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Antiepileptic drug; Cannabinoid; Epilepsy Fármaco antiepiléptico; Cannabinoide; Epilepsia Fàrmac antiepilèptic; Cannabinoide; Epilèpsia Objective: We assessed the efficacy, safety, and tolerability of cannabidivarin (CBDV) as add-on therapy in adults with inadequately controlled focal seizures. Materials and Methods: One hundred and sixty-two participants (CBDV n=81; placebo n=81) were enrolled. After a 4-week baseline, participants titrated from 400 to 800 mg CBDV twice daily (b.i.d.) (or placebo) over 2 weeks, followed by 6 weeks stable dosing (at 800 mg b.i.d.) and a 12-day taper period. The primary endpoint was the change from baseline in focal seizure frequency during the 8-week treatment period. Secondary endpoints included additional efficacy measures relating to seizures, physician- and participant-reported outcomes, change in the use of rescue medication, cognitive assessments, and safety. Results: Median baseline focal seizure frequencies were 17–18 per 28 days in both groups, and similar reductions in frequency were observed in the CBDV (40.5%) and placebo (37.7%) groups during the treatment period (treatment ratio [% reduction] CBDV/placebo: 0.95 [4.6]; confidence interval: 0.78–1.17 [−16.7 to 21.9]; p=0.648). There were no differences between the CBDV and placebo groups for any seizure subtype. There were no significant treatment differences between CBDV and placebo groups for any of the secondary efficacy outcome measures. Overall, 59 (72.8%) of participants in the CBDV group and 39 (48.1%) in the placebo group had ≥1 treatment-emergent adverse event (AE); the 3 most common were diarrhea, nausea, and somnolence. The incidence of serious AEs was low (3.7% in the CBDV group vs. 1.2% in the placebo group). There was little or no effect of CBDV on vital signs, physical examination, or electrocardiogram findings. Elevations in serum transaminases (alanine aminotransferase or aspartate aminotransferase) to levels >3×upper limit of normal occurred in three participants taking CBDV (two discontinued as a result) and one taking placebo; however, none met the criteria for potential Hy's Law cases. Conclusion: It is likely the 40.5% seizure reduction with CBDV represents an appropriate pharmacological response in this population with focal seizures. The placebo response was, however, high, which may reflect the participants' expectations of CBDV, and a treatment difference from placebo was not observed. CBDV was generally well tolerated. The trial was sponsored by GW Research Ltd.

Jonas Mortensen,1 Sune Møller Skov-Jeppesen,1,2 Peter Bill Juul Ladegaard,1 Lars Lund1,2 1Department of Urology, Odense University Hospital, Odense, Denmark; 2Institute of Clinical Research, University of Southern Denmark, Odense, DenmarkCorrespondence: Jonas MortensenDepartment of Urology, Odense University Hospital, Sdr. Boulevard 29, Odense, 5000, DenmarkTel +45 40172260Email Jonas.Mortensen2@rsyd.dkPurpose: The aim of this study was to investigate whether ESWT with a higher energy as an add-on therapy to vacuum-pump followed by manipulation exercises could reduce the penile curvature, pain and improve IIEF-5 score.Materials and Methods: Men aged > 18 and < 80 years and diagnosed with PD in stable phase with no history of penile surgery or previous ESWT treatment were eligible to participate. They were randomised to either active ESWT (n = 16) or sham ESWT (n = 16). Both groups were treated once a week for five weeks. Each treatment session consisted of 2000 shockwaves at 0.5mJ/mm2. All patients in both groups used a vacuum pump followed by manipulation exercises.Results: Thirty men completed the study protocol. Mean age in the treatment group was 61.7 (SD 8.3) and 63 (SD 7.35) in the control group. After six months, mean change in penile curvature was − 12.8 (SD 13) degrees in the treatment group and − 6.6 (SD 8.9) in the control group (p = 0.204). Mean IIEF-5 score decreased by 0.17 (SD 3) in the treatment group and 3.06 (SD 5.5) in the control group (p = 0.086) at six-month follow-up. Pain was assessed using both VAS and PDQ and demonstrated no difference between the groups after six months (p = 0.648).Conclusion: In the treatment group, we observed a greater but non-significant change in penile curvature and no adverse effects.Keywords: Peyronie’s disease, ESWT, vacuum pump, erectile dysfunction, manipulation exercises

Dapagliflozin is the first novel SGLT2 inhibitor for the treatment of Type 2 diabetes. The aim of this study was to evaluate its effectiveness and safety in a real-life clinical setting. We analyze data from four hospitals on patients initiated on dapagliflozin. HbA1c, weight and daily insulin dosage was recorded at baseline and 6 months follow-up.229 patients received dapagliflozin. At baseline, mean HbA1c was 82mmol/mol(186) and mean weight was 102 kg(n=159).The average reduction in HbA1c at 6 months (n=121) was 13mmol/mol whereas the average reduction in weight(n=96) was 2kg.A mean reduction in daily insulin requirement(n=41) by 12 units(13%) at 6 months compared to baseline was noted. Nine patients developed candidiasis, eight developed UTI, five reported symptoms of thirst and five developed hypoglycaemia out of which four were on insulin and one on gliclazide. Ten patients discontinued(4%) dapagliflozin due to side effects. Our results confirm that dapagliflozin can be used safely and effectively in a real-life setting. Keywords: Dapagliflozin, real world, SGLT2, Type 2 diabetes. Continuous...

To investigate the efficacy and safety of vibegron add-on therapy in men with persistent storage symptoms receiving α-1 blockers or PDE5 inhibitor for benign prostatic hyperplasia and then determine the independent factors affecting the efficacy of vibegron.Vibegron 50 mg was administered for 12 weeks to 42 patients (72.0 ± 8.2 years) with persistent storage symptoms who had taken α-1 blockers (22 patients) or PDE5 inhibitor (20 patients). The primary endpoint was change in the overactive Bladder (OAB) Symptom Score from baseline to end of treatment. The secondary endpoints were changes in each question of several questionnaires, maximum flow rate and residual urine volume. Finally, independent factors affecting the efficacy of vibegron were investigated.Total OAB Symptom Score was significantly decreased (6.21 ± 3.12 vs 4.38 ± 2.46; P.001). Although each score of several questionnaires, especially for storage symptoms, improved significantly, no significant improvement was found in stress incontinence, straining, bladder pain and urethral pain in the Core Lower Urinary Tract Symptom score. Maximum flow rate and residual urine volume did not change, and no patient discontinued vibegron because of adverse events. Multiple regression analysis showed that OAB Symptom Score, Core Lower Urinary Tract Symptom score, prostate volume and monotherapy with α-1 blocker were independent factors affecting the efficacy of vibegron.Add-on therapy of vibegron to monotherapy with α-1 blockers or PDE5 inhibitor for patients with benign prostatic hyperplasia and persistent storage symptoms was effective and safe.

Background: Cardiovascular complications are one of the leading causes of global mortality. Statins are intended to produce beneficial effects in reducing the risk of morbidity and mortality in cardiovascular patients. However, it becomes negligible in statin intolerant patients mainly due to muscle related symptoms. Objective: The objective of the study is to summarize the results of the studies available on safety and efficacy of bempedoic acid/ezetimibe combination treatment in statin intolerant patients. Methods: After comprehensive literature survey, in Cochrane Library, PubMed, Embase and Medline, randomized controlled studies involving statin intolerant hyperlipidemia, patients with low- density lipoprotein ≥200 mg/dl and at high risk of cardiovascular disease treated with Bempedoic acid and ezetimibe combination were selected. Results: For final quality analysis two clinical trials were selected to assess the safety and efficacy of the combination of Bempedoic acid and Ezetimibe. Data shows Bempedoic acid and Ezetimibe combination significantly lowered the low-density lipoprotein compared to the control groups (placebo vs Bempedoic acid vs ezetimibe). In addition, the data shows significant reduction in highly sensitive C- reactive protein, non-high density lipoprotein cholesterol, total cholesterol and apolipoprotein B. Conclusion: Overall, we conclude that the combination of Bempedoic acid and Ezetimibe can be considered as a treatment of choice for the treatment of hyperlipidemia for patients with statin-intolerance or maximally tolerated even to low-dose statins.

Men with lower urinary tract symptoms (LUTS) treated with α-blockers may experience overactive bladder (OAB) symptoms and receive antimuscarinic drugs. Mirabegron (B3-adrenoreceptor agonist) is an alternative add-on therapy, that has been shown to be more effective than placebo in improving OAB symptoms. Superior results observed for tamsulosin plus mirabegron in mean volume voided per micturition, urgency episodes per day, and total urgency and frequency score. Higher rates of drug related treatment emergent adverse events were noted with tamsulosin plus mirabegron. The results of PLUS reveal the utility of mirabegron and tamsulosin therapy in the treatment of men with benign prostatic hyperplasia who developed symptoms of overactive bladder. The MATCH study confirmed that combination therapy for 12 weeks in men with symptoms of LUTS and OAB was more effective than placebo and was well tolerated.

Objectives: To compare the role of low dose Theophylline and Tiotropium rotacap in improving the lung functions and day to day life of patients suffering from COPD. Study Design and Setting: A Clinical trial study was conducted at Department of Pharmacology and Therapeutics, BMSI in association with Department of Chest Medicine, JPMC. Methodology: This study was planned as an open label and parallel clinical trial study. A total of 168 patients of COPD were selected for this study and only 161 patients completed the 3 months duration of the study. The enrolled patients were grouped into 2, namely A and B. Tab. Theophylline 350 mg was given to Group A in two divided doses while Tiotropium rotacap18µg through rotahaler was given to group B once a day. Results: Mean FEV1 ± SD was improved by 0.04 ± 0.02 in Theophylline therapy group while by 0.07 ± 0.01 in the Tiotropium therapy treated group and a significant difference between the changes in the two treatment groups was evident. There was a percentage improvement in PEFR of 8.9 ± 5.8 in the Theophylline therapy treated group and of 13.2 ± 4.7 in Tiotropium therapy treated group. When Tiotropium group was compared with Theophylline group for improvement in percentage change in PEFR from day 0, a significant difference was evident between the two groups. There was a significant improvement from day 0 in CAT score in Tiotropium treated groups versus Theophylline group after 3 months of therapy. Conclusion: Tiotropium rotacap was more effective as compared to low dose Theophylline in improving pulmonary functions and CAT score in patients with COPD

Asthma is a genuine worldwide medical condition influencing all age gatherings, with expanding pervasiveness in many agricultural nations, rising therapy costs, and a rising weight for patients and the local area. Hypersensitive components have been involved for asthma in 50–80% of patients and these rates are additionally relevant to patients with serious asthma. This examination planned to survey clinical results of omlizumab treatment; asthma control, decrease of asthma seriousness and compounding and specific consideration regarding medical clinic, ICU stays and oral steroid organization. Planned associate examination directed on 32 subjects with serious unfavorably susceptible uncontrolled bronchial asthma. Omalizumab was given subcutaneous, at regular intervals or month to month as indicated by changed necessities while past asthma medicine not diminished or halted. Asthma control appraisal, asthma seriousness appraisal, medical clinic stay, ICU stay, and oral steroid organization prior to beginning omalizumab and 1, 3, 6 months subsequent to beginning omalizumab therapy were assessed and recorded. Following a half year of omalizumab organization their was considerable improvement of FEV1/FVC and FEV1 with critical decrease of uncontrolled cases, and huge decrease in severity.Likewise generous improvement of asthma intensifications, medical clinic affirmations, ICU confirmations and recurrence of oral steroid organization following a half year of omalizumab organizations. Omalizumab showed great outcomes for its utilization in patients with serious hypersensitive asthma, and aided in progress of lung capacities, asthma control , asthma seriousness, and decrease of asthma intensifications , ICU confirmations and use of fundamental steroid.

Objective: Traumatic brain injury (TBI) is the number one cause of death under 44 years of age; in spite of this fact, there is no standard available pharmacological agent for the treatment of brain injury. We evaluated the effectiveness of magnesium sulfate treatment for the management and outcome of TBI. Material and Methods: The prospective cases (n = 60) of TBI were included with non-probability consecutive sampling. They received standard protocol treatment for TBI and magnesium sulfate as an add on therapy. GCS was noted on two occasions, at the time of admission and on the 3rd day. T-test was used to compare the results and for identification of significance/insignificance results. Results: Mean age of the patients was 37.12 ± 13.25 years. Majority were male (68.3%), while females were 31.7%. Mean duration of an elapsed post traumatic brain injury was 5.06 ± 2.32 hours. Mean GCS before magnesium sulfate treatment (on admission) was 5.46 ± 1.521; mean Glasgow coma (GCS) after magnesium sulfate treatment (on 3rd day) was 8.03 ± 2.56. There existed a significant difference between the GCS scores at the time of admission and on 3rd day (p value < 0.0001). Mean GCS was 7.69 ± 2.55 in age < 30 years and it was 8.29 ± 2.57 in age > 30 years, but this difference was not statistically significant. Conclusion: A significant improvement was found in the GCS after magnesium sulfate therapy in patients with TBI.

COVID-19 has affected negatively day to day life and global economy. Considering need for search of immunity modulator drugs for fighting this virus, Ayurvedic treatment was planned. 30 year old female patient, having history of the hypertension was diagnosed as a case of COVID-19 through RT-PCR. AYUSH Kwath (20 ml OD for 7 days), Sanshamani vati(2BD for 7 days), Sudarshan churn (3gm for14 days), Vit –C and Azithromycin given orally for 5 days. RT-PCR sample result was found COVID negative on 7th day of treatment. Antipyretic, anti-inflammatory, immune-modulatory activities were documented earlier of used medications which have shown beneficial result in present case also. Orally administered, add on Ayurvedic formulation exerted symptomatic relief in symptomatic COVID-19 case with pitta-kapha prakriti having co-morbidity of Hypertension. RCT needs to be conducted to validate result in larger sample which will generate evidence for support.

To evaluate the cost-effectiveness of mepolizumab added to standard of care (SOC) compared with SOC alone among patients with severe uncontrolled eosinophilic asthma in the Singapore setting. A Markov model with three health states (asthma on mepolizumab and SOC, asthma on SOC alone, and death) was developed from a healthcare system perspective over a lifetime horizon. During each 4-week cycle, patients in the non-death health states could experience asthma exacerbations requiring oral corticosteroid burst, emergency department visit, or hospitalization. Asthma-related mortality following an exacerbation or all-cause mortality could also occur at each cycle. The model was populated using local costs while utilities were derived from international literature. Transition probabilities were obtained from a mixture of Singapore-specific and internationally published data. The base-case analysis comparing mepolizumab plus SOC with SOC alone resulted in an incremental cost-effectiveness ratio (ICER) of SGD335 486 (USD238 195) per quality-adjusted life-year (QALY) gained. Sensitivity analysis demonstrated that the ICER was most sensitive to the price of mepolizumab, followed by the proportion of exacerbations which required hospital intensive care. Despite restricting mepolizumab use to patients with a higher baseline exacerbation rate (3 in the past year) in a scenario analysis, the ICER remained high at SGD238 876 (USD 169 602) per QALY gained. At its current price, mepolizumab is not considered a cost-effective use of healthcare resources in Singapore. Substantial price reductions for mepolizumab are required to improve its cost-effectiveness to an acceptable range. These results will be useful to inform national funding decisions.

Background Aspirin-exacerbated respiratory disease (AERD) affects 7% of asthmatics. Usual therapies are inadequate for asthma and/or nasal polyposis, leading to decreased quality of life. Objective Our objective was to evaluate the efficacy of dupilumab in AERD patients with uncontrolled, chronic rhinosinusitis with nasal polyposis (CRSwNP). Methods Patients 18 years and older with a physician diagnosis of AERD and sino-nasal outcome test 22 (SNOT 22) score ≥19 despite standard medical therapy were eligible for the study. Patients received one month of placebo dosing, followed by 6 months of dupilumab. Patients were blinded to the order of therapy. Wilcoxon-paired rank sum test was used to compare study outcomes at baseline and the completion of the study. Results Ten patients completed the study. The median baseline SNOT 22 score improved from 46 [IQR: 34 to 64.8] to 9.5 [IQR: 2.5 to 19] after 6 months of therapy (p = 0.0050). The median baseline Lund MacKay score improved from 21.5 [IQR: 17 to 23.3] to 4 [IQR: 1.2 to 6] after 6 months of therapy (p = 0.0050). There was also improvement in the following secondary outcomes: asthma control test (ACT), mini asthma quality of life questionnaire (AQLQ), and University of Pennsylvania Smell Identification test (UPSIT). Exhaled nitric oxide (FeNO), total serum IgE, 24-hour urinary leukotriene E4, and serum thymus and activation regulated cytokine (TARC) also decreased. There were no significant study-related adverse events. Conclusion Dupilumab was highly effective as add-on therapy for CRSwNP in AERD, improving patient-reported outcomes, sinus opacification, and markers of T2 inflammation.

With the recent advancement in immuno-oncology, next-stage early oncology development is focusing on identifying the best combinations of established immunotherapies with new agents to either overc...

Background: Influenza, or flu, is a respiratory illness that is caused by a virus. As Influenza is known to be highly contagious and there by affecting working community at large, a natural; cost effective remedy can help sail through the course of illness with much ease. The plant Cymbopogon citratus (DC) Stapf. commonly known as Lemon grass belongs to Poaceae family and is a native of tropical countries. Various studies have been done on the plant to reveal its potential therapeutic effects. Thus this study untended to evaluate its efficacy in the management of Influenza and its symptoms. Methodology: Randomized double blind placebo controlled clinical study. 62 patients of age group 20- 50 years, suffering from Influenza and fulfilling the diagnostic criteria were selected and randomly grouped into trial (Group I - 31 patients) and control group (Group II - 31 patients received the Placebo- Distilled water 25ml 3 times daily). Both the groups were given Paracetamol 500mg/kg body weight as rescue medicine if required. Observation & Results: The signs and symptoms of Influenza which were exhibited in patients when subjected to the Trial medication showed good results. The quality of life in them was better compared to control group. Conclusion: The current study helped to confirm the effect of the plant Cymbopogon citratus (DC) Stapf. in influenza. In Trial group, significantly better remission of associated signs and symptoms of influenza was found compared to control group. This would help us create an increased awareness amongst the public about the use of herbal medicines in either cure or as add on therapy in the management of Influenza.

Safinamide is a reversible and selective monoamine oxidase-B (MAO-B) and sodium channel inhibitor with demonstrated efficacy in mid-to late-stage Parkinson's disease (PD) as an adjunct to l-DOPA. This study aimed to confirm the efficacy and safety of safinamide in PD patients with wearing-off.This 24-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study included Japanese PD patients with wearing-off on l-DOPA treatment. Patients were randomized to receive placebo (P), safinamide 50 mg/day (S50), or safinamide 100 mg/day (S100). The primary endpoint was the change from baseline in mean daily ON-time without troublesome dyskinesias (ON-time). Other measures included the changes in mean daily OFF-time, the unified Parkinson's disease rating scale (UPDRS) score, and the PDQ-39 summary index.A total of 406 subjects were randomized, of whom 349 completed the study. Baseline characteristics were balanced. Differences in the change of mean daily ON-time at Week 24 compared with the P group were 1.39 h (p = 0.0002) in the S50 group and 1.66 h (p 0.0001) in the S100 group. Changes from baseline in mean daily OFF-time, UPDRS Part II total score (OFF phase), UPDRS Part III total score (ON phase), and UPDRS Part I also showed significant improvements. Adverse events occurred in 58.9%, 60.2%, and 61.4% of the P, S50, and S100 groups, respectively. The most common adverse drug reactions were dyskinesias (2.1%, 8.3%, and 10.6%) and visual hallucinations (1.4%, 3.0%, and 4.5%).As an adjunct to l-DOPA, safinamide safely increased ON-time and improved PD symptoms/signs in PD patients with wearing-off.

Objective: The present study was conducted to investigate the effect of Viola odorata extracted syrup on the quality and patterns of sleep in patients with depression or obsessive–compulsive disord...

BACKGROUND Nucleos(t)ide analog (NA) has shown limited effectiveness against hepatitis B surface antigen (HBsAg) clearance in chronic hepatitis B (CHB) patients. AIM To evaluate the efficacy and safety of add-on peginterferon α-2a (peg-IFN α-2a) to an ongoing NA regimen in CHB patients. METHODS In this observational study, 195 CHB patients with HBsAg ≤ 1500 IU/mL, hepatitis B e antigen (HBeAg)-negative (including HBeAg-negative patients or HBeAg-positive patients who achieved HBeAg-negative after antiviral treatment with NA) and hepatitis B virus-deoxyribonucleic acid < 1.0 × 102 IU/mL after over 1 year of NA therapy were enrolled between November 2015 and December 2018 at the Second Affiliated Hospital of Xi’an Jiaotong University, China. Patients were given the choice between receiving either peg-IFN α-2a add-on therapy to an ongoing NA regimen (add-on group, n = 91) or continuous NA monotherapy (monotherapy group, n = 104) after being informed of the benefits and risks of the peg-IFN α-2a therapy. Total therapy duration of peg-IFN α-2a was 48 wk. All patients were followed-up to week 72 (24 wk after discontinuation of peg-IFN α-2a). The primary endpoint was the proportion of patients with HBsAg clearance at week 72. RESULTS Demographic and baseline characteristics were comparable between the two groups. Intention-to-treatment analysis showed that the HBsAg clearance rate in the add-on group and monotherapy group was 37.4% (34/91) and 1.9% (2/104) at week 72, respectively. The HBsAg seroconversion rate in the add-on group was 29.7% (27/91) at week 72, and no patient in the monotherapy group achieved HBsAg seroconversion at week 72. The HBsAg clearance and seroconversion rates in the add-on group were significantly higher than in the monotherapy group at week 72 (P < 0.001). Younger patients, lower baseline HBsAg concentration, lower HBsAg concentrations at weeks 12 and 24, greater HBsAg decline from baseline to weeks 12 and 24 and the alanine aminotransferase ≥ 2 × upper limit of normal during the first 12 wk of therapy were strong predictors of HBsAg clearance in patients with peg-IFN α-2a add-on treatment. Regarding the safety of the treatment, 4.4% (4/91) of patients in the add-on group discontinued peg-IFN α-2a due to adverse events. No severe adverse events were noted. CONCLUSION Peg-IFN α-2a as an add-on therapy augments HBsAg clearance in HBeAg-negative CHB patients with HBsAg ≤ 1500 IU/mL after over 1 year of NA therapy.

Background/purpose: Rituximab is effective in treating pemphigus both as the first-line treatment and as an add-on treatment for refractory disease. A high rate of relapse among patients receiving rituximab means that maintenance therapy is frequently required. Therefore, we aimed to evaluate the use of azathioprine as maintenance therapy for patients receiving rituximab and to investigate the efficacy and safety of one or multiple cycles of rituximab treatment. Methods: We retrospectively collected data regarding pemphigus patients treated with rituximab from 2008 to 2015 with at least one year of follow-up at a referral center in Northern Taiwan. The medical records and clinical data were reviewed to determine the efficacy and complication rate of the treatment. Results: A total of 78 pemphigus patients were identified. Ninety-one percent of the patients achieved complete remission after the first cycle of rituximab with a relapse rate of 67.9%. Repeated cycles of rituximab showed a trend to shorten the time to next complete remission and to reduce the rate of subsequent relapses. The adverse events were usually not severe and were manageable. Use of azathioprine significantly prolonged the duration of remission (21.98 ± 16.24 vs. 9.98 ± 7.93 months, P = 0.0232). This effect of azathioprine usage remained after univariate and multivariate logistic regressions. Conclusion: This study provides an insight that azathioprine could serve as a good choice of maintenance therapy for patients receiving rituximab. The efficacy and safety of rituximab remain favorable even with repeated administration. Keywords: Azathioprine, Maintenance, Pemphigus, Rituximab

Background: Increasing rates of behavioral problems among children in India necessitates newer ways of managing them with medical and nonmedical approaches. Music add-on therapy is a method for treating mental disturbances. This study examines the effectiveness of music add-on therapy in managing children with behavioral problems. Methods and Materials: A randomized controlled design was adopted with a random allocation of 40 children (20 each in experimental and control groups) aged between 6 and 12 years with behavioral disorders as per the International Statistical Classification of Diseases and Related Health Problems (ICD)-10. After the pretest, both the groups received treatment as usual (TAU), while the experimental group alone additionally received music add-on intervention with eight Hindustani ragas for 3 weeks. As clinical outcome measures, we used the Childrens Global Assessment Scale, Nisonger Child Behavior Rating Form typical IQ (NCBRF-TIQ) version, and visual analogue scale (VAS) for a parent to monitor the behavioral improvement. Results: Children exposed to the music add-on therapy had improved score in the Children Global Assessment Scale (CGAS) and the VAS as compared with the control group (F [2,76] = 34.307, P < 0.001 and F [2,76] = 72.4, P < 0.001, respectively). Further, the NCBRF-TIQ version revealed improvement in positive social behavior (F [2,76] = 13.089, P < 0.001) and reduction in problem behaviors in the experimental group. Conclusion: Music add-on therapy is effective in improving positive social behavior and reducing problem behaviors among children.

[No abstract available]

INTRODUCTION Dupilumab is a recombinant human IgG4 monoclonal antibody that inhibits IL-4 and IL-13 signaling. This drug raises concerns about the economic impact in scenarios with constrained resources. This study aimed to estimate the cost-utility of dupilumab plus standard care (SoC) vs SoC alone in adolescents and adults with severe asthma and eosinophilic phenotype. METHODS A probabilistic Markov model was created to estimate the cost and quality-adjusted life-years (QALYs) of patients with uncontrolled allergic asthma in Colombia. Total costs and QALYs of standard therapy (ICS + LABA), add-on therapy with dupilumab, were calculated over a lifetime horizon. Multiple sensitivity analyses were conducted. Cost-effectiveness was evaluated at a willingness-to-pay (WTP) value of $19,000. RESULTS The base-case analysis showed dupilumab was associated with higher annual annual per-patient costs (US$5,719 for dupilumab and US$1,214 for standard therapy) and higher QALYs than standard therapy (fe 4.06 QALYs vs 3.97 QALYs, respectively). . The incremental cost-effectiveness ratio estimated was US$50,160 per QALY gained. CONCLUSION Dupilumab is not cost-effective using a WTP of US$19000 per QALY threshold in Colombia. Our study provides evidence that should be used by decision-makers to improve clinical practice guidelines and should be replicated to validate their results in other middle-income countries.

Pregabalin is increasingly being used as a first-line treatment for symptomatic control of restless legs syndrome (RLS). This study aimed to evaluate the efficacy and safety of pregabalin as add-on therapy in RLS patients already taking dopamine agonists (DA) but still in need of further management. Patients with idiopathic RLS were enrolled, and all had already been prescribed DA for at least 3 months but still had either persistent symptoms, side effects, or comorbid insomnia. An initial dose of 75 mg pregabalin was begun, adjusted as needed, and maintained at a stable dose for 4 weeks, followed by observation for a total of 8 weeks. RLS symptoms and insomnia scores were evaluated before and after add-on pregabalin treatment. Patients were monitored for side effects that could be attributed to pregabalin. A total of 32 RLS patients were enrolled, and 20 subjects remained until the endpoint. After the pregabalin add-on, the mean IRLS score showed significant improvement compared to the baseline (p < 0.001). The insomnia severity index score also improved (p = 0.036), and no serious adverse effects were observed. Our preliminary data suggests the potential for pregabalin as an add-on therapy to DA with regards to both efficacy and safety in patients who have inadequate RLS improvement.

Objective: To investigate whether respiratory therapy (RT) increases pain if inhaled lidocaine can attenuate pain increase in infants and children undergoing surgery for congenital heart disease (CHD). Design: Double-blind, randomized, placebo-controlled trial. Setting: Pediatric intensive care unit in a Brazilian tertiary-care, university hospital. Patients: 119 patients < 18 years submitted to open-heart surgery for CHD. Interventions: Aerosolized lidocaine (1 mg/kg) before RT maneuvers and tracheal suction, compared to placebo. Measurements and main results: Pain was assessed by the face, legs, activity, cry, consolability pain scale - revised (FLACC-R), along with hemodynamic and ventilatory parameters, before and after RT and tracheal suction on postoperative days 1, 3, and 7. Lidocaine or placebo were administered right before RT. RT induced minor changes in pain, which were not attenuated by lidocaine (confirmed in multivariate analysis). RT also induced minor, not clinically relevant effects in hemodynamic and ventilatory parameters, which were also not modified by lidocaine. Conclusions: Respiratory therapy did not increase postoperative pain in patients after pediatric congenital heart surgery up to the 7th day, nor aerosolized lidocaine exhibited any clinically significant effect on pain or other hemodynamic or ventilatory parameters. Objetivo: Investigar se a fisioterapia respiratória aumenta a dor, se a lidocaína inalada pode atenuar o aumento da do rem bebês e crianças submetidos à cirurgia para cardiopatia congênita. Métodos: trata-se de um estudo duplo-cego, randomizado e controlado por placebo. Local: Unidade de terapia intensiva pediátrica de um hospital universitário brasileiro de atenção terciária. Pacientes: foram inclusos 119 pacientes

Background Obesity, insulin resistance, renal dysfunction, hyperuricemia are some of the most common causes of resistant hypertension (RH). A close relationship exists between RH and fluid retention. Currently, there is no consensus regarding pathogenetic therapy of RH and there are no studies on the effects of sodium–glucose cotransporter-2 (SGLT2) inhibitors in obese patients with RH and chronic kidney disease (CKD). The aim was to evaluate the effects of dapagliflozin (D) in obese P with RH and CKD stages 3a. Methods 45 obese P (mean body mass index (BMI) 34.2 kg/m2, waist circumference (WC) 104 cm) with true RH and CKD 3a (eGFR 45–59 mL/min/1.73m2) were included in the study under conventional therapy full doses of appropriate combinations (mean 3.7 antihypertensive drugs). The D at daily doses of 10 mg was added to previous treatment. The blood pressure (BP) was measured in the office and by ambulatory BP monitoring. Anthropometry, metabolic profile, including oral glucose tolerance test with insulin, homeostatic model assessment HOMA-R, hematocrit (Hct), uric acid, potassium (K), serum creatinine, calculated GFR were performed at baseline and after 12 weeks treatment. Results At baseline were excellent correlations between BMI and SBP (r=0.45, P After 12 weeks administration of D, the mean 24 h ambulatory BP effectively decreased (−7.6/−4.3 mmHg; P By linear regression analysis, the independent associated factor for the change SBP was baseline BMI (P Conclusion Dapagliflozin shows an additional antihypertensive effect when added to the prior combination therapy in obese patients with RH and CKD 3a without risk of hyperkalemia. Dapagliflozin increase hematocrit, possibly due to its diuretic effects and hemoconcentration. So, positive antihypertensive effect D is due to natriuretic effect and decrease fluid retention. Furthermore, there is also a strong indication that the BP effect is also influenced by weight loss and dapagliflozin administration decreased body mass index, waist circumference, fasting glucose and uric acid, with a tendency to decrease the insulin resistance without changes in insulin secretion. Funding Acknowledgement Type of funding sources: None.

Chronic urticaria is in some cases very difficult to treat, we aimed to evaluate the effect of colchicine on chronic urticaria management. Fifty-five euthyroid patients with chronic urticaria were examined based on UQL and UAS7 questionnaires. The overall UQL-Q score after three months has not any statistical difference between groups. The overall UQL-Q score changes between groups was not statistically different. However, the UQL-Q score significantly reduces during study period in each group. In conclusion, colchicine can manage the sign and symptoms of chronic urticaria which improve the patients' quality of life. This article is protected by copyright. All rights reserved.

The authors have withdrawn this manuscript because they found a serious issue in data-analysis which leads to wrong interpretation of the results. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.

Metformin is the first-line therapy for the treatment of type 2 diabetes (T2D) through mechanism of reduction in hepatic glucose production and fasting plasma glucose. Dorzagliatin is a novel glucokinase activator (GKA) that improves glucose and insulin sensitivity which significantly reduces post meal plasma glucose. Combination of dorzagliatin with metformin would offer benefits through the synergy of two mechanisms. In this randomized, double-blind, placebo-controlled phase 3 trial (NCT03141073), the efficacy and safety of dorzagliatin add-on to metformin in T2D patients were assessed. Eligible T2D patients (n=767) were randomly assigned in a 1:1 ratio to dorzagliatin group or placebo group add-on to metformin (1500 mg/day) for a 24-week double-blind treatment, then followed by a 28-week open-label treatment with dorzagliatin in all patients. The primary efficacy endpoint was the change from baseline in the glycated hemoglobin(HbA1c) level at week 24 and the safety was assessed throughout the trial. At week 24, the HbA1c was reduced from baseline in dorzagliatin group, superior to placebo (-1.02% vs. -0.36%; ETD, -0.66%; 95% CI, -0.79 to -0.53; P

Introduction: Diabetes is characterized by chronic hyperglycemia and disturbances of carbohydrate, lipid and protein metabolism. This study is an attempt to show an improvement in lipid profile (TC, TG, LDL and HDL) in patients of type 2 diabetes mellitus who were previously on metformin monotherapy with uncontrolled diabetes. Material and method: A total of 30 patients were enrolled who were on metformin monotherapy and with uncontrolled diabetes. Patients were given metformin 500 mg twice a day and saxagliptin 2.5 mg once a day. Patients were followed up at 1st, 3rd and 6th month and lipid profile (TC, TG, LDL and HDL) estimation was done during the follow up period. Results: The mean age ± SD in male and female patients was 61.42 yrs ± 6.99 and 55.93 yrs ± 5.74 respectively. The mean change in value from baseline at 24 weeks was TC = 9.66%, TG = 9.40%, LDL = 14.87%, HDL = 5.63%. A highly significant difference has been seen at 0 v/s 1, 0 v/s 3 and 0 v/s 6 months in TC, TG, LDL and HDL values. Conclusion: Saxagliptin has shown an improvement in lipid profile (TC, TG, LDL, HDL) during 6 months of treatment in patients of type 2 DM. Keywords: Saxagliptin, Uncontrolled type 2DM, Metformin, Lipid profile.

Objective: Teneligliptin is a novel, highly selective dipeptidyl peptidase-4 inhibitor. The objective of the present study was to investigate the efficacy and safety of teneligliptin as add-on therapy in patients with type 2 diabetes mellitus (T2DM) who are inadequately controlled by conventional therapy (metformin/glimepiride) in India. Methods: Clinical study protocol was approved by the Institutional Ethics Committee. T2DM patients (male/female) whose glycated hemoglobin (HbA1c) >7% were randomized to receive following group treatments, namely, Treatment A: Metformin/glimepiride plus add-on teneligliptin 20 mg and Treatment B: Metformin/glimepiride for 24 weeks. A pre-designed case report form was used to collect information from the prescribing physicians regarding the efficacy and safety of teneligliptin. Efficacy variables included change in plasma blood glucose (fasting and postprandial) and HbA1c from baseline to week 24. Treatment emergent adverse events were assessed. Results: A total of 120 type 2 diabetes patients were analyzed. Teneligliptin as add-on therapy with metformin/glimepiride significantly reduced plasma glucose (HbA1c, fasting, and postprandial) concentration as compared to conventional therapy. Conclusion: Add-on therapy with teneligliptin was found superior over conventional therapy in reducing plasma glucose concentration (fasting and postprandial) and HbA1c levels significantly in patients with T2DM. Further, it was found effective and well tolerated in Indian patients with T2DM who are inadequately controlled with conventional therapy.

Allicin as add-on therapy for Helicobacter pylori infection: A systematic review and meta-analysis

BACKGROUND: According to several phase III studies, tiotropium [a long-acting muscarinic antagonist (LAMA)] is a well-tolerated add-on therapy to inhaled corticosteroids (ICS) for asthmatics with or without the addition of long-acting beta2-agonists (LABAs). However, real-world studies based on clinical phenotypes to predict the long-term need of tiotropium as an add-on therapy for asthmatics are limited. METHODS: This is a retrospective study conducted at a single medical center in Taiwan from July 2016 to July 2018. An asthma control test (ACT) is applied to uncontrolled asthmatics to evaluate the effectiveness of tiotropium as an add-on therapy. Asthmatic subgroups with different clinical phenotypes and needing long-term tiotropium as a maintenance treatment are identified. The effectiveness of tiotropium add-on therapy is defined as an improvement of ACT score ≥3 points 3 months after the treatment (vs. baseline), while the long-term requirement of tiotropium is defined as tiotropium dependency >1 year. RESULTS: The study analyzed a total of 160 uncontrolled asthmatics regardless of low- or medium-to-high-dose ICS plus LABA. One hundred and twelve patients responded well (ACT score increased ≥3 points) to tiotropium. These patients were further divided into two subgroups: one with tiotropium add-on therapy for ≥1 year due to patients’ difficulties in stepping down from tiotropium; the other with tiotropium add-on therapy for 30 kg/m(2) were predictors for asthmatics requiring long-term tiotropium add-on therapy. CONCLUSIONS: Tiotropium add-on therapy is effective for uncontrolled asthmatics. Moreover, patients with ACO, initial FEV1% predicted 30 kg/m(2) require long-term tiotropium add-on therapy for asthma control.

Objective To evaluate the long-term efficacy of mirabegron add-on therapy in patients with spinal cord injury (SCI) based on an urodynamic study. Methods This retrospective study involved a chart audit of individuals with SCI who underwent two consecutive urodynamic studies between April 1, 2015 and April 1, 2018. After adding 50 mg of mirabegron once a day to the pre-existing antimuscarinic therapy for a period of, at least 6 months, the following variables were analyzed: change in cystometric capacity, change in bladder compliance, change in maximal detrusor pressure, change in reflex volume, and presence of significant leakage during filling cystometry. Results A total of 31 participants with a mean age of 41±15 years were included in the analysis. A significant increase in cystometric capacity (mean, 362 to 424 mL; p=0.03), reflex volume (mean, 251 to 329 mL; p=0.02), and bladder compliance (median, 12 to 18 mL/cmH2O; p=0.04) was observed. The presence of leakage during filling cystometry was significantly reduced (29% to 10%; p=0.03). Likewise, a non-significant decrease in the change in maximal detrusor pressure was observed (mean, 31 to 27 cmH2O; p=0.39). Conclusion Adding mirabegron to conventional antimuscarinics further improved urodynamic parameters in patients with chronic SCI, and sustained efficacy was observed in long-term use.

Addition of peginterferon alpha (PEG-IFN add-on) to entecavir (ETV) treatment after a short lead-in phase results in more response than ETV monotherapy in HBeAg-positive chronic hepatitis B infection (CHB). This study is the first to assess long-term efficacy of this treatment strategy. Patients who received ETV ± 24 weeks of PEG-IFN add-on in a global trial (ARES study) and completed follow-up were eligible to participate in this observational LTFU study if they had at least one combined HBeAg and HBV DNA measurement beyond week 96 of the ARES study. The primary endpoint was combined response (HBeAg loss and HBV DNA

BACKGROUND Diffuse fasciitis with psoriatic arthritis on magnetic resonance imaging (MRI) has not been previously described in childhood. Here we present the first case report of a pediatric patient developing fasciitis, beyond plantar fasciitis, with psoriatic arthritis. CASE SUMMARY An 11-year-old female was admitted with the complaints of psoriatic rash on the body associated with severe pain in the lower extremities and arthritis in the right knee. Psoriasis was confirmed by skin biopsy, she diagnosed with juvenile psoriatic arthritis. Diagnostic tests did not indicate any pathology except MRI. MRI of the femur and tibia revealed that high-signal inflammatory changes in the subdermal fascia. These findings led to a diagnosis of psoriatic fasciitis. Methotrexate was given for 3 mo but the patient showed no response to therapy; therefore, etanercept was added. However, there was no response to treatment. Etanercept was switched to adalimumab at the sixth month of therapy. Clinical improvement started with therapy of adalimumab within one month. Fasciitis finding in MRI disappeared at seventh months on adalimumab therapy. She has no complaint for two years with adalimumab. CONCLUSION The most effective imaging method is MRI and adalimumab may be the best choice of treatment for psoriatic fasciitis. © The Author(s) 2019.

This protocol for a Cochrane Review is out of date and has been withdrawn in order to adhere to Cochrane policy.

The novel dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist tirzepatide (TZP) is in development for type 2 diabetes (T2D). Efficacy and safety of once weekly TZP vs. semaglutide (SEMA) was assessed in people with T2D on background metformin. In this open-label, 40-wk Phase 3 study, people with T2D (N=1879; mean baseline [BL] HbA1c 8.28%; age 56.6 y; T2D duration 8.6 y; BMI 34.2 kg/m2) were randomized (1:1:1:1) to TZP (5, 10, 15 mg) or SEMA (1 mg). Primary efficacy objective was noninferiority of TZP 10 and/or 15 mg vs. SEMA for mean change in HbA1c from BL at 40 wk. Secondary objectives included noninferiority (TZP 5 mg) for HbA1c change and superiority (all TZP doses) for change in HbA1c, body weight (BW) and fasting serum glucose (FSG), and proportion of patients with HbA1c Disclosure J. Frias: Consultant; Self; 89bio, Inc., Altimmune, Axcella Health Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Gilead Sciences, Inc., Intercept Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk, Pfizer Inc., Sanofi, Research Support; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Bristol-Myers Squibb Company, CymaBay Therapeutics, Eli Lilly and Company, Intercept Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., Madrigal Pharmaceuticals, Inc., Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk, Pfizer Inc., Sanofi, Speaker’s Bureau; Self; Merck & Co., Inc., Sanofi. M. J. Davies: Advisory Panel; Self; Boehringer Ingelheim International GmbH, Boehringer Ingelheim Limited (UK), Eli Lilly and Company, Lexicon Pharmaceuticals, Inc., Novo Nordisk A/S, Sanofi, Other Relationship; Self; AstraZeneca, NIHR Leicester Biomedical Research Centre, Novo Nordisk, Speaker’s Bureau; Self; Astra Zeneca Pharma India Ltd, Boehringer Ingelheim (China), Boehringer Ingelheim (Philippines), Inc., Boehringer Ingelheim International GmbH, Boehringer Ingelheim Limited (UK), Boehringer Ingelheim Saudi Arabia Trading, Boehringer Ingelheim Singapore Pte. Ltd, Boehringer Ingelheim Sp. Z o. o., Eli Lilly and Company, Napp Pharmaceuticals, Novo Nordisk, Novo Nordisk A/S, S. C. Sanofi Romania SRL, Sanofi K. K. J. Rosenstock: Board Member; Self; Applied Therapeutics, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Intarcia Therapeutics, Inc., Novo Nordisk, Oramed Pharmaceuticals, Inc., Sanofi, Consultant; Self; Applied Therapeutics, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Intarcia Therapeutics, Inc., Novo Nordisk, Oramed Pharmaceuticals, Inc., Sanofi, Research Support; Self; Applied Therapeutics, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Genentech, Inc., Intarcia Therapeutics, Inc., Lexicon Pharmaceuticals, Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk, Oramed Pharmaceuticals, Inc., Pfizer Inc., REMD Biotherapeutics, Sanofi. F. C. Perez manghi: None. L. Fernandez lando: Employee; Self; Eli Lilly and Company, Stock/Shareholder; Self; Eli Lilly and Company. B. Bergman: Employee; Self; Eli Lilly and Company, Employee; Spouse/Partner; Eli Lilly and Company. B. Liu: Employee; Self; Eli Lilly and Company, Stock/Shareholder; Self; Eli Lilly and Company. X. Cui: Employee; Self; Eli Lilly and Company. K. Brown: Employee; Self; Eli Lilly and Company. Funding Eli Lilly and Company

Background and Aims Belimumab (BLM), a recombinant human IgG-1λ monoclonal antibody directed against B-cell activating factor (BAFF), is the first approved biological agent for patients with active severe systemic lupus erythematosus (SLE) and lupus nephritis (LN). There is clinical evidence that combining belimumab with B cell depleting therapy can ameliorate disease activity in severe, refractory SLE patients. Although BLM is a B cell directed therapy and has been shown to significantly decrease total B cells, flow cytometry observations suggest a rapid increase of circulating memory B cells. The present study investigated the dynamics of B cell subsets in patients treated with or without BLM, with a special focus on the memory compartment in order to assess the characteristics of these memory B cells. Method We first performed extensive B cell subset phenotyping by high sensitivity flowcytometry according to the Euroflow protocol on whole blood from active lupus nephritis or SLE patients with other major organ involvement treated with standard of care (SOC) consisting of high dose steroids and mycophenolate mofetil combined with or without the addition of BLM. Next we characterized memory B cell gene expression profiles with single-cell RNA and V(D)J sequencing (ScRNA-SEQ). Results By employing high sensitivity flowcytometry, we established that the absolute increase in circulating memory B cells in SLE and LN patients was significant for patients who initiated BLM but not for patients treated with standard of care (Figure 1). The increase was observed in a broad range of memory B cell subsets (Unswitched, IgG1+, IgG2+, IgA1+, IgA2+) at 2 and 4 weeks following initiation of BLM treatment. This rise in memory B cells could hypothetically be attributed to either proliferation or homeostatic modulation of tissue-resident memory B cells causing a release into the circulation. ScRNA-SEQ cell cycle gene-expression was performed and established in both groups a non-proliferating phenotype [in approximately ∼94%] of memory B cells post-treatment, including absence of MKI67 as active proliferation marker. Additionally, BLM treatment did not result in an increased, and even in a severe reduction of the largest memory B cells clones after two weeks. In contrast, no change in clonality was seen after treatment with SOC. Together these data indicate that proliferation is not likely to be responsible for the observed increase in memory B cells by BLM. Furthermore, a clear difference was found in gene-expression levels between both treatment groups: BLM was responsible for the upregulation of 72 vs 10 genes in SOC, likewise 162 vs 32 genes were downregulated. Most importantly, a significant downregulation of the migration genes SELL (CD62L), CCR7, ITGB1, RAC2 and ICAM2, were specifically seen in BLM treated patients, possibly reflecting disrupted lymphocyte trafficking preventing memory B cells to either transmigrate into tissue or be retained at the tissue level. Conclusion The addition of BLM compared to standard of care in SLE patients leads to an increase of memory B cells in the circulation which appeared independent of proliferation. The process was accompanied with a strong modulation of gene-expression levels including a reduced expression of migration markers pointing towards disrupted lymphocyte trafficking. Altogether, these data could have important implications to further improve treatment strategies in severe SLE or lupus nephritis patients, for instance by establishing a deeper depletion of (autoreactive) memory B cells by the addition of rituximab after the initiation of belimumab.