as well as side effects were secondary outcomes.Results:A total of 30 patients (27 males and 3 females) with a mean age of 30.5 ± 8.7 years were included. Twenty-one patients (70%) were treated with at least 2 immunosuppressive agents before the initiation of IFNα2a. Treatment success was achieved in 26 patients (86.7%), and the median uveitis relapse rate decreased from 7.3 (range 2–12) to 0 (range 0–6) per patient-year ( p = 0.000002) during a mean follow-up of 21.7 ± 7.5 months, corticosteroids were lowered in 25 cases (83.3%) and completely withdrawn in four (13.3%). In addition, immunosuppressive agents were reduced in number and dosage in 22 (73.3%) and 29 patients (96.7%), respectively, and were completely withdrawn in 12 cases (40%). No severe adverse events were observed and serum autoantibodies remained negative during the treatment of IFNα2a.Conclusion:IFNα2a is effective and relatively safe in refractory BU, with significant steroid- and immunosuppressant-sparing effects.

Introduction: 1 in 11 adults have DM globally,1 and Hispanics have higher complication rates.2 A study determined that ~$16,750/year are spent by patients in medical related costs, of which ~$9,600 are related to diabetes.3 Half of Type 2 Diabetes Mellitus (T2DM) patients aren't achieving HbA1C targets,4 uncovering the need for treatment intensification. The primary purpose of this study was to assess the mean reduction in HbA1C between T2DM patients treated with SGLT2 inhibitors (SGLT2I) as adjunct therapy versus patients using other treatments not including SGLT2I. METHOD: T2DM patients with HbA1C > 7 (n=130) were selected for this retrospective cohort study; 69 SGLT2I users and 61 SGLT2I non-users. Medical records were reviewed and demographics, treatment received, HbA1C and side effects were evaluated during a 6-month follow-up period. RESULTS: The average baseline HbA1C for patients using vs not using SGLT2I as add-on was similar with a mean difference of 0.225 [CI -0.41-0.86], p

BACKGROUND AND PURPOSE The pathophysiological model of tics generally describes disruption of γ-aminobutyric acid transmission, and taurine is found to be an agonist of γ-aminobutyric acid receptors. The study aimed to evaluate the safety and efficacy of taurine as an add-on treatment for tics. METHODS Four hundred and four youngsters with tic disorders were randomly assigned to 12 weeks of either oral taurine or placebo. The Yale Global Tic Severity Scale was used to measure tic severity. The primary outcome measure was global severity scores reduced by more than 60% compared with baseline scores. RESULTS Three hundred and eighty-two patients were successfully treated. At week 4, no significant differences were found in the treatment effect and the total occurrence of adverse drug reactions between the taurine and placebo groups. At week 12, the proportion of significant improvement in tics was significantly higher in the taurine group than the placebo group (53.4% with taurine versus 34.5% without taurine; relative risk 1.546; P

To evaluate the efficiency of plasma exchange (PE) add-on on optic neuritis (ON) in neuromyelitis optica spectrum disorders (NMOSD). Our ambispective, nonrandomized study was performed in Southwest Hospital, Southwest Eye Hospital, Army Medical University. We studied 31 consecutive NMOSD patients characterized by ON and hospitalized from September 2015 to May 2018. Their clinical features were assessed, and efficiency of PE add-on treatment in ON of NMOSD was evaluated. Correlation was assessed between the effect of steroid pulse therapy (SPT) and the number of ON episodes in NMOSD. All 31 NMOSD patients accepted SPT; 15 patients of them accepted SPT and PE add-on. In these 15 patients, after PE add-on treatment, the patients’ visual acuity was further significantly improved (P = 0.000, N = 23), including 3 no light perception (NLP) patients. After the treatment, the visual function recovered quickly in the first 2 months and then gradually slowed down; the visual function remained stable about 6 months later. The correlation coefficient between visual acuity improvement of SPT and the number of ON episodes was − 0.311 (P = 0.030, N = 49). One clinical feature of NMOSD can be repeated vision impairment. In NMOSD patients characterized by ON, efficacy of SPT is limited as the number of episodes increased, and PE add-on is more effective. Even though the visual acuity of NMOSD patients decreases to NLP during episodes, there is still a chance to restore vision by PE add-on treatment.

Major Depression Disorder (MDD) is accompanied by an immune response characterized by increased levels of pro-inflammatory and immune-regulatory cytokines and cytokine-induced stimulation of indoleamine-2,3-dioxygenase (IDO). There is also some evidence that anti-inflammatory drugs may have a clinical efficacy in MDD.The aim of this study is to examine the clinical effects of an eight-week combinatorial treatment of ketoprofen (a nonsteroidal anti-inflammatory drug) combined or not with sertraline, on serum levels of IDO, interferon (IFN)-γ, interleukin (IL)-4 and transforming growth factor (TGF)-β1 in association with changes in the Beck-Depression Inventory-II (BDI-II). The study included 140 MDD patients and 40 normal controls. The pre-treatment serum levels of IDO, IFN-γ, TGF-β1 and IL-4 were significantly higher in MDD patients compared with the control group. Treatment with sertraline with or without ketoprofen significantly reduced the increased baseline production of all 4 biomarkers to levels which were similar as those of normal controls. Ketoprofen add-on had a significantly greater effect on IDO and BDI-II as compared with placebo. The reductions in IDO, IL-4 and TGF-β1 during treatment were significantly associated with those in the BDI-II.In conclusion, the clinical efficacy of both sertraline + ketoprofen may be ascribed at least in part to attenuated IDO levels and immune-inflammatory responses in MDD. Moreover, add-on treatment with ketoprofen may augment the efficacy of sertraline by attenuating IDO. However, these treatments may also significantly reduce the more beneficial properties of T helper-2 and T regulatory (Treg) immune subsets. Future research should develop immune treatments that target the immune-inflammatory response in MDD, while enhancing the compensatory immune-regulatory system (CIRS).

Background: The aim of the present study was to evaluate safety and efficacy of Sri Sri TattvaTM immunity products, a combination of single herb and poly herb formulations in COVID-19 patients by assessing their clinical features and immune markers. The products when administered orally for a period of 14 days in COVID-19 patients demonstrated significant improvement in clinical symptoms.Methods: Patients with fever, cough, sore throat started responding to the treatment from day 3 and most of the patients were clinically free of symptoms by day 7. Early recovery from signs and symptoms was observed in most of the patients. Sri Sri TattvaTM immunity products has also demonstrated an excellent clinical improvement and immune markers including tumor necrosis factor (TNF-alfa), interleukin (IL-6), interferon (IFN-beta), D-dimer, ferritin, lactate dehydrogenease (LDH) and C-reactive protein (CRP) in COVID-19 patients.Results: The final results of this study showed that Sri Sri TattvaTM immunity products reduced the time to clinical cure and number of days in achieving negative real time polymerase chain reaction (RT-PCR) by early viral clearance when given along with standard of care thus reduced the duration of hospitalization.Conclusions: In the present study, 82% of COVID-19 patients cleared the virus within 10-14 days of study period reducing the duration of hospitalization. None of the patients progressed to severe COVID-19 and succumbed to the disease. This clearly indicates that Sri Sri TattvaTM immunity products when administered orally along with standard of care has definitive role in the management of COVID-19 patients.

Brivaracetam ist das neueste zugelassene Antiepileptikum zur Zusatztherapie bei fokalen Epilepsien und besitzt eine hohe Affinitat als SV2A-Ligand. Diese Ubersichtsarbeit fasst die Daten aus den Zulassungsstudien zusammen, in denen mehr als 2000 Patienten Brivaracetam erhielten. Eine signifikante mediane Anfallsreduktion von 30,5–53,1 % fur 50 mg/Tag, 32,5–37,2 % fur 100 mg/Tag und 35,6 % fur 200 mg/Tag konnte nachgewiesen werden. Insgesamt war Brivaracetam gut vertraglich, wobei Fatigue, Schwindel und Somnolenz zu den hauptsachlich auftretenden unerwunschten Ereignissen gehoren. Ein unmittelbarer Wechsel von Levetiracetam auf Brivaracetam in einem Umstellungsverhaltnis zwischen 10:1 bis 15:1 scheint moglich und konnte verhaltensbezogene Nebenwirkungen, die durch Levetiracetam ausgelost wurden, vermindern. Eine zugige Permeabilitat ins Hirngewebe und ein schneller Wirkungseintritt im Vergleich zu Levetiracetam legen nahe, dass Brivaracetam in der Notfallsituation nutzlich sein konnte.

Topiramate has been used increasingly in the management of psychiatric conditions. Clinical trials demonstrated that topiramate augmentation was effective in controlling negative symptoms in schizophrenia. This case report presents a case of a 38-year-old man with schizophrenia who achieved full negative symptom remission upon the adjunctive use of topiramate. However, the remarkable finding of this case is the concomitant decrease in the level of prolactin when topiramate (50 mg/day) was started and the rebound after discontinuation of topiramate. Previous studies stated that topiramate could prevent antipsychotic-induced weight gain and adverse metabolic effects. To the authors' knowledge, no study has reported that topiramate augmentation could be a treatment strategy for antipsychotic-induced hyperprolactinemia. This finding could be verified by well-designed clinical trials.