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A novel, highly sensitive and eco-friendly micellar-mediated spectrofluorimetric method was developed and validated for the determination of the novel antiparkinsonian drug safinamide mesylate in the presence of its related precursor impurity, 4-hydroxybenzaldehyde. The proposed approach relies on increasing the inherent fluorescence emission at 296 nm of safinamide, by forming hydrogen bonds between the mentioned drug and sodium dodecyl sulfate in the micellar system using 0.1 N HCl as a solvent, following excitation at 226 nm. A thorough investigation was conducted into the experimental factors affecting spectrofluorimetric behavior of the studied drug. A linearity plot of safinamide over the concentration range of 10.0-1000.0 ng/mL against the relative fluorescence intensities was established. The proposed method demonstrated excellent sensitivity down to the nano-gram level with detection and quantitation limits of 1.91 and 5.79 ng/mL, respectively. The studied drug was effectively determined in Parkimedine® Tablets. Furthermore, the proposed method allows for ultrasensitive quantification of safinamide in spiked human plasma, with satisfactory percentage recovery (98.97-102.28%). Additionally, the greenness assessment using the advanced green certificate classification approach, the complementary green analytical procedure index (Complex-GAPI), and the analytical GREEness metric approach (AGREE), along with the practicality check using the Blue Applicability Grade Index in addition to the all-inclusive overall whiteness evaluation using the RGB-12 model were carried out. The outcomes demonstrated the effectiveness and whiteness of the proposed technique. Clearly, the suggested approach has the advantages of being simple, requiring no pretreatment steps, and relying solely on direct measuring procedures.

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OBJECTIVE: Several antiseizure medications (ASMs) have been approved for the treatment of focal epilepsy. However, there is a paucity of evidence on direct comparison of ASMs. We evaluated the comparative efficacy and safety of all approved add-on ASMs for the treatment of focal epilepsy using network meta-analysis. METHODS: Data through extensive literature search was retrieved from PubMed, Embase, Cochrane, and ClinicalTrial.gov databases using predefined search terms from inception through March 2023. PRISMA reporting guidelines (CRD42023403450) were followed in this study. Efficacy outcomes assessed were ≥50%, ≥75%, and 100% responder rates. Patient retention rate and safety outcomes such as overall treatment-emergent adverse events (TEAEs) and individual TEAEs were assessed. "Gemtc" 4.0.4 package was used to perform Bayesian analysis. Outcomes are reported as relative risks (RRs) and 95% confidence interval (CI). RESULTS: Literature search retrieved 5807 studies of which, 75 studies were included in the analysis. All ASMs showed significantly higher ≥50% responder rate compared with placebo. Except the ≥75% seizure frequency reduction for zonisamide (2.23; 95% CI: 1.00-5.70) and 100% for rufinamide (2.03; 95% CI: 0.54-11.00), all other interventions showed significantly higher ≥75% and 100% responder rates compared with placebo. Among treatments, significantly higher 100% responder rate was observed with cenobamate compared to eslicarbazepine (10.71; 95% CI: 1.56-323.9) and zonisamide (10.63; 95% CI: 1.37-261.2). All ASMs showed a lower patient retention rate compared to placebo, with the least significant value observed for oxcarbazepine (0.77; 95% CI: 0.7-0.84). Levetiracetam showed a lower risk of incidence (1.0; 95%CI: 0.94-1.1; SUCRA: 0.885067) for overall TEAE compared with other medications. SIGNIFICANCE: All approved ASMs were effective as add-on treatment for focal epilepsy. Of the ASMs included, cenobamate had the greatest likelihood of allowing patients to attain seizure freedom. PLAIN LANGUAGE SUMMARY: This article compares the efficacy and safety of antiseizure medications (ASMs) currently available to neurologists in the treatment of epileptic patients. Several newer generation ASMs that have been developed may be as effective or better than the older medications. We included 75 studies in the analysis. In comparison, all drugs improved ≥50%, ≥75% and 100% responder rates compared to control, except for Zonisamide and Rufinamide in the ≥75% and 100% responder rate categories. Retention of patients undergoing treatment was lower in drugs than placebo. All drugs were tolerated, the levetiracetam showed the best tolerability. Cenobamate more likely help completely to reduce seizures.

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Introduction: The primary objective was to demonstrate the efficacy and safety of itopride as an add-on therapy to a proton pump inhibitor (PPI) in the treatment of gastroesophageal reflux disease. Aim: Reflux disease affects the largest percentage of the population worldwide, symptoms overlap with many other conditions which hamper diagnostic and therapy presenting challenges in treating patients and prompting an intensive search for new, more effective therapeutic regimens. Material and methods: A retrospective study was undertaken with 140 enrolled patients with reflux disease, confirmed by 24-hour pH impedance previously treated with PPIs without any significant improvement. Itopride was added to the PPI therapy in a dose of 150 mg/day, after which the severity of reflux disease symptoms was reassessed. Results: The greatest improvement after the combined treatment (p < 0.001) was experienced in the context of heartburn, nausea and laryngopharyngeal symptoms. There was also a high percentage of statistically significant (p < 0.01) improvement in burning in the oesophagus and stomach and regarding postprandial fullness, gastric retention and swallowing disorders. No adverse effects were noted. Conclusions: The presented study clearly demonstrates that in patients ineffectively treated with PPIs, the addition of itopride to the therapy for 8 weeks without changing the PPI dose, significantly improves the efficacy of treatment of reflux disease and thus shortens the need for medication usage and reduces the costs of therapy, potential side effects of PPI, improves the patient's quality of life and decreases the frequency of medical appointments.

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AIM: To evaluate the efficacy and safety of retagliptin in Chinese patients with type 2 diabetes (T2D) inadequately controlled with metformin. MATERIALS AND METHODS: This multicentre, phase 3 trial consisted of a 16-week, randomized, double-blind, placebo-controlled period, where patients with HbA1c levels between 7.5% and 11.0% were randomized to receive either once-daily (QD) retagliptin 100 mg (n = 87) or placebo (n = 87), both as an add-on to metformin. The primary endpoint was the change in HbA1c from baseline to week 16. RESULTS: At week 16, the least squares mean change in HbA1c from baseline, compared with placebo, was -0.82% (95% CI, -1.05% to -0.58%) for the retagliptin 100 mg QD group (P < .0001) per treatment policy estimand. Significantly higher proportions of patients in the retagliptin 100 mg QD group achieved HbA1c levels of less than 6.5% (11.5%) and less than 7.0% (26.4%) compared with those receiving placebo (0% and 4.6%; P = .0016 and P < .0001, respectively) at week 16. Retagliptin 100 mg QD also lowered fasting plasma glucose and 2-hour postprandial plasma glucose levels. The incidence of adverse events (AEs) during the treatment period was similar between the two groups. However, slightly higher proportions of increased lipase and increased amylase in the retagliptin 100 mg QD group were observed. No patients discontinued treatment permanently because of AEs, and no episodes of severe hypoglycaemia were reported. CONCLUSIONS: Retagliptin 100 mg QD as an add-on therapy to metformin offers a new therapeutic option for treating Chinese patients with T2D inadequately controlled by metformin alone, and is generally well tolerated.

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Objective: This study aimed to assess the treatment compliance, patterns, healthcare resource utilization (HCRU), and costs of anti-epilepsy drugs (AEDs) as the first add-on therapy in patients with epilepsy. Methods: We conducted a retrospective population-based cohort study using Korean National Health Insurance claims data from 2016 to 2020. Patients with epilepsy who newly received AED add-on therapy were identified and followed for up to 12 months to evaluate persistence, adherence, treatment patterns, HCRU, and costs. Results: Among 6,746 patients who initiated AED add-on therapy, 65.5% were persistent on their index AED add-on from the index date until the end of the follow-up period, and the mean persistent time on the index add-on was 307.3 ± 92.3 days. A total of 76.8% patients were adherent, with a medication possession ratio (MPR) ≥80%, and the mean MPR was 88.9 ± 25.4%. Persistence and adherence to the index AED add-on were relatively higher among patients prescribed lamotrigine, levetiracetam, oxcarbazepine, and perampanel than those prescribed carbamazepine, topiramate, or valproate. A total of 41.0% of the patients changed their index AED add-on during the follow-up period. The carbamazepine, topiramate, and valproate groups had higher rates of change than the other AED groups. HCRU and costs tended to be lower in the lamotrigine, levetiracetam, oxcarbazepine, and perampanel groups. Furthermore, perampanel showed the lowest HCRU and costs for all-cause cases as well as the lowest length of stay and outpatient visits for epilepsy-related cases. Conclusion: In this population-based study, the use of lamotrigine, levetiracetam, oxcarbazepine, or perampanel as the first add-on therapy in patients with epilepsy contributed to better treatment compliance and lower HCRU and costs than that of carbamazepine, topiramate, or valproate.

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BACKGROUND: Perampanel (PER) is a newly developed amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptor antagonist that has been globally approved for the treatment of both focal and generalized seizures. The efficacy and safety of PER have only been reported over short periods of treatment so far. This study aims to clarify the long-term efficacy and safety of PER as an add-on therapy. METHOD: This retrospective observational study investigated 176 epilepsy patients who received PER as add-on medical therapy in two Japanese epilepsy centers between June 2016 and July 2022. The adherence, seizure frequency, and plasma concentration of PER were evaluated at three time points: 6 months, 12 months, and 24 months or longer after the start of adjunctive PER treatment. RESULTS: 112 patients undergoing PER treatment were evaluated at 6 months, 86 were evaluated at 12 months, and 52 were evaluated at 24 months or longer. Overall, 42.9 % (48/112), 45.4 % (40/86), and 44.2 % (23/52) of the patients were seizure-free at 6, 12, and 24 months or longer, respectively. The rate of PER tolerance was 78.3 %, 69.9 %, and 54.7 % at 6, 12, and 24 months or longer, respectively. At the latest timepoint, the seizure-free group was taking a significantly lower dose of PER than the seizure-remnant group, and the number of anti-seizure medications (ASMs) was associated with seizure outcomes. In addition, the seizure-free rate was significantly higher in patients who received PER as a first add-on than in those who received it as a late add-on. No significant difference was found in the plasma concentration of PER between the seizure-free and seizure-remnant groups at 24 months or longer. Among the patients receiving PER at dose of 2 mg, however, the plasma concentrations were significantly higher in the seizure-free group than in the seizure-remnant group (282.7 ± 109.8 µg/ml vs 94.7 ± 54.9 µg/ml, p = 0.0024). CONCLUSION: This long-term retrospective observational study provides evidence of the efficacy and safety of PER over 2 years treatment period in Japan. Notably, patients who started on PER as the first add-on showed a better seizure outcome than those who received it as a late add-on over the long term. Measured plasma concentrations may provide valuable guidance for the management of patients. Higher plasma concentration at low dose PER may suggest the better seizure control.

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INTRODUCTION: Overactive bladder symptoms (OABSs) affect patients' quality of life (QOL) worldwide. This pooled analysis compared the efficacy and safety of mirabegron add-on tamsulosin with those of tamsulosin add-on placebo in OABS treatment. METHODS: PubMed, Embase, MEDLINE, and the Cochrane Controlled Trial Register databases were searched for randomized controlled trials (RCTs) examining the efficacy of mirabegron add-on therapy to tamsulosin in the treatment of OABS. Moreover, references from the selected studies were screened. Review Manager 5.4 was used to analyze data. RESULTS: Four RCTs involving 1,397 patients with OABS were selected. Of the total, 697 patients receiving mirabegron add-on tamsulosin constituted the experimental group, and 700 patients receiving tamsulosin add-on placebo constituted the control group. The efficacy endpoints were as follows: mean number of micturition per day (mean difference [MD] = -0.26, 95% confidence interval [CI] = -0.41 to -0.10, p = 0.0001), urgency episodes per day (MD = -0.67, 95% CI = -1.02 to -0.32, p = 0.0002), urgency urinary incontinence (UUI) episodes per day (MD = -0.42, 95% CI = -0.66 to -0.19, p = 0.0005), mean volume voided/micturition (MD = 10.84, 95% CI = 4.97-16.71, p = 0.0003), total International Prostate Symptom Score (IPSS) (MD = -2.01, 95% CI = -4.02 to -0.01, p = 0.05), and IPSS QOL index (MD = -0.65, 95% CI = -0.94 to -0.35, p < 0.0001). Mirabegron therapy, an add-on therapy to tamsulosin, was effective in treating patients with OABS. Moreover, mirabegron might reduce the total IPSS (MD = -2.01, 95% CI = -4.02 to -0.01, p = 0.05). The safety endpoint, treatment-emergent adverse events (odds ratio = 0.94, 95% CI = 0.78-1.13, p = 0.49), suggested that although mirabegron was well-tolerated, it possibly increased the post-void residual urine volume (MD = 10.28, 95% CI = 1.82-18.75, p = 0.02). CONCLUSION: Combination therapy using mirabegron and tamsulosin may be effective in treating patients with non-neurogenic OABS in terms of UUI episodes, total IPSS, and IPSS QOL index. However, its effectiveness must be verified by analyzing additional factors for OABS through further RCTs.

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INTRODUCTION: In theory, combination of two agents, which are suboptimal when given individually, may result in a significant increase in therapeutic effect. Combination therapies have proven particularly effective against infections such as HIV, cancer, and also chronic autoimmune diseases such as rheumatoid arthritis. AREAS COVERED: The authors review the literature, searching for randomized placebo-controlled or comparative, double-blind or investigator-blinded clinical trials, not including open label clinical trials, of treatment of multiple sclerosis (MS) with combination therapy or add-on therapy, including trials of induction therapy, trials for prevention of disease activity or worsening, amelioration of adverse effects, and treatment of relapses, and trials to increase remyelination. EXPERT OPINION: Combination of two platform therapies (Interferon-beta or glatiramer acetate) was without additional effect. Clinical trials with add-on, often applying repurposed drugs (e.g. simvastatin, atorvastatin, minocycline, estriol, cyclophosphamide, azathioprine, albuterol, vitamin D), have been negative, apart from monthly methylprednisolone that, however, had low tolerability. Combination therapy for neuroprotection/remyelination showed some interesting results, though we are still awaiting results of phase III trials. The results of combination of anti-inflammatory therapies have in general been disappointing. In the future, combination of new effective neuroprotective/remyelinating drugs and highly effective anti-inflammatory treatments may benefit people with MS.

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Background: The advancing etiopathogenesis, diagnosis, and treatment of the global coronavirus disease 2019 (COVID-19) pandemic have prompted the medical community to consider Ayurveda, Siddha, and Unani as add-on preventive and therapeutic options. Objective: To explore the effect of standalone or integrative Traditional Formulations (TFs) on selected clinical symptoms and biomarkers of COVID-19. Search strategy: Out of 465 articles identified from PubMed, ScienceDirect, and Scopus, 17 randomized controlled trials (RCTs) with 1646 COVID-19 patients published from January 2020 to February 2022 were included in the study. Inclusion criteria: RCTs that compared the effect of standalone/integrative TFs in decoction, tablet, and powder forms with placebo plus standard care (SC)/placebo/SC as controls involving mild to severe symptomatic COVID-19 patients were included. Data extraction and analysis: Three reviewers independently assessed the titles and abstracts of each article based on the inclusion after deleting duplicates. The relevant full texts were retrieved and examined, and then their data were extracted and double-checked by three independent reviewers using prepared data extraction forms. The primary outcome variables were reverse transcription polymerase chain reaction, fever, cough, dyspnea, myalgia, headache, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and D-dimer. Results: The effect of different TFs or integrative TFs was more to inhibit severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) than the controls. There was an increase in fever and cough, a decrease in dyspnea, myalgia, headache, and ESR, no change in CRP, and a slight increase in D-dimer as an effect of TFs. Conclusions: Integrative or standalone TF may be the inexpensive preventive and therapeutic option to inhibit SARS-CoV-2 and its clinical symptoms.

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Background: Prospective observations on the effectiveness, safety, tolerance, and influence of comorbidity of add-on lacosamide (LCM) therapy are still lacking, especially for domestic generic LCM in China. Objective: In this multicenter real-world study, we aimed to evaluate lacosamide (LCM) as the first add-on therapy in adult Chinese patients with focal epilepsy that had initially been treated with monotherapy. Methods: A cohort of consecutive focal epilepsy patients aged over 16 years were enrolled and followed at the multi-epilepsy centers in China. LCM was prescribed as the first add-on therapy. The main outcome measures included seizure frequency and response rate. Data on seizure-free rate, retention rate, scales of depression and anxiety, and adverse events were also collected as additional outcome measures. Results: A total number of 107 adult subjects (60 men, 56.07%) were enrolled. The mean age was 37.16 ± 15.01 years, and the mean age at seizure onset was 312.35 ± 199.97 months. After the LCM add-on therapy, the ≥50% response rates were 76.19, 81.73, 94.12, and 95.79% at the visit at 4 weeks (visit 2), 8 weeks (visit 3), 16 weeks (visit 4), and 24 weeks (visit 5), respectively, compared to the baseline (visit 1). A total of 34 patients (31.78%) had no seizures during the whole follow-up period. The posttreatment emotional performance of the 97 subjects, defined as generalized anxiety disorder (GAD) and Neurological Disorders Depression Inventory (NDDI) scores, was significantly better than the baseline one. Only one patient suffered from mild dizziness. Conclusion: LCM as the first add-on therapy in adult focal epilepsy in China was effective and safe. Further prospective studies with long-term follow-up periods are needed to confirm our present findings. Clinical trial registration: http://www.chictr.org.cn, ChiCTR2100042485.

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Introduction: The PERMIT study is the largest pooled analysis of perampanel (PER) clinical practice data conducted to date. Methods: This post-hoc analysis of PERMIT investigated the effectiveness, safety and tolerability of PER when used as early add-on therapy (after failure of one or two previous antiseizure medications) in comparison with late add-on therapy (after failure of three or more previous antiseizure medications). Retention and effectiveness were assessed after 3, 6, and 12 months, and at the last visit (last observation carried forward). Effectiveness was assessed by seizure type (total seizures, focal seizures, generalized tonic-clonic seizures [GTCS]) and assessments included seizure freedom rate and responder rate. Safety and tolerability were assessed by evaluating adverse events (AEs) and discontinuation due to AEs. Results: The Full Analysis Set included 1184 and 2861 PWE treated with PER as early and late add-on therapy, respectively. Compared to the late add-on subgroup, the early add-on subgroup was characterized by later mean age at epilepsy onset, shorter mean duration of epilepsy, lower rates of intellectual disability and psychiatric comorbidity, and lower frequency of seizures per month, suggesting a less severe form of epilepsy in this subgroup. After 12 months, retention was significantly higher in the early versus late add-on subgroup (67.7% vs. 62.4%; p = 0.004). At the last visit, responder rates in the early versus late add-on subgroup were significantly higher for total seizures (68.2% vs. 39.3%; p < 0.001), focal seizures (65.0% vs. 36.8%; p < 0.001) and GTCS (83.7% vs. 67.2%; p < 0.001), as were seizure freedom rates (total seizures, 35.9% vs. 11.9% [p < 0.001]; focal seizures, 29.4% vs. 8.7% [p < 0.001]; GTCS, 69.0% vs. 48.1% [p < 0.001]). Incidence of AEs was significantly lower in the early versus late add-on subgroup (42.1% vs. 54.7%; p < 0.001), as was the rate of discontinuation due to AEs over 12 months (15.0% vs. 18.1%; p = 0.031). Discussion: This study demonstrated that PER was effective and generally well tolerated when initiated as early or late add-on therapy, but it was significantly more effective and better tolerated when initiated early. These findings support PER's use as a broad-spectrum, early add-on therapy for use in PWE with focal and generalized seizures.

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Serious manifestations of respiratory virus infections such as influenza and coronavirus disease 2019 (COVID-19) are associated with a dysregulated immune response and systemic inflammation. Treating the immunological/inflammatory dysfunction with glucocorticoids, Janus kinase inhibitors, and monoclonal antibodies against the interleukin-6 receptor has significantly reduced the risk of respiratory failure and death in hospitalized patients with severe COVID-19, but the proportion of those requiring invasive mechanical ventilation (IMV) and dying because of respiratory failure remains elevated. Treatment of severe influenza-associated pneumonia and acute respiratory distress syndrome (ARDS) with available immunomodulators and anti-inflammatory compounds is still not recommended. New therapies are therefore needed to reduce the use of IMV and the risk of death in hospitalized patients with rapidly increasing oxygen demand and systemic inflammation who do not respond to the current standard of care. This paper provides a critical assessment of the published clinical trials that have tested the investigational use of intravenously administered allogeneic mesenchymal stem/stromal cells (MSCs) and MSC-derived secretome with putative immunomodulatory/antiinflammatory/regenerative properties as add-on therapy to improve the outcome of these patients. Increased survival rates are reported in 5 of 12 placebo-controlled or open-label comparative trials involving patients with severe and critical COVID-19 and in the only study concerning patients with influenza-associated ARDS. Results are encouraging but inconclusive for the following reasons: small number of patients tested in each trial; differences in concomitant treatments and respiratory support; imbalances between study arms; differences in MSC source, MSC-derived product, dosing and starting time of the investigational therapy; insufficient/inappropriate reporting of clinical data. Solutions are proposed for improving the clinical development plan, with the aim of facilitating regulatory approval of the MSC-based investigational therapy for life-threatening respiratory virus infections in the future. Major issues are the absence of a biomarker predicting responsiveness to MSCs and MSC-derived secretome and the lack of pharmacoeconomic evaluations.

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OBJECTIVES: To assess the temporal trends in the use of second antiseizure (ASM) regimens and compare the efficacy of substitution monotherapy and combination therapy after failure of initial monotherapy in people with epilepsy. METHODS: This was a longitudinal observational cohort study conducted at the Epilepsy Unit of the Western Infirmary in Glasgow, Scotland. We included patients who were newly treated for epilepsy with ASMs between July 1982, and October 2012. All patients were followed up for a minimum of 2 years. Seizure freedom was defined as no seizure for at least 1 year on unchanged medication at the last follow up. RESULTS: During the study period, 498 patients were treated with a second ASM regimen after failure of the initial ASM monotherapy, of whom 346 (69%) were prescribed combination therapy and 152 (31%) were given substitution monotherapy. The proportion of patients receiving second regimen as combination therapy increased during the study period from 46% in first epoch (1985-1994) to 78% in the last (2005-2015) (RR = 1.66, 95% CI: 1.17-2.36, corrected-p = .010). Overall, 21% (104/498) of the patients achieved seizure freedom on the second ASM regimen, which was less than half of the seizure-free rate on the initial ASM monotherapy (45%, p < .001). Patients who received substitution monotherapy had similar seizure-free rate compared with those who received combination therapy (RR = 1.17, 95% CI: 0.81-1.69, p = .41). Individual ASMs used, either alone or in combination, had similar efficacy. However, the subgroup analysis was limited by small sample sizes. SIGNIFICANCE: The choice of second regimen used based on clinical judgment was not associated with treatment outcome in patients whose initial monotherapy failed due to poor seizure control. Alternative approaches such as machine learning should be explored to aid individualized selection of the second ASM regimen.

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OBJECTIVE: To evaluate the tolerability of clobazam in patients with drug-resistant epilepsy aged 50 years and older. METHODS: We performed a single center, retrospective chart review of patients at least 50 years of age with drug resistant epilepsy of any type who started clobazam as an add on therapy. Retention rate, safety, and tolerability at 6 and 12 months and last follow-up, and the discontinuation rate due to side effects were analyzed. RESULTS: A total of 26 patients met inclusion criteria. Mean age was 62 ± 7.1 years, and 69.2% of patients were female. The mean baseline seizure frequency before initiation of clobazam was 2 (range 1-30) seizures per month. The mean total daily dose of clobazam administered was 13 (range 5 to 30) mg/day. At the 12-month follow-up visit after clobazam initiation, 40% of patients were seizure-free and an additional 45% of patients had > 50% reduction in seizure frequency. The mean seizure frequency at 12-month follow-up was 1.5 (range 0-24) seizures per month. The mean total dose of clobazam at 12-month follow-up was 14.25 (range 5 to 25) mg/day. The mean duration of clobazam at last follow was 55.2 ± 27.02 (mean ± SD months) and 18 (69.2%) patients remained on clobazam. Twenty out of 26 (76.9%) patients reported at least one side effect and 6/26 (23%) discontinued the medication within a month of initiation. At last follow-up, 40% remained seizure free on stable dosing. CONCLUSION: Clobazam can be a safe and tolerable, add-on treatment older adults with drug-resistant epilepsy. Those who responded tolerated the medication well. Discontinuation due to side effects occurred soon after initiation of therapy.

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OBJECTIVE: To examine the efficacy and safety of Curalin supplement in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: Adult patients with type 2 diabetes were randomized 1:1 to receive Curalin supplement or placebo. The primary endpoint was HbA1c decrease at 1 month. The secondary endpoint was a decrease in HbA1c by more than 0.5% and 1% and a change in 7 daily blood glucose measurements. A satisfaction questionnaire was used as an exploratory endpoint. Safety variables and adverse events were assessed. RESULTS: After 1 month of intervention, HbA1c was reduced by 0.94% in the Curalin arm versus 0.4% in the placebo arm (P = 0.008). 72% of Curalin patients had decreased HbA1c levels >0.5% versus 35% in the placebo arm (P < 0.05). The Treatment Satisfaction Questionnaire indicated that Curalin arm patients reported higher overall satisfaction. CONCLUSIONS: Curalin treatment significantly reduced HbA1c over a 1-month period and was well-tolerated.

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BACKGROUND AND PURPOSE: Neuromyelitis optica spectrum disorder (NMOSD) is a severe neurological inflammatory disease mainly caused by pathogenic aquaporin-4 antibodies (AQP4-IgG). The safety and efficacy of the neonatal Fc receptor antagonist batoclimab addition to conventional intravenous methylprednisolone pulse (IVMP) therapy in patients with NMOSD acute attacks was assessed. METHODS: In an open-label, dose-escalation phase 1b study, NMOSD patients with acute myelitis and/or optic neuritis received four doses of weekly subcutaneous injections of either 340 mg or 680 mg batoclimab with concurrent IVMP and were followed up for 27 weeks. The primary end-points were safety and tolerability. Secondary end-points included pharmacodynamics and efficacy, with key efficacy assessment at week 4. RESULTS: In total nine NMOSD patients were enrolled, including two and seven in the 340 and 680 mg groups. Five patients had acute myelitis, while the remaining four had unilateral optic neuritis. Batoclimab add-on therapy had an overall good safety profile without serious adverse events. In the 680 mg group, mean immunoglobulin G (IgG) reached its maximum reduction at the last dose (day 22). In the meantime, AQP4-IgG was undetectable in six of seven subjects whose baseline AQP4-IgG titers ranged from 1:32 to 1:320. Expanded Disability Status Scale score was reduced by 1.3 ± 0.4 at week 4 (2.7 ± 1.3) compared with baseline (4.0 ± 1.0). CONCLUSIONS: Batoclimab add-on therapy to IVMP is safe and tolerated in patients with NMOSD. Preliminary evidence suggests a beneficial neurological effect. A randomized controlled trial would be needed to prove the efficacy.

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AIM: To evaluate the efficacy and safety of janagliflozin in Chinese patients with type 2 diabetes (T2D) inadequately controlled with metformin monotherapy. MATERIALS AND METHODS: This multicentre phase 3 trial included a 24-week, randomized, double-blind, placebo-controlled period, followed by a 28-week extension period. Patients (N = 421) with HbA1c of 7.0% or higher and 10.5% or less were randomized (1:1:1) to receive once-daily placebo, janagliflozin 25 or 50 mg. After the 24-week treatment period, patients on placebo were re-randomized (1:1) to janagliflozin 25 or 50 mg for the additional 28-week treatment, whereas patients on janagliflozin maintained the same therapy. The primary endpoint was the change from baseline in HbA1c to week 24. RESULTS: At week 24, the placebo-adjusted least squares mean changes of HbA1c were -0.58% and -0.58% with janagliflozin 25 and 50 mg, respectively (P < .0001 for both). The proportion of patients achieving HbA1c less than 7.0% was higher with janagliflozin 25 and 50 mg compared with placebo (41.8%, 41.7% and 28.0%, respectively). Both janagliflozin doses provided significant reductions in fasting plasma glucose, 2-hour postprandial glucose, body weight and systolic blood pressure, and improvements in high-density lipoprotein cholesterol and insulin sensitivity compared with placebo (P < .05 for all). The trends in improvement of these variables were retained during the 28-week extension period. No severe hypoglycaemia occurred throughout the whole 52-week treatment. CONCLUSIONS: Janagliflozin 25 or 50 mg once-daily added to metformin therapy significantly improved glycaemic control, reduced body weight and systolic blood pressure, improved high-density lipoprotein cholesterol and insulin sensitivity, and was generally well-tolerated by Chinese T2D patients who had poor glycaemic control with metformin monotherapy.

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Background: Numerous randomized controlled trials (RCTs) conducted in China have shown that jinlida granules are a promising traditional Chinese medicine (TCM) for the treatment of persons with type 2 diabetes mellitus (T2DM). Controversial results have been reported in different RCTs. The aim of our study was to evaluate the adjuvant hypoglycemic effect of jinlida granules on persons with T2DM and to explore the source of heterogeneity between these RCTs. Materials and methods: Medical article databases were individually searched by two authors for RCTs that provided data regarding the effect of jinlida granules in the treatment of T2DM before 1 June 2022. The methodological quality of the included RCTs was comprehensively assessed by two authors. Data from RCTs with low risk of bias were pooled using Stata SE 12.0 (random-effects model). Evidence derived from the meta-analysis will be assessed according to the GRADE system. Results: Twenty-two RCTs were eventually included in the systematic review and three RCTs with low risk of bias were analyzed in the meta-analysis. Compared with the control groups, significant changes were found in lowering glycosylated hemoglobin a1c (mean difference -0.283 with 95% CI -0.561, -0.004; P=0.046), and were not found in lowering 2-hour postprandial glucose (mean difference -0.314 with 95% CI -1.599, 0.972; P=0.632) and fasting blood glucose (mean difference -0.152 with 95% CI -0.778, -0.474; P=0.634) in the jinlida groups. The GRADE-assessed evidence quality for the outcomes was moderate. Conclusion: The adjuvant hypoglycemic effect of jinlida granules on adult Chinese persons with T2DM was statistically found in lowering HbA1c and was not statistically found in lowering FPG and 2h-PG. Evidence grading should be considered moderate, and the results should be interpreted cautiously. Whether the efficacy of HbA1c-lowering related to clinical significance remains to be investigated in future RCTs. Differences in HbA1c, FPG and 2h-PG at baseline and high risk of bias were important source of heterogeneity between these RCTs. In order to objectively evaluate the efficacy of jinlida granules on T2DM, it is urgently needed that high-quality RCTs evaluating the hypoglycemic effect of jinlida granules in the treatment of qi-yin deficiency pattern T2DM. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42018085135.

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Background: The coronavirus disease 2019 (COVID-19) is a novel coronavirus that causes severe infection in the respiratory system. Since the immune status plays an essential role in combating COVID-19, herbal medicines, which have an immunomodulatory effect, may help prevent and even treat COVID-19. Nigella sativa is one of the herbal medicines with antiviral and immunomodulatory activities, and its therapeutic effectiveness makes it a promising add-on therapy for COVID-19. In addition, vitamin D3 has an immunomodulatory role, but the effect of therapeutic vitamin D3 supplementation in SARS-CoV-2 infection is still not well-known. Objective: This study aims to investigate the effects of Nigella sativa and vitamin D3 as single supplemental therapies and in combination on viral clearance indicated by a negative polymerase chain reaction and the alleviation of symptoms during the study follow-up duration of 14 days. Patients and Methods: The study design was an open-label randomized controlled clinical trial conducted at the Respiratory Hospital at the Kobry El Qobba Armed Forces Medical Complex. In total, 120 COVID-19 patients with mild to moderate symptoms were randomly assigned to four groups, with thirty patients each, as follows: Group 1 received an oral dose of 900 mg Nigella sativa through 450 mg soft gelatin capsules twice daily for two weeks; Group 2 received 2,000 IU of vitamin D3 through 1000-IU tablets given as two tablets, once daily; Group 3 received 900 mg of Nigella sativa and 2,000 IU of vitamin D3 in the same manner of dosing as in the previous groups; and Group 4 was the control group. All groups received standard therapy for COVID-19 infections and clinical management of COVID-19's clinical symptoms. Results: The Nigella sativa-vitamin D3 combination in addition to the standard therapy for COVID-19 infections significantly contributed to the alleviation of most COVID-19 symptoms: 50% of patients were free of cough after 7 days, 70% showed an absence of fatigue after 4 days, 80% had no headache after 5 days, 90% were free of rhinorrhea after 7 days, and 86.7% of the patients had no dyspnea after 7 days. Moreover, patients in the four studied groups showed a reduced median temperature after 3 days of treatment. Negative results of the polymerase chain reaction (PCR) test recorded on the 7th and 14th day of therapy were superior in the Nigella sativa and vitamin D3 combination arm compared to those of the other studied arms where the value of the odds ratio (OR) on the 7th day was 0.13 with 95% CI: 0.03-0.45 and that of the 14th day was 0.09 with 95% CI: 0.02-0.3. Conclusion: The results of this study showed a promising therapeutic benefit of the administration of Nigella sativa and vitamin D3 combination in COVID-19 patients with mild to moderate symptoms. Additionally, the remarkable viral clearance in a short time interval and reduction in the severity and progression of symptoms recommended the use of this combination as an add-on therapy for the management of COVID-19 patients. Clinical Trial Registration: ClinicalTrials.gov, Identifier: NCT04981743.

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OBJECTIVE: Perampanel (PER) has previously been shown to be effective and tolerable when used as an adjunctive therapy for patients with focal-onset seizures (FOS). This study aimed to evaluate the effect of PER as adjunctive therapy for patients with FOS in the Chinese population under real-world conditions for 1 year. METHODS: A prospective, single-center, 1-year observational study was conducted at Huashan Hospital, enrolling both under age (≥4 years old) and adult patients with FOS. Response to PER was assessed at 3-, 6-, and 12-month checkpoints by analyzing the 50 % responder rate, the seizure-free rate, and reduction in seizure frequency. RESULTS: One hundred and eight patients (mean age: 26.6 years, 56.5 % males) with FOS were included, with seventy-six patients finishing the 1-year follow-up (retention rate: 70.4 %, mean PER dose: 4.3 mg/day). The seizure frequency was reduced significantly at 3, 6, and 12 months relative to baseline (p < 0.001 for each seizure type). At 12 months, the responder rate was 65.8 %, and the seizure-free rate was 39.5 %. A significantly higher responder rate was found in patients with focal to bilateral tonic-clonic seizures (p = 0.024), among which the percentage of patients with sleep-related epilepsy was significantly high (p = 0.045). Responders had a lower number of concomitant anti-seizure medications (ASMs) than the non-responders (p = 0.009). Drug-related adverse events (AEs) were reported in 37 % of patients, mostly mild or moderate, and the patients who experienced AEs had a higher daily dose of PER than those who did not (p = 0.026). CONCLUSION: Perampanel, an add-on therapy for focal-onset seizures, was found to be effective and tolerable in Chinese patients at 12 months.

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