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Objective: This study investigated the efficacy of adjunctive low-frequency repetitive transcranial magnetic stimulation (rTMS) compared to sham stimulation for treating psychogenic non-epileptic seizures (PNES) in children and adolescents. Methods: Twenty patients diagnosed with PNES were randomized to receive either active rTMS or sham stimulation over the supplementary motor area (SMA) for ten sessions over two weeks. Clinical severity, seizure frequency and duration, dissociative experiences, anxiety, and depression were assessed before, after treatment, and at two weeks follow-up. Results: Both groups showed improvements in clinical parameters. However, the active rTMS group demonstrated a significantly greater reduction in overall clinical severity compared to sham at the four-week follow-up. This improvement was not sustained after treatment ended. Additionally, patients with more severe PNES (higher seizure frequency and duration) showed greater improvement with rTMS. There were no significant differences between groups in anxiety or depression scores. Conclusion: Low-frequency rTMS may offer some benefits for PNES, particularly for patients with severe symptoms. However, the short-lived effects and potential for placebo response necessitate further research with larger sample sizes, longer follow-up periods, and optimized stimulation parameters. [ABSTRACT FROM AUTHOR]

Aims: To evaluate the efficacy, safety, and tolerability of adjunctive lacosamide therapy against focal seizures in young children (1 month – 4 years). Methods: This non‐randomized, open‐label, and self‐controlled real‐world study included 105 children (1 month–4 years) with focal seizures treated with adjunctive lacosamide therapy at Children's Hospital of Chongqing Medical University. Results: (1) The 50% response rates at 3, 6, 9, and 12 months of follow‐up were 58.1%, 61.0%, 57.1%, and 56.2%, while the seizure‐free rates were 27.6%, 34.3%, 32.4%, and 37.1%, respectively. The 50% response rate of the first addition of lacosamide for focal seizures was much higher than the second and later added treatment at 3 months (p = 0.038). After 1 year of follow‐up, these children showed an improvement in neurodevelopmental levels (p < 0.05). (2) Lacosamide retention rate was 72.7% (64/88) after 1 year of follow‐up. Lack of efficacy and serious adverse events were independent risk factors for the lacosamide retention rate. (3) During adjunctive lacosamide therapy, 13 (12.4%) patients reported adverse events and five (4.7%) patients withdrew due to adverse events, including vomiting drowsiness, ataxia (0.94%), neck itching with eczema (0.94%), irritability (1.88%), and gastrointestinal discomfort (0.94%). Conclusion: Adjunctive lacosamide therapy was effective, safe, and well‐tolerated in young Chinese children with focal seizures in this study. [ABSTRACT FROM AUTHOR]

Objective: Describe the presenting features, surgical procedure, and clinical outcomes of two cats managed with marginal resection and photodynamic therapy (PDT) for eyelid squamous cell carcinoma (SCC). Animals Studied: A 12‐year‐old female spayed domestic shorthair cat (case 1) and a 10‐year‐old female spayed domestic shorthair cat (case 2). Procedures: Following marginal resection of the eyelid neoplasm, hemostasis was achieved using a handheld cautery unit then 1 mL of infracyanine green was injected into the surgical wound bed. Photodynamic therapy was performed using an 810 nm diode laser in two consecutive steps: (i) six cycles at 500 mW for 30 s per cycle, using a rapid movement; then (ii) one (case 1) or two cycles (case 2) of 30 s at 2000 mW, using a slow deliberate movement to effect (charred surface). Results: Histopathology was consistent with SCC resected with incomplete margins in both cats. Follow‐up duration was 416 and 161 days in case 1 and case 2, respectively. Consecutive exams and photo‐documentation (in clinic or by owners) showed appropriate healing of the lower eyelid, with a smooth lid margin, and no evidence of tumor regrowth or ocular irritation. Subtle trichiasis was noted in case 1 on day 185, but not at the last follow‐up. Conclusions and Clinical Relevance: Marginal resection followed by PDT may be a valid alternative to complete surgical resection of periocular SCC in cats. The procedure was easy to perform, post‐operative recovery was uncomplicated, and neither cat developed recurrent disease during the follow‐up period. [ABSTRACT FROM AUTHOR]

Objective: To determine the efficacy and safety of perampanel (PER) as an adjunctive therapy in children aged 4–12 years with epilepsy. Methods: We performed a non-randomized, open-label, placebo-uncontrolled, real-world self-controlled study that included 216 young children (aged 4–12 years) with epilepsy who received PER as adjunctive therapy at the children's hospital affiliated with Chongqing Medical University from July 4, 2020, to September 20, 2023. Results: (1) The efficacy rates of adjunctive PER therapy at 3, 6, 9, and 12 months were 62.8%, 67.8%, 65.3%, and 61.2%, respectively. PER showed efficacy in alleviating focal seizures, generalized tonic–clonic seizures, myoclonic seizures, and absence seizures. The efficacy rates for variants of self-limited epilepsy with centrotemporal spikes (SeLECTS) and Lennox-Gastaut syndrome (LGS) were 89.5% and 66.7%, respectively. (2) Focal non-motor onset seizures with or without impaired awareness, focal to bilateral tonic–clonic seizures (FBTCS), LGS, variants of SeLECTS, the number of concomitant antiseizure medications (ASMs), a family history of epilepsy, and focal lesions on cranial magnetic resonance imaging were independent factors affecting efficacy. The order of PER addition did not affect efficacy. The retention rates at 3, 6, 9, and 12 months were 90.7%, 84.7%, 74.7%, 64.9%, respectively. (3) Adverse reactions occurred in 45 patients (45/216, 20.8%), with irritability/aggressive behavior (18/216, 8.3%) and somnolence (14/216, 6.5%) being the most common. Twelve patients (12/216, 5.6%) withdrew from the study because of adverse reactions. Conclusion: In young Chinese children with epilepsy, PER is effective, safe, and well-tolerated as an adjunctive therapy, making it a viable option for use with broad-spectrum ASMs. [ABSTRACT FROM AUTHOR]

Junyu Chen,1,&ast; Yupei Yuan,2,&ast; Ying Hu,1 Liang Liang1,3 1Department of Psychology, The Fourth Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, People’s Republic of China; 2Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, People’s Republic of China; 3Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, Hubei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Liang Liang, Department of Psychology, The Fourth Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, People’s Republic of China, Tel +8609915848029, Email 79023556@qq.comBackground: The adjunctive therapeutic potential of simvastatin in schizophrenia treatment has generated interest due to its anti-inflammatory and neuroprotective properties. This meta-analysis aims to assess the efficacy of simvastatin as an adjunct treatment for schizophrenia, synthesizing results from various controlled trials.Methods: We performed a comprehensive search of databases including PubMed, Embase, and the Cochrane Library for randomized controlled trials (RCTs) evaluating the efficacy of simvastatin as an adjunct therapy in patients with schizophrenia. The primary outcome measures were improvements in the Positive and Negative Syndrome Scale (PANSS) scores. Secondary outcomes included changes in overall clinical condition and level of functioning. Data were pooled using random-effects models, and heterogeneity was assessed through I² statistics.Results: The four RCTs included in the analysis represented 425 participants. The combined results demonstrated no significant advantage of simvastatin over placebo in reducing PANSS total scores with a pooled effect size (Standard Mean Difference, SMD) of − 0.36 (95% Confidence Interval, CI: − 0.82 to 0.11) at 1 month, and − 1.80 (95% Confidence Interval, CI: − 4.82 to 1.21) at 3 months, indicating minimal to no effect. Similarly, analyses of secondary outcomes showed no significant improvements in overall clinical condition and level of functioning. The studies exhibited low heterogeneity (I² = 0%).Conclusion: This meta-analysis provides evidence that simvastatin, used as adjunctive therapy, does not significantly improve the symptomatic outcomes of schizophrenia compared to placebo. Although simvastatin is well-tolerated, its role in enhancing antipsychotic treatment efficacy in patients with schizophrenia appears limited. These findings suggest that simvastatin should not be recommended as an adjunctive treatment in the clinical management of schizophrenia. Further research may explore the potential subgroups that could benefit from such treatment or identify the biological reasons for the lack of efficacy.Keywords: schizophrenia, simvastatin, adjunctive therapy, meta-analysis, randomized controlled trials, efficacy

Introduction: Periodontitis is a chronic inflammatory disease that leads to the destruction of both the hard and soft tissues of the periodontium. Various herbal extracts can be used as a Local Drug Delivery (LDD) agent to suppress the inflammation caused by micro-organisms. Aim: To evaluate the effectiveness of a hydrogel based on mustard seed extract as an adjunct to Non-surgical Periodontal Therapy (NSPT) for the treatment of chronic periodontitis. Materials and Methods: This pilot interventional study was conducted at Saveetha Dental College and Hospitals, Chennai between June 2023 and July 2023. The study included a total of 30 participants diagnosed with chronic periodontitis who were divided into two groups: group A (n=15) received only Scaling and Root Planing (SRP), while group B (n=15) received SRP along with 0.5% mustard seed extract hydrogel. Baseline and two-week post-operative assessments included recording of Gingival Index (GI), Plaque Index (PI), and modified Sulcus Bleeding Index (mSBI). The data was analysed by Statistical Package for Social Sciences (SPSS), software version 23.0 for windows. An independent t-test was conducted to assess significance between the two groups, while the comparison of baseline and post-operative variables within each group was done using a paired t-test. A p-value of

Context: Morinda citrifolia L. (Rubiaceae), commonly known as noni, is widely used as a complementary and alternative therapy in many countries due to its numerous beneficial effects on health. Aims: To thoroughly analyze the efficacy and safety of M. citrifolia fruit across all reported areas. Methods: The articles were explored on the PubMed and Cochrane Library databases using a combination of keywords: Morinda citrifolia AND human studies; Morinda citrifolia AND pharmacological activities using PRISMA guidelines. Results: Studies in animal models revealed its activity as anti-dyslipidemia, anti-lipogenesis, anti‑fungal, hepatoprotective, hypotensive, immunostimulatory, anti-alopecia, photoprotective, antitumor, antiviral, anticancer, antidopaminergic, and antimicrobial. Based on the clinical and efficacy evidence, it is apparent that M. citrifolia is a potentially valuable medicinal plant whose status should be upgraded from laboratory bench to bedside. The safety of M. citrifolia has been confirmed and proven by no occurrence of AEs or only mild gastrointestinal discomforts. However, five cases of male and female patients aged from 14 to 63 years old reported different symptoms, such as fatigue, headache, vomiting, pigmentation, or acute hepatitis, after a high-dose daily use of this supplement. Conclusions: Taking everything into consideration, M. citrifolia, despite its mild adverse events, has a beneficial efficacy and safety as an antioxidant; nevertheless, caution and therapy drug monitoring is required if this plant is to be taken in a long-term period.

Abstract Aims Sodium tanshinone IIA sulfonate (STS) injection has been widely used as adjunctive therapy for pulmonary heart disease (PHD) in China. Nevertheless, the efficacy of STS injection has not been systematically evaluated so far. Hence, the efficacy of STS injection as adjunctive therapy for PHD was explored in this study. Methods Randomized controlled trials (RCTs) were screened from China Science and Technology Journal Database, China National Knowledge Infrastructure, Wanfang Database, PubMed, Sino-Med, Google Scholar, Medline, Chinese Biomedical Literature Database, Cochrane Library, Embase and Chinese Science Citation Database until 20 January 2024. Literature searching, data collection and quality assessment were independently performed by two investigators. The extracted data was analyzed with RevMan 5.4 and STATA 14.0. Basing on the methodological quality, dosage of STS injection, control group measures and intervention time, sensitivity analysis and subgroup analysis were performed. Results 19 RCTs with 1739 patients were included in this study. Results showed that as adjunctive therapy, STS injection combined with Western medicine showed better therapeutic efficacy than Western medicine alone for PHD by increasing the clinical effective rate (RR = 1.22; 95% CI, 1.17 to 1.27; p

Background: To evaluate the methodological quality, report quality, and evidence quality of meta-analysis (MA) and systematic review (SR) on the efficacy of probiotics in the treatment of rheumatoid arthritis (RA). Methods: Databases were used to identify eligible SRs/MAs until February 12, 2024. The methodological quality of the studies was assessed using AMSTAR-2 tool, the quality of the literature reports was scored using PRISMA checklists, and the quality of the evidence was graded using GRADE system. Methods: Databases were used to identify eligible SRs/MAs until February 12, 2024. The methodological quality of the studies was assessed using AMSTAR-2 tool, the quality of the literature reports was scored using PRISMA checklists, and the quality of the evidence was graded using GRADE system. Conclusions: Probiotics may have a therapeutic effect on RA, based on the evidence provided by the SRs/MAs in this overview. Nevertheless, there is still a lack of conclusive evidence due to methodological limitations in the included research. To make trustworthy judgments regarding the efficacy of probiotics in the treatment of RA, more large-scale, high-quality randomized controlled trials are still required. [ABSTRACT FROM AUTHOR]

Progressive loss of retinal ganglionic cells (RGC) causes degeneration of optic nerve axons, which leads to blindness in glaucoma. Elevated intraocular pressure (IOP) is the most important, treatable risk factor. Currently, the management of glaucoma is centred on reducing the IOP, and drugs in the form of topical drops are the first line of management. Drugs reduce IOP either by suppressing aqueous humour secretion or improving the aqueous humour outflow. Newer drugs added during the past three decades to the armamentarium of glaucoma treatment have targeted the aqueous outflow. With an evolving understanding of the pathogenesis of glaucoma, the role of 24-h IOP control and other IOP-independent risk factors affecting ocular blood flow and RGC toxicity is also being actively studied in clinical and pre-clinical models of glaucoma. The role of available drugs in controlling IOP over 24 h is being evaluated. Improvement of ocular blood flow and neuroprotection are seen as potential drug targets for preventing the loss of RGC. In this article, we review the pharmacotherapy of glaucoma based on current therapeutic principles. [ABSTRACT FROM AUTHOR]

Introduction: Periodontitis is a chronic inflammatory disease that leads to the destruction of both the hard and soft tissues of the periodontium. Various herbal extracts can be used as a Local Drug Delivery (LDD) agent to suppress the inflammation caused by micro-organisms. Aim: To evaluate the effectiveness of a hydrogel based on mustard seed extract as an adjunct to Non-surgical Periodontal Therapy (NSPT) for the treatment of chronic periodontitis. Materials and Methods: This pilot interventional study was conducted at Saveetha Dental College and Hospitals, Chennai between June 2023 and July 2023. The study included a total of 30 participants diagnosed with chronic periodontitis who were divided into two groups: group A (n=15) received only Scaling and Root Planing (SRP), while group B (n=15) received SRP along with 0.5% mustard seed extract hydrogel. Baseline and two-week post-operative assessments included recording of Gingival Index (GI), Plaque Index (PI), and modified Sulcus Bleeding Index (mSBI). The data was analysed by Statistical Package for Social Sciences (SPSS), software version 23.0 for windows. An independent t-test was conducted to assess significance between the two groups, while the comparison of baseline and post-operative variables within each group was done using a paired t-test. A p-value of <0.05 was considered statistically significant. Results: The mean age of study participants was 38.04±8.12 years in group A and 40.36±7.45 years in group B. The group treated with 0.5% hydrogel based on mustard seed extract exhibited a noteworthy enhancement in PI (p<0.05*). Intra-group comparisons revealed a significant difference in baseline and 2-week post-operative values for all parameters except mSBI in group A, although group B showed a significant difference for all the parameters (p<0.05*). Inter-group comparisons at two weeks showed statistically significant improvement in group B for PI but not for GI and mSBI. Conclusion: The supplemental application of 0.5% hydrogel derived from mustard seed extract alongside SRP yielded promising outcomes, suggesting a novel approach in the management of chronic periodontitis. [ABSTRACT FROM AUTHOR]

Many individuals with type 1 diabetes (T1D) do not achieve their management goals. The patient perspective on unmet needs in T1D may guide the role of adjunctive therapies, including glucagon like peptide-1 receptor agonists (GLP-1RAs). A quantitative online survey (n = 133) assessed (1) self-reported demographic and management data, (2) management priorities, satisfaction, and willingness to use adjunctive therapies and (3) conducted a risk-benefit analysis using three masked drug profiles (1.8 mg vs 0.6 mg liraglutide vs placebo). A subgroup of respondents (n = 20) participated in semi-structured interviews to extend upon survey insights. Needs were unmet by current treatment in 28% of surveyed individuals. The greatest unmet needs included (1) glycemia, (2) management-related fatigue, and (3) weight management. Most respondents (94%) indicated that they would use adjunctive therapies. The preferred administration route was daily tablets (66%) followed by weekly injections (32%). Metabolic improvements were most valued (reduction in hypoglycemia, hyperglycemia). Most respondents (94%) preferred the liraglutide risk-benefit profile (1.8 mg, then 0.6 mg) over placebo. Individuals with T1D self-report many unmet needs. While not currently approved in T1D, GLP-1RA properties align with many management priorities reported by individuals with T1D. [ABSTRACT FROM AUTHOR]

Breast cancer is associated with high mortality and morbidity rates. As about 20–30% of patients exhibiting ER-positive phenotype are resistant to hormonal treatment with the standard drug tamoxifen, finding new therapies is a necessity. Postbiotics, metabolites, and macromolecules isolated from probiotic bacteria cultures have been proven to have sufficient bioactivity to exert prohealth and anticancer effects, making them viable adjunctive agents for the treatment of various neoplasms, including breast cancer. In the current study, postbiotics derived from L. plantarum and L. rhamnosus cultures were assessed on an in vitro breast cancer model as potential adjunctive agents to therapy utilizing tamoxifen and a candidate aziridine–hydrazide hydrazone derivative drug. Cell viability and cell death processes, including apoptosis, were analyzed for neoplastic MCF-7 cells treated with postbiotics and synthetic compounds. Cell cycle progression and proliferation were analyzed by PI-based flow cytometry and Ki-67 immunostaining. Postbiotics decreased viability and triggered apoptosis in MCF-7, modestly affecting the cell cycle and showing a lack of negative impact on normal cell viability. Moreover, they enhanced the cytotoxic effect of tamoxifen and the new candidate drug toward MCF-7, accelerating apoptosis and the inhibition of proliferation. This illustrates postbiotics' potential as natural adjunctive agents supporting anticancer therapy based on synthetic drugs. [ABSTRACT FROM AUTHOR]

Background: The effect of first-line complex decongestive therapy (CDT) for breast cancer-related lymphedema (BCRL) depending on various factors forces patients to seek additional treatment. Therefore, this meta-analysis was conducted to evaluate the effect of different conservative medical interventions as a complement to CDT. This is the first meta-analysis that includes various kinds of conservative treatments as adjunctive therapy to get broader knowledge and improve practical application value, which can provide recommendations to further improve BCRL patients' health status. Methods: RCTs published before 18 December 2023 from PubMed, Embase, Cochrane Library, and Web of Science databases were searched. RCTs that compared the effects of conservative medical intervention were included. A random-effects or fixed-effects model was used based on the heterogeneity findings. Study quality was evaluated using the Cochrane risk of bias tool. Results: Sixteen RCTs with 690 participants were included, comparing laser therapy, intermittent pneumatic compression (IPC), extracorporeal shock wave therapy (ESWT), electrotherapy, ultrasound, diet or diet in combination with synbiotic supplement, traditional Chinese medicine (TCM), continuous passive motion (CPM), and negative pressure massage treatment (NMPT). The results revealed that conservative medical intervention as complement to CDT had benefits in improving lymphedema in volume/circumference of the upper extremity [SMD = -0.30, 95% CI = (-0.45, -0.15), P < 0.05, I2 = 51%], visual analog score (VAS) for pain [SMD = -3.35, 95% CI (-5.37, -1.33), P < 0.05, I2 = 96%], quality of life [SMD = 0.44, 95% CI (0.19, 0.69), P < 0.05, I2 = 0], and DASH/QuickDASH [SMD = -0.42, 95% CI (-0.70, -0.14), P < 0.05, I2 = 10%] compared with the control group. Subgroup analysis revealed that laser therapy and electrotherapy are especially effective (P < 0.05). Conclusion: Combining conservative medical interventions with CDT appears to have a positive effect on certain BCRL symptoms, especially laser therapy and electrotherapy. It showed a better effect on patients under 60 years old, and laser therapy of low to moderate intensity (5-24 mW, 1.5-2 J/cm2) and of moderateto long-term duration (=36-72 sessions) showed better effects. [ABSTRACT FROM AUTHOR]

• Lacosamide was effective in patients with epilepsy aged 1 month to 4 years. • There were no unexpected safety concerns. • A lower baseline seizure frequency was associated with a higher retention rate. • Younger age group in monotherapy group was associated with a higher retention rate. Lacosamide (LCM) has shown promising efficacy and safety outcomes in clinical trials. However, the evidence is limited among pediatric patients especially under four years in real-world. The study investigated the treatment outcomes and safety of LCM in patients under four years based on the data of the epilepsy registry of Children in China. A prospective cohort study was conducted among patients under 4 years who newly received LCM as monotherapy or adjunctive therapy. The treatment outcomes were measured by retention rate of LCM, 50 % response rates and seizure-free rates during follow-up. The retention rate of LCM was assessed using the Kaplan-Meier survival model. Adverse events were reported as a percentage of all participants. Of 109 participants (mean follow-up: 18.6 months), 59 received LCM as monotherapy and 50 as adjunctive therapy. Sixty patients had focal epilepsy, 44 had generalized epilepsy and 5 had combined generalized and focal epilepsy. 70 % of patients in the monotherapy group and 41 % in the adjunctive therapy group remained on LCM treatment without additional treatments for at least one year. In patients with monotherapy, 50 % response rate and seizure-free rate were 75 % and 56 % at 12 months, respectively. In adjunctive therapy group, these rates were 51 % and 36 %, respectively. Lower baseline seizure frequency in both treatment groups (monotherapy: p < 0.001; adjunctive therapy: p = 0.02) and younger age groups within the monotherapy group (P = 0.04) correlated with a higher LCM retention rate. Adverse events were reported by 15 patients (13.8 %), with somnolence being the most common (7 of 15 patients). With a comprehensive information and high-quality of data, the study demonstrates the effective treatment outcome and safety of LCM. The study adds reliable evidence to exiting real-word evidence of LCM in the specific age group of patients with epilepsy to fill the evidence gap. [ABSTRACT FROM AUTHOR]

Background: to evaluate the effectiveness of different topical agents in biofilm disaggregation during non-surgical periodontal therapy. Methods: the search strategy was conducted according to the PRISMA 2020 on Pubmed, Cochrane Library, Scopus, and Web of Science, and it was registered in PROSPERO, ID: CRD42023474232. It included studies comparing non-surgical periodontal therapy (NSPT) with and without the application of topical agents for biofilm disruption. A risk of bias analysis, a qualitative analysis, and a quantitative analysis were performed. Results: out of 1583 records, 11 articles were included: 10 randomized clinical trials and one retrospective analysis. The total number of participants considered in the 11 articles included in the study was 386. The primary outcomes were probing pocket depth (PPD), clinical attachment level (CAL), and bleeding indices. The secondary outcomes were plaque indices, gingival recessions, and microbiological parameters. The meta-analysis revealed the following: [Weighted mean difference (WMD): −0.37; 95% confidence interval (CI) (−0.62, −0.12), heterogeneity I2: 79%, statistical significance p = 0.004]. Conclusions: the meta-analysis of probing pocket depth reduction (PPD) between baseline and follow-up at 3–6 months showed a statistically significant result in favor of sulfonated phenolics gel. The scientific evidence is still limited and heterogeneous; further randomized clinical trials are required. [ABSTRACT FROM AUTHOR]

Background Because interventions are available to prevent further recurrence in patients with recurrent Clostridioides difficile infection (rCDI), we identified predictors of multiple rCDI (mrCDI) in adults at the time of presentation with initial CDI (iCDI). Methods iCDI was defined as a positive C difficile test in any clinical setting during January 2018–August 2019 in a person aged ≥18 years with no known prior positive test. rCDI was defined as a positive test ≥14 days from the previous positive test within 180 days after iCDI; mrCDI was defined as ≥2 rCDI. We performed multivariable logistic regression analysis. Results Of 18 829 patients with iCDI, 882 (4.7%) had mrCDI; 437 with mrCDI and 7484 without mrCDI had full chart reviews. A higher proportion of patients with mrCDI than without mrCDI were aged ≥65 years (57.2% vs 40.7%; P <.0001) and had healthcare (59.1% vs 46.9%; P <.0001) and antibiotic (77.3% vs 67.3%; P <.0001) exposures in the 12 weeks preceding iCDI. In multivariable analysis, age ≥65 years (adjusted odds ratio [aOR], 1.91; 95% confidence interval [CI], 1.55–2.35), chronic hemodialysis (aOR, 2.28; 95% CI, 1.48–3.51), hospitalization (aOR, 1.64; 95% CI, 1.33–2.01), and nitrofurantoin use (aOR, 1.95; 95% CI, 1.18–3.23) in the 12 weeks preceding iCDI were associated with mrCDI. Conclusions Patients with iCDI who are older, on hemodialysis, or had recent hospitalization or nitrofurantoin use had increased risk of mrCDI and may benefit from early use of adjunctive therapy to prevent mrCDI. If confirmed, these findings could aid in clinical decision making and interventional study designs. [ABSTRACT FROM AUTHOR]

Scaling and root planing (SRP) is the primary treatment for patients with periodontitis. To overcome the limitations of SRP, adjunctive therapy is used to maximise treatment efficacy and optimise patient healing. The effect of adjunctive therapy can be known through biomarker levels before and after treatment. The objective of this research is to determine the effect of adjunctive therapy after initial treatment on MMP-8 levels in periodontitis patients. This scoping review following the Preferred Reporting Items for Systematic Review and MetaAnalysis extension for Scoping Review (PRISMA-ScR) guidelines using PubMed, Google Scholar, Cochrane, Livivo databases, and manual searches. This research was conducted over a period of 6 months. A total of 13 articles were used according to the inclusion criteria. There were 3 articles on antibiotic administration, 1 article on non-steroidal anti-inflammatory drug (NSAID) administration, 2 articles on probiotic administration, 2 articles on herbal administration, 1 article on laser application, 1 article on LED application, 1 article on carbonate apatite mineral administration, 1 article on a comparison of antibiotic administration and licorice herbal administration, and 1 article on a comparison of antibiotic administration and photodynamic therapy as adjunctive therapy. 12 articles showed a significant statistically significant decrease in MMP-8 levels, while 1 article showed a decrease in MMP-8 levels but not statistically significant. Based on the analysis of all articles in this research, adjunctive therapy after initial treatment has an effect on reducing MMP-8 levels in periodontitis patients. [ABSTRACT FROM AUTHOR]

Background: Pulmonary vein isolation (PVI) is the primary technique for ablation of atrial fibrillation (AF). It is unclear whether adjunctive therapies in addition to PVI can reduce atrial arrhythmia recurrence (AAR) compared to PVI alone in patients with AF. Methods: A meta-analysis of randomized controlled trials comparing PVI plus an adjunctive therapy (autonomic modulation, linear ablation, non-pulmonary vein trigger ablation, epicardial PVI [hybrid ablation], or left atrial substrate modification) to PVI alone was conducted. The primary outcome was AAR. Cumulative odd's ratios (OR) and 95% confidence intervals (CI) were calculated for each treatment type. Results: Forty-six trials were identified that included 8,500 participants. The mean age (± standard deviation) was 60.2 (±4.1) years, and 27.2% of all patients were female. The mean follow-up time was 14.6 months. PVI plus autonomic modulation and PVI plus hybrid ablation were associated with a relative 53.1% (OR 0.47; 95% CI 0.32 to 0.69; p < 0.001) and 59.1% (OR 0.41; 95% CI 0.23 to 0.75; p = 0.003) reduction in AAR, respectively, compared to PVI alone. All categories had at least moderate interstudy heterogeneity except for hybrid ablation. Conclusion: Adjunctive autonomic modulation and epicardial PVI may improve the effectiveness of PVI. Larger, multi-center randomized controlled trials are needed to evaluate the efficacy of these therapies. [ABSTRACT FROM AUTHOR]

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Objective: To investigate the in vivo immunomodulatory and anti-tumor mechanisms of the combined treatment of novel Four-Herb formula (4HF) and doxorubicin in triple-negative breast cancer (TNBC). Methods: Murine-derived triple-negative mammary carcinoma cell line, 4T1 cells, was cultured and inoculated into mouse mammary glands. Sixty-six mice were randomly assigned into 6 groups (n=11 in ench): naïve, control, LD 4HF (low dose 4HF), HD 4HF (high dose 4HF), LD 4HF + D (low dose and doxorubicin), and D (doxorubicin). Apart from the naïve group, each mouse received subcutaneous inoculation with 5 × 105 4T1 cells resuspended in 100 µL of normal saline in the mammary fat pads. Starting from the day of tumor cell inoculation, tumors were grown for 6 days. The LD and HD groups received daily oral gavage of 658 and 2,630 mg/kg 4HF, respectively. The LD 4HF+D group received daily oral gavage of 658 mg/kg 4HF and weekly intraperitoneal injection of doxorubicin (5 mg/kg). The D group received weekly intraperitoneal injections of doxorubicin (5 mg/kg). The treatment naïve mice received daily oral gavage of 0.2 mL double distilled water and 0.1 mL normal saline via intraperitoneal injection once a week. The control group received daily oral gavage of 0.2 mL double-distilled water. The treatment period was 30 days. At the end of treatment, mice organs were harvested to analyze immunological activities via immunophenotyping, gene and multiplex analysis, histological staining, and gut microbiota analysis. Results: Mice treated with the combination of 4HF and doxorubicin resulted in significantly reduced tumor and spleen burdens (P<0.05), altered the hypoxia and overall immune lymphocyte landscape, and manipulated gut microbiota to favor the anti-tumor immunological activities. Moreover, immunosuppressive genes, cytokines, and chemokines such as C-C motif chemokine 2 and interleukin-10 of tumors were significantly downregulated (P<0.05). 4HF-doxorubicin combination treatment demonstrated synergetic activities and was most effective in activating the anti-tumor immune response (P<0.05). Conclusion: The above results provide evidence for evaluating the immune regulating mechanisms of 4HF in breast cancer and support its clinical significance in its potential as an adjunctive therapeutic agent or immune supplement. [ABSTRACT FROM AUTHOR]

Background Even on the best antimalarial treatments (injectable artesunate) African children with severe malaria have poor outcomes with most deaths occurring early in the course of hospital admission ( 2mmol/l). Three intravenous doses will be given at admission (0 hours), 8 and 16 hours. APPT will be measured 1 hour after each dose (to assess maximum toxicity). Studying 20 children will allow sufficient data on safety to be generated across a range of doses to identify the maximum tolerated dose (MTD) using the Continual Reassessment Method, which adapts or informs subsequent doses for each child based on the data from previously enrolled children. The MTD will be identified based on the dose-toxicity model updated by each previous patient’s APTT results using standard methods. Conclusions The results of the Phase I trial will identify the final dose to be tested in a Phase II trial in terms of both efficacy and safety outcomes. Registration PACTR number: 202007890194806 (date 20/07/2020) ISRCTN32271864 (date 28/07/2021)

Spasticity and its related symptoms of spasms, pain, sleep disturbance and bladder dysfunction are common in persons with multiple sclerosis (MS) and may be interconnected through a common pathophysiology and/or may trigger and worsen each other. Tetrahydrocannabinol–cannabidiol (nabiximols) oromucosal spray (Sativex) is an add-on treatment for adults with moderate-to-severe MS spasticity who fail to respond adequately to conventional oral medications. There is evidence that nabiximols can ameliorate spasticity-associated symptoms irrespective of its effect on spasticity. This case series describes 12 adults with MS spasticity who were evaluated for symptom evolution before and during adjunctive nabiximols treatment. Nabiximols reduced spasticity severity in 11 patients, of whom 8 had a clinically important ≥30% improvement in 0–10 Numeric Rating Scale scores during treatment. In 7 patients who reported spasms, severity was reduced or spasms were absent/unnoticeable during nabiximols treatment. Walking distance was improved in 8 patients. Pain severity was reduced in 11 patients, and sleep disorder was completely resolved in 3 patients and improved in 8. Bladder dysfunction was improved in 6 of 7 patients with baseline symptoms. Two patients arguably should have discontinued nabiximols sooner: one had a limited response and experienced adverse effects throughout 6 months of treatment; the other was a non-responder who suffered a fall due to dizziness after 7 weeks of use. Overall, this case series shows, at an individual patient level, that the benefits of nabiximols extend beyond spasticity to include spasticity-related symptoms.

Dragana Bugarski-Kirola,1,2 Brandon Abbs,2 Ramzey Odetalla,2 I-Yuan Liu,2 Mona Darwish,2 Daryl DeKarske3 1Acadia Pharmaceuticals GmbH, Basel, Switzerland; 2Acadia Pharmaceuticals Inc, Princeton, NJ, USA; 3Acadia Pharmaceuticals Inc, San Diego, CA, USACorrespondence: Dragana Bugarski-Kirola, Acadia Pharmaceuticals GmbH, Barfüẞerplatz 3, Basel, Switzerland, 4051, Tel +41798658317, Email dbugarski-kirola@acadia-pharm.comBackground: In patients with schizophrenia, study design to optimize adherence and objective measurement of adherence is critical for interpreting results. Two randomized, double-blind studies evaluating adjunctive pimavanserin in patients with schizophrenia who received stable antipsychotic treatment included measures to encourage and assess treatment adherence.Objective: This post hoc analysis evaluated adherence levels achieved in the Phase III ENHANCE study (NCT02970292) and the Phase II ADVANCE study (NCT02970305).Methods: Blood levels of participants receiving adjunctive treatment with pimavanserin or placebo added to their ongoing antipsychotic medication were tested and evaluated regularly throughout both studies. For both the background antipsychotic and pimavanserin, treatment adherence was defined as a blood sample test result above the lower limit of quantification.Results: Overall, 392 of 633 screened patients and 403 of 608 screened patients were in the safety populations in ENHANCE and ADVANCE, respectively. In ENHANCE, at weeks 1, 3, and 6/early termination (ET), the adherence rates remained ≥ 95.1% for the background antipsychotic in both pimavanserin and placebo treatment groups and ≥ 96.8% for pimavanserin. In ADVANCE, high adherence rates (≥ 90.6%) with the background antipsychotic (for both treatment groups) and pimavanserin (≥ 95.0%) were observed at weeks 2, 8, 14, and 26/ET.Conclusion: Rigorous screening was performed to exclude patients not adherent to their background antipsychotic before enrollment and to pimavanserin during study visits by using regular blood sampling. Mandatory caregiver participation further supported adherence to study treatment and procedures. These efforts may have contributed to the high levels of adherence to both background antipsychotic and pimavanserin reported in ENHANCE and ADVANCE.Keywords: adjunctive therapy, treatment compliance, pharmacokinetic drug levels, blood sampling, negative symptoms, caregiver participation

OBJECTIVE: This study aimed to evaluate the efficacy and tolerability of perampanel, which was used in a cohort of patients with refractory epilepsy for up to 3.5 years in a real-world setting in Saudi Arabia. PATIENTS AND METHODS: Data from the medical records of patients treated with perampanel between March 13th, 2017, and September 6th, 2020, at neurology clinics at King Faisal Specialist Hospital and Research Centre (KFSHRC), Riyadh and Jeddah, Saudi Arabia, was collected. The Liverpool Adverse Events Profile (LAEP) scale was also used to measure the adverse effects of perampanel. RESULTS: Of the 75 included patients, 66.7% responded to perampanel at the last follow-up, including 22.7% seizure-free for at least the last six months, and 44% of patients responded with a ≥ 50% reduction in seizure frequency from baseline. The overall incidence of adverse effects that led to perampanel discontinuation was 13.3%; the most common adverse effect was aggressive behavior followed by sedation. Pre-existing psychiatric comorbidity was significantly associated with the incidence of psychiatric and behavioral adverse effects on perampanel (p = 0.0206). The mean score of LEAP was 40. The most frequently rated adverse effects in LEAP were "feelings of anger and aggression to others", "nervousness and/or agitation" and "sleepiness". The efficacy and tolerability of perampanel were dose-dependent. Dose 6 mg/day was the most frequently used dose that was taken by about one-third of patients at their last visit. CONCLUSIONS: Perampanel was effective as an adjunctive treatment for intractable seizures, with a responder rate of 66.7%. The long-term tolerability of perampanel was generally good. Aggressive behavior was the most common reason for perampanel discontinuation. Patients should be counseled and monitored for these adverse effects, particularly those with a history of previous psychiatric and behavioral problems. [ABSTRACT FROM AUTHOR]

Cerebral malaria (CM) is one of the most severe complications of malaria infection characterized by coma and neurological effects. Despite standardized treatment of malaria infection with artemisinin-based combination therapies (ACT), the mortality rate is still high, and it primarily affects pediatric patients. ACT reduces parasitemia but fails to adequately target the pathogenic mechanisms underlying CM, including blood-brain-barrier (BBB) disruption, endothelial activation/dysfunction, and hyperinflammation. The need for adjunctive therapies to specifically treat this form of severe malaria is critical as hundreds of thousands of people continue to die each year from this disease. Here we present a summary of some potential promising therapeutic targets and treatments for CM, as well as some that have been tested and deemed ineffective or, in some cases, even deleterious. Further exploration into these therapeutic agents is warranted to assess the effectiveness of these potential treatments for CM patients. [ABSTRACT FROM AUTHOR]

Aim Acute carpal tunnel syndrome (ACTS) is a well-recognized and common condition following a distal radius fracture. The aim of this study was to test deflazacort associated with Nevridol®800 or deflazacort alone in order to prevent moderate or severe ACTS after the distal radius fracture in adults. Methods Sixty-four patients suffering from extraarticular wrist fractures were divided into three groups. The first group (n=26) was treated by plaster cast. The second group (n=20) was treated by cast and deflazacort (heterocyclic glucocorticoids prodrug belonging to the class of oxazoline steroids) 30 mg/day for 15 days. The third group (n=18) was treated by cast and deflazacort 30 mg/ day for 15 days + Nevridol (food supplements) 800 mg a day for 40 days. The criteria to evaluate the patients were: the complication of ACTS, the duration of symptoms, the functional results were evaluated according to The Disabilities of the Arm, Shoulder and Hand (DASH) life correlated with wrist function by the Short Form 12 Health Survey (SF-12), and positive Tinel and Phalen test. The correlation between ACTS signs and volar tilt in the latero- lateral at X-rays in the three studied groups was assessed. The endpoints were set on 7 days, 15 days, 1 months, 2 months and 3 months after a trauma. Results In the first group, 12 of 26 (46.15%) and the second group 7 of 20 (35%) patients suffered from ACTS, while in the third group only two of 18 (11%) patients (p=0.033). After 3 months of treatment, the third group had better results in DASH (p=0.034), SF-12 (p=0.044), Tinel (0.045) and Phalen (0.048) tests. Conclusion Deflazacort associated with Nevridol 800 may reduce the prevalence of postoperative median nerve dysfunction. [ABSTRACT FROM AUTHOR]

Aims: Inadequate antidepressant response interrupts effective treatment of major depressive disorder (MDD). The BLESS study evaluates the dosage, efficacy, and safety of brexpiprazole adjunctive therapy in Japanese patients with inadequate antidepressant therapy (ADT) response. Methods: This placebo‐controlled, randomized, multicenter, parallel‐group phase 2/3 study randomized Japanese MDD patients (Hamilton Rating Scale for Depression 17‐item total score ≥ 14; historical inadequate response to 1–3 ADTs) with inadequate response to 8‐week single‐blind, prospective SSRI/SNRI treatment to 6‐week adjunctive treatment with brexpiprazole 1 mg, 2 mg, or placebo. The primary endpoint was change in Montgomery‐Åsberg Depression Rating Scale (MADRS) total score from baseline. Secondary endpoints included MADRS response, remission rate, and Clinical Global Impression‐Improvement score. Safety was comprehensively evaluated, especially regarding antipsychotic adverse events (AEs). Results: Of 1194 screened patients, 740 were randomized and 736 (1 mg, n = 248; 2 mg, n = 245; placebo, n = 243) had ≥1 baseline/post‐baseline MADRS total score. The LSM (SE) change from baseline in MADRS total score at Week 6 by MMRM analysis was −8.5 (0.47) with brexpiprazole 1 mg, −8.2 (0.47) with brexpiprazole 2 mg, and −6.7 (0.47) with placebo (placebo‐adjusted LSM difference [95% CI]: 1 mg, −1.7 [−3.0, −0.4]; P = 0.0089; 2 mg, −1.4 [−2.7, −0.1]; P = 0.0312). Secondary efficacy results supported the primary endpoint. Brexpiprazole was generally well tolerated. Conclusion: Brexpiprazole 1 mg daily was an appropriate starting dose and both 1 mg and 2 mg daily were effective and well tolerated as adjunctive therapy for Japanese MDD patients not adequately responsive to ADT. [ABSTRACT FROM AUTHOR]

The current research is designed to investigate the effect of propolis supplementation on the clinical manifestations in women suffering from uncomplicated cystitis. In this randomized double‐blind, placebo‐controlled trial, 120 women with uncomplicated cystitis were selected and randomly assigned into two groups to receive two 500 mg capsules of propolis or placebo daily for 7 days along with ciprofloxacin (250 mg). Clinical symptoms including hematuria, urinary frequency, dysuria, suprapubic pain, and urgency, as well as bacteriuria, were assessed before and after the intervention. After supplementation, participants in the intervention group had significantly fewer days of urinary frequency (p < 0.001), dysuria (p = 0.005), and urgency (p = 0.03). However, there was no significant difference between the two groups regarding hematuria and suprapubic pain (p > 0.05). Furthermore, the severity of bacteriuria decreased significantly in both groups. In conclusion, it seems that propolis supplementation in women with uncomplicated cystitis could improve urinary frequency, dysuria, and urgency. However, further clinical trials should be conducted to fully understand the effects of propolis in women suffering from uncomplicated cystitis. [ABSTRACT FROM AUTHOR]

The aim of this study was to assess the efficacy of acupuncture in the treatment of pressure ulcers. Randomized controlled trials evaluating the effects of acupuncture on pressure ulcers were identified through a comprehensive literature search on public database. The quality assessment of the included trials was performed based on the guidance of the Cochrane Reviewers' Handbook, and pooled analyses were performed by using the RevMan 5.4 software. The pooled results demonstrated that acupuncture in combination with standard wound care was significantly superior to standard wound care alone with regard to effective rate (RR 1.17, 95% CI [1.10, 1.24]), reduction in Wound Size (MD −2.78, 95% CI [−2.43, −1.44]), healing time (MD −6.24, 95% CI [−12.32, −0.17]) and the amount of 24‐h exudate (MD −0.86, 95% CI [−1.54, −0.18]). In conclusion, this study suggests that acupuncture can be used as an adjunctive therapy to promote healing of pressure ulcers. [ABSTRACT FROM AUTHOR]

To systematically appraise the evidence from overlapping systematic reviews/meta‐analyses (SRs/MAs) on electrical stimulation for pressure ulcers. A thorough search of public databases was conducted to collect SRs/MAs on electrical stimulation for pressure ulcers. Two independent authors used the AMSTAR‐2 tool, the PRISMA checklists and the GRADE system to appraise the methodological quality, reporting quality and evidence quality of eligible SRs/MAs. Ten eligible SRs/MAs were included. The methodological quality of two SRs/MAs were determined to be high, six were determined to be very low and two were assessed as being of low quality. For PRISMA checklists, potential factors that undermined the quality of reporting were the lack of reporting on the registration of protocols, search, additional analysis of methodology and additional analysis of results. With GRADE, the evidence quality of two outcomes were determined to be moderate, six were determined to be low and two were assessed as being of very low quality. Electrical stimulation appears to be an adjunctive therapy that may promote the healing of pressure ulcers, but the available evidence suggests caution in recommending electrical stimulation widely for the treatment of pressure ulcers. Large‐scale trials are the focus of future research to find out how electrical stimulation affects all important outcomes. [ABSTRACT FROM AUTHOR]

Background: To assess the efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) used as an adjunct to insulin therapy in adults with type 1 diabetes. Methods: A search of electronic databases (Medline, Embase, and the Cochrane Central Register of Controlled Trials) from 1 January 1950 to 23 May 2021 was conducted to find randomized controlled trials. The primary outcome was the change in HbA1c. Eight efficacy and six safety secondary endpoints were evaluated via meta-analysis. Weighted mean difference (WMD) and odds ratio (OR), alongside 95% confidence interval (CI), were calculated using the random effects model. Results: Among 1,379 candidate studies, 11 trials comprising 2,856 participants satisfied the inclusion criteria. Overall, GLP-1 RA adjunctive therapy reduced HbA1c by -0.21% (95% CI, -0.33 to -0.10), weight by -4.04 kg (-4.8 to -3.27), systolic pressure by -2.57 mmHg (-4.11 to -1.03), and diastolic blood pressure by -1.02 mmHg (-1.99 to -0.06). In addition, there was a decrease in prandial insulin dose (WMD, -4.23 IU; 95% CI, -5.26 to -3.20), basal insulin dose (-2.40 IU; -3.93 to -0.87), and total insulin dose (-5.73 IU; -10.61 to -0.86). Moreover, GLP-1 RAs did not increase the incidence of severe hypoglycemia, diabetic ketoacidosis, or severe adverse events. However, GLP-1 RAs increased the incidence of gastrointestinal adverse events (OR, 2.96; 95% CI, 2.33-3.77). Conclusion: Our meta-analysis of randomized clinical trials suggests moderate beneficial effects of GLP-1 RAs on the metabolic profile in patients with type 1 diabetes, without an increased risk of serious adverse events. Clinical Trial Registration: https://www.crd.york.ac.uk/PROSPERO; Identifier: CRD 42020199840. [ABSTRACT FROM AUTHOR]

Problem: Hyperkalemia is a serious condition among intra‐abdominal transplant recipients, and the safety and efficacy of sodium zirconium cyclosilicate (SZC) for its management during the early post‐transplant period are not well‐established. Methods: Adults who received at least one 10‐g dose of SZC within 14 days after an intra‐abdominal transplant between January 2020 and July 2022 were included in our study. The primary outcome was the change in potassium (K+) levels following the first SZC dose. Other analyses explored adjunctive potassium‐lowering therapies, potential gastrointestinal complications, and patient subgroups based on therapy and transplant type. Results: Among the recipients (n = 46), 11 were kidney recipients, 26 were liver recipients, seven were simultaneous liver/kidney recipients, and two were simultaneous pancreas/kidney recipients. The mean time to first dose post‐transplant was 7.6 (±4) days, and the mean change in serum K+ after the initial SZC dose was −.27 mEq (p =.001). No gastrointestinal complications were observed following the SZC dose. The mean increase in serum bicarbonate was.58 mEq (p =.41) following the first dose of SZC. Four kidney recipients required dialysis following the SZC dose. Conclusion: This study represents the largest investigation on the use of SZC in transplant recipients. A single 10‐g dose of SZC reduced serum K+ levels in all subgroups, while the use of adjunctive K+‐lowering therapies did not provide additional reduction beyond the effects of SZC. Importantly, no gastrointestinal complications were observed. These findings suggest that SZC may be a safe and promising therapeutic option for hyperkalemia management following solid organ transplantation. [ABSTRACT FROM AUTHOR]

Abstract Objective To investigate the therapeutic efficacy of total flavonoids of Rhizoma Drynariae (TFRD) in conjunction with a calcium phosphate/collagen scaffold for the repair of cranial defects in rats. Methods The subjects, rats, were segregated into four groups: Control, TFRD, Scaffold, and TFRD + Scaffold. Cranial critical bone defects, 5 mm in diameter, were artificially induced through precise drilling. Post-surgery, at intervals of 2, 4, and 8 weeks, micro-CT scans were conducted to evaluate the progress of skull repair. Hematoxylin–eosin and Masson staining techniques were applied to discern morphological disparities, and immunohistochemical staining was utilized to ascertain the expression levels of local osteogenic active factors, such as bone morphogenetic protein 2 (BMP-2) and osteocalcin (OCN). Results Upon examination at the 8-week mark, cranial defects in the Scaffold and TFRD + Scaffold cohorts manifested significant repair, with the latter group displaying only negligible foramina. Micro-CT examination unveiled relative to its counterparts, and the TFRD + Scaffold groups exhibited marked bone regeneration at the 4- and 8-week intervals. Notably, the TFRD + Scaffold group exhibited substantial bone defect repair compared to the TFRD and Scaffold groups throughout the entire observation period, while histomorphological assessment demonstrated a significantly higher collagen fiber content than the other groups after 2 weeks. Immunohistochemical analysis further substantiated that the TFRD + Scaffold had augmented expression of BMP-2 at 2, 4 weeks and OCN at 2 weeks relative to other groups. Conclusions The synergistic application of TFRD and calcium phosphate/collagen scaffold has been shown to enhance bone mineralization, bone plasticity, and bone histomorphology especially during initial osteogenesis phases.

Background: Lumbar spinal fusion surgeries are increasing steadily due to an aging and ever-growing population. Patients undergoing lumbar spinal fusion surgery may present with risk factors that contribute to complications, pseudarthrosis, prolonged pain, and reduced quality of life. Pulsed electromagnetic field (PEMF) stimulation represents an adjunct noninvasive treatment intervention that has been shown to improve successful fusion and patient outcomes following spinal surgery. Methods: A prospective, multicenter study investigated PEMF as an adjunct therapy to lumbar spinal fusion procedures in patients at risk for pseudarthrosis. Patients with at least 1 of the following risk factors were enrolled: prior failed fusion, multilevel fusion, nicotine use, osteoporosis, or diabetes. Fusion status was determined by radiographic imaging, and patient-reported outcomes were also evaluated. Results: A total of 142 patients were included in the analysis. Fusion status was assessed at 12 months follow-up where 88.0% (n = 125/142) of patients demonstrated successful fusion. Fusion success for patients with 1, 2+, or 3+ risk factors was 88.5%, 87.5%, and 82.3%, respectively. Significant improvements in patient-reported outcomes using the Short Form 36, EuroQol 5 Dimension (EQ-5D) survey, Oswestry Disability Index, and visual analog scale for back and leg pain were also observed compared with baseline scores (P < 0.001). A favorable safety profile was observed. PEMF treatment showed a positive benefit-risk profile throughout the 6-month required use period. Conclusions: The addition of PEMF as an adjunct treatment in patients undergoing lumbar spinal surgery provided a high rate of successful fusion with significant improvements in pain, function, and quality of life, despite having risk factors for pseudarthrosis. Clinical Relevance: PEMF represents a useful tool for adjunct treatment in patients who have undergone lumbar spinal surgery. Treatment with PEMF may result in improved fusion and patient-reported outcomes, regardless of risk factors. [ABSTRACT FROM AUTHOR]

Ischemic stroke presents a major global economic and public health burden. Although recent advances in available endovascular therapies show improved functional outcome, a good number of stroke patients are either ineligible or do not have access to these treatments. Also, robust collateral flow during acute ischemic stroke independently predicts the success of endovascular therapies and the outcome of stroke. Hence, adjunctive therapies for cerebral blood flow (CBF) enhancement are urgently needed. A very clear overview of the pial collaterals and the role of genetics are presented in this review. We review available evidence and advancement for potential therapies aimed at improving CBF during acute ischemic stroke. We identified heme-free soluble guanylate cyclase activators; Sanguinate, remote ischemic perconditioning; Fasudil, S1P agonists; and stimulation of the sphenopalatine ganglion as promising potential CBF-enhancing therapeutics requiring further investigation. Additionally, we outline and discuss the critical steps required to advance research strategies for clinically translatable CBF-enhancing agents in the context of acute ischemic stroke models. [ABSTRACT FROM AUTHOR]

Objective: To investigate the therapeutic efficacy of total flavonoids of Rhizoma Drynariae (TFRD) in conjunction with a calcium phosphate/collagen scaffold for the repair of cranial defects in rats. Methods: The subjects, rats, were segregated into four groups: Control, TFRD, Scaffold, and TFRD + Scaffold. Cranial critical bone defects, 5 mm in diameter, were artificially induced through precise drilling. Post-surgery, at intervals of 2, 4, and 8 weeks, micro-CT scans were conducted to evaluate the progress of skull repair. Hematoxylin–eosin and Masson staining techniques were applied to discern morphological disparities, and immunohistochemical staining was utilized to ascertain the expression levels of local osteogenic active factors, such as bone morphogenetic protein 2 (BMP-2) and osteocalcin (OCN). Results: Upon examination at the 8-week mark, cranial defects in the Scaffold and TFRD + Scaffold cohorts manifested significant repair, with the latter group displaying only negligible foramina. Micro-CT examination unveiled relative to its counterparts, and the TFRD + Scaffold groups exhibited marked bone regeneration at the 4- and 8-week intervals. Notably, the TFRD + Scaffold group exhibited substantial bone defect repair compared to the TFRD and Scaffold groups throughout the entire observation period, while histomorphological assessment demonstrated a significantly higher collagen fiber content than the other groups after 2 weeks. Immunohistochemical analysis further substantiated that the TFRD + Scaffold had augmented expression of BMP-2 at 2, 4 weeks and OCN at 2 weeks relative to other groups. Conclusions: The synergistic application of TFRD and calcium phosphate/collagen scaffold has been shown to enhance bone mineralization, bone plasticity, and bone histomorphology especially during initial osteogenesis phases. [ABSTRACT FROM AUTHOR]

Chronic obstructive pulmonary disease (COPD), which has a high prevalence and mortality rate, is an irreversible condition marked by airflow restriction with different degrees of reversible damage. Notably, there is no cure for COPD, whose treatment primarily relies on rehabilitation exercises to improve airflow limitation. In this paper, a vision-based rehabilitation exercise efficacy prediction system is proposed to assess the efficacy of rehabilitation training for COPD patients. A camera was utilized to capture rehabilitation training videos of COPD patients, and we also collected various physical indicators. In addition, we used clustering algorithm to divide patients with different rehabilitation effects for subsequent progression analysis. Our model achieved a classification of rehabilitation progress accuracy of 90.6%, making it possible to effectively obtain favorable rehabilitation training results without physician supervision. It was meaningful for helping COPD patients get effective feedback when training alone. [ABSTRACT FROM AUTHOR]

Background Steroids have pleiotropic neuroprotective actions including the regulation of inflammation and apoptosis which may influence the effects of ischemia on neurons, glial cells, and blood vessels. The effect of low‐dose methylprednisolone in patients with acute ischemic stroke in the endovascular therapy era remains unknown. This trial investigates the efficacy and safety of low‐dose methylprednisolone (2 mg/kg IV for 3 days) as adjunctive therapy for patients with acute ischemic stroke undergoing endovascular therapy within 24 hours from symptom onset. Methods The MARVEL (Methylprednisolone as Adjunctive Therapy for Acute Large Vessel Occlusion: A Randomized Double‐Blind, Placebo‐Controlled Trial in Patients Undergoing Endovascular Therapy) trial is an investigator‐initiated, prospective, randomized, double‐blind, placebo‐controlled multicenter clinical trial. Up to 1672 eligible patients with anterior circulation large‐vessel occlusion stroke presenting within 24 hours from symptom onset are planned to be consecutively randomized to receive methylprednisolone or placebo in a 1:1 ratio across 82 stroke centers in China. Results The primary outcome is the ordinal shift in the modified Rankin scale score at 90 days. Secondary outcomes include 90‐day functional independence (modified Rankin scale score, 0–2). The primary safety end points include mortality rate at 90 days and symptomatic intracerebral hemorrhage within 48 hours of endovascular therapy. Conclusion The MARVEL trial will provide evidence of the efficacy and safety of low‐dose methylprednisolone as adjunctive therapy for patients with anterior circulation large‐vessel occlusion stroke undergoing endovascular therapy.

Cerebral malaria (CM) is one of the most severe complications of malaria infection characterized by coma and neurological effects. Despite standardized treatment of malaria infection with artemisinin-based combination therapies (ACT), the mortality rate is still high, and it primarily affects pediatric patients. ACT reduces parasitemia but fails to adequately target the pathogenic mechanisms underlying CM, including blood-brain-barrier (BBB) disruption, endothelial activation/dysfunction, and hyperinflammation. The need for adjunctive therapies to specifically treat this form of severe malaria is critical as hundreds of thousands of people continue to die each year from this disease. Here we present a summary of some potential promising therapeutic targets and treatments for CM, as well as some that have been tested and deemed ineffective or, in some cases, even deleterious. Further exploration into these therapeutic agents is warranted to assess the effectiveness of these potential treatments for CM patients.

Given that the disease progression of tuberculosis (TB) is primarily related to the host’s immune status, it has been gradually realized that chemotherapy that targets the bacteria may never, on its own, wholly eradicate Mycobacterium tuberculosis, the causative agent of TB. The concept of host-directed therapy (HDT) with immune adjuvants has emerged. HDT could potentially interfere with infection and colonization by the pathogens, enhance the protective immune responses of hosts, suppress the overwhelming inflammatory responses, and help to attain a state of homeostasis that favors treatment efficacy. However, the HDT drugs currently being assessed in combination with anti-TB chemotherapy still face the dilemmas arising from side effects and high costs. Natural products are well suited to compensate for these shortcomings by having gentle modulatory effects on the host immune responses with less immunopathological damage at a lower cost. In this review, we first summarize the profiles of anti-TB immunology and the characteristics of HDT. Then, we focus on the rationale and challenges of developing and implementing natural products-based HDT. A succinct report of the medications currently being evaluated in clinical trials and preclinical studies is provided. This review aims to promote target-based screening and accelerate novel TB drug discovery.

Abstract Background The current review broadly summarises the evidence base for pharmacotherapies and adjunctive and alternative therapies in the treatment of eating disorders and disordered eating. Methods This paper forms part of a Rapid Review series examining the evidence base in the field of eating disorders. This was conducted to inform the Australian National Eating Disorder Research and Translation Strategy 2021–2030. ScienceDirect, PubMed and Ovid/Medline were searched for included studies published between 2009 and 2021 in English. High-level evidence such as meta-analyses, large population studies and randomised control trials were prioritised, and grey literature excluded. Data from included studies relating to pharmacotherapy, and to adjunctive and alternative therapies in eating disorders, were synthesised and disseminated in the current review. Results A total of 121 studies were identified, relating to pharmacotherapy (n = 90), adjunctive therapies (n = 21) and alternative therapies (n = 22). Some of the identified studies involved combinations of the above (e.g. adjunctive pharmacotherapy). Evidence of efficacy of interventions across all three categories was very limited with few relevant high quality clinical trials. There was a particular scarcity of evidence around effective treatments for anorexia nervosa (AN). With treatment of bulimia nervosa (BN), fluoxetine has exhibited some efficacy leading to regulatory approval in some countries. With binge eating disorder (BED), recent evidence supports the use of lisdexamfetamine. Neurostimulation interventions show some emerging efficacy in the treatment of AN, BN and BED but some, such as deep brain stimulation can be highly invasive. Conclusion Despite widespread use of medications, this Rapid Review has identified a lack of effective medications and adjunctive and alternative therapies in the treatment of EDs. An intensification of high-quality clinical trial activity and drug discovery innovation are required to better assist patients suffering from EDs.

Closed-loop insulin delivery systems are fast becoming the standard of care in the management of type 1 diabetes and have led to significant improvements in diabetes management. Nevertheless, there is still room for improvement for the closed-loop systems to optimize treatment and meet target glycemic control. Adjunct treatments have been introduced as an alternative method to insulin-only treatment methods to overcome diabetes treatment challenges and improve clinical and patient reported outcomes during closed-loop treatment. The adjunct treatment agents mostly consist of medications that are already approved for type 2 diabetes treatment and aim to complete the missing physiologic factors, such as the entero-endocrine system, that regulate glycemia in addition to insulin. This paper will review many of these adjunct therapies, including the basic mechanisms of action, potential benefits, side effects, and the evidence supporting their use during closed-loop treatment.

Background: to evaluate the effectiveness of different topical agents in biofilm disaggregation during non-surgical periodontal therapy. Methods: the search strategy was conducted according to the PRISMA 2020 on Pubmed, Cochrane Library, Scopus, and Web of Science, and it was registered in PROSPERO, ID: CRD42023474232. It included studies comparing non-surgical periodontal therapy (NSPT) with and without the application of topical agents for biofilm disruption. A risk of bias analysis, a qualitative analysis, and a quantitative analysis were performed. Results: out of 1583 records, 11 articles were included: 10 randomized clinical trials and one retrospective analysis. The total number of participants considered in the 11 articles included in the study was 386. The primary outcomes were probing pocket depth (PPD), clinical attachment level (CAL), and bleeding indices. The secondary outcomes were plaque indices, gingival recessions, and microbiological parameters. The meta-analysis revealed the following: [Weighted mean difference (WMD): −0.37; 95% confidence interval (CI) (−0.62, −0.12), heterogeneity I2: 79%, statistical significance p = 0.004]. Conclusions: the meta-analysis of probing pocket depth reduction (PPD) between baseline and follow-up at 3–6 months showed a statistically significant result in favor of sulfonated phenolics gel. The scientific evidence is still limited and heterogeneous; further randomized clinical trials are required.

Ajeng Diantini,1,&ast; R Maya Febriyanti,2,&ast; Jutti Levita1,&ast; 1Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Padjadjaran University, Sumedang, West Java, 46363, Indonesia; 2Department of Biology Pharmacy, Faculty of Pharmacy, Padjadjaran University, Sumedang, West Java, 46363, Indonesia&ast;These authors contributed equally to this workCorrespondence: Jutti Levita, Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Padjadjaran University, Sumedang, West Java, 46363, Indonesia, Tel +6222-84288888 Ext 3510, Email jutti.levita@unpad.ac.idAbstract: COVID‐19 caused by the infection of SARS‐CoV‐2 is still a global concern. WHO reported that from 13 March to 9 April 2023, there were 3 million new cases and approximately 23,000 deaths, mostly occurring in the South-East Asia and Eastern Mediterranean regions, which is predicted due to the new Omicron variant, Arcturus XBB.1.16. Many studies have reported the potency of medicinal plants in enhancing the function of the immune system to combat virus infection. The literature review aimed to describe the efficacy and safety of add-on plant-based drugs for COVID-19 patients. The articles were explored on the PubMed and Cochrane Library databases, and published during 2020– 2023. Twenty-two varieties of plants were used as add-on therapy for COVID-19 patients. These plants were Andrographis paniculata, Viola odorata, Withania somnifera, Zingiber officinale, Curcuma longa, Ferula foetida, Centella asiatica, Thymus vulgaris, Citrus sinensis, Eugenia caryophyllus, Boswellia carterii, Elettaria cardamomum, Salvia rosmarinus, Piper nigrum, Alstonia scholaris, Picrorhiza kurroa, Swertia chirata, Caesalpinia crista, Cucurbita maxima, Tinospora cordifolia, Ocimum sanctum, and Allium sativum. The best efficacy of an add-on therapy for COVID-19 patients was found in A. paniculata herbs as a single component in pharmaceutical dosage form or in combination with other plants. The safety of the plant has been confirmed. A. paniculata does not show interaction with remdesivir or favipiravir, however, caution and therapy drug monitoring is needed if A. paniculata is used in combination with lopinavir or ritonavir because a strong noncompetitive inhibition of CYP3A4 may occur.Keywords: adjunctive therapy, flavonoids, plant-based therapy, immunomodulatory activity, clinical studies

Nikita Naicker,1 Hylton Rodel,2 Rubeshan Perumal,1 Yashica Ganga,2 Mallory Bernstein,2 Ntombi Benede,2 Salim Abdool Karim,1,3 Nesri Padayacthi,1,3 Alex Sigal,2,4,5 Kogieleum Naidoo1,3 1Centre for the AIDS Programme of Research in South Africa (CAPRISA), Durban, South Africa; 2Africa Health Research Institute, Durban, South Africa; 3MRC-CAPRISA HIV-TB Pathogenesis and Treatment Research Unit, Doris Duke Medical Research Institute; University of KwaZulu-Natal, Durban, South Africa; 4School of Laboratory Medicine and Medical Sciences; University of KwaZulu-Natal, Durban, South Africa; 5Max Planck Institute for Infection Biology, Berlin, GermanyCorrespondence: Nikita Naicker, Doris Duke Medical Research Institute, 2nd Floor, 719 Umbilo Road, Durban, 4041, South Africa, Tel +27843011636, Email nikita.naicker@caprisa.orgIntroduction: Current TB treatment regimens are pathogen-directed and can be severely compromised by the development of drug resistance. Metformin has been proposed as an adjunctive therapy for TB, however relatively little is known about how metformin modulates the cellular interaction between Mtb and macrophages. We aimed to characterize how metformin modulates Mtb growth within macrophages.Methods: We utilized live cell tracking through time-lapse microscopy to better understand the biological effect of metformin in response to Mtb infection. Furthermore, the potent first-line anti-TB drug, isoniazid, was used as a comparator and as a companion drug.Results: Metformin caused a 14.2-fold decrease in Mtb growth compared to the untreated control. Metformin combined with isoniazid controlled Mtb growth is slightly better than isoniazid alone. Metformin demonstrated the ability to regulate the cytokine and chemokine response over a 72 hour period, better than isoniazid only.Conclusion: We provide novel evidence that metformin controls mycobacterial growth by increasing host cell viability, and a direct and independent pro-inflammatory response to Mtb. Understanding the impact of metformin on Mtb growth within macrophages will advance our current knowledge on metformin as an adjunctive therapy, providing a new host-directed approach to TB treatment.Keywords: metformin, tuberculosis, host-directed therapy, INH, adjunctive therapy

IntroductionPharmacological treatment may be effective for treating positive symptoms of schizophrenia; no evidence of clinically significant effects on negative and cognitive symptoms, social and behavioral functioning. This review investigated treatment outcomes of multiple (at least four sessions in 4 weeks) group music therapy sessions adjunct to standard care in inpatients with chronic schizophrenia.MethodsA systematic review search of five electronic medical and psychological databases conducted using keywords “music therapy” and “schizophrenia” up to December 2021. Screening was performed for published articles on any adjunct multiple group music therapy (four sessions in 4 weeks minimum) adjunct to “treatment as usual” for inpatients with “chronic” schizophrenia. All study outcomes were all included. Risk of bias of all studies was assessed.Results1160 articles were screened, and 13 randomized controlled trials (RCTs) with a total of 1,114 inpatients were included. Ten RCTs reported open group sessions with active structured music making (ASMM) combining passive music listening (PML) and/or active singing, playing instruments, and improvisations while three other studies applied PML only. Four studies reported significant outcomes for both positive and negative symptoms. Ten of the thirteen studies recorded significant improvements in negative symptoms, behavioral and social functioning. Lasting significant effects were found in a longitudinal RCT with 272 samples evaluated unguided pre-recorded PML as a coping method lasting up to six months and similar results found in another two longitudinal RCTs. Secondary outcomes measured cognition, mood, social interest and function, self-care ability, interpersonal relationships, and QoL all showed significant outcomes. The significance level for pre-post intervention and between-group measures ranged from p

To report the long-term efficacy of adjunctive lacosamide therapy in patients with juvenile myoclonic epilepsy whose generalized tonic-clonic seizures were significantly reduced by treatment. A retrospective study was conducted in patients who visited the Department of Child Neurology, National Hospital Organization Nishiniigata Chuo Hospital and the Department of Pediatrics, National Hospital Organization Nagasaki Medical Center. Among patients who had been diagnosed with juvenile myoclonic epilepsy, those who received lacosamide as adjunctive therapy for refractory generalized tonic-clonic seizures for at least 2 years from January 2017 to December 2022, and who achieved seizure freedom or >50% seizure reduction in tonic-clonic seizures were included. The medical records and neurophysiological data of the patients were reviewed retrospectively. Four patients met the inclusion criteria. The mean age at the onset of epilepsy was 11.3 years (range 10–12), and the mean age of starting lacosamide was 17.5 years (range 16–21). All patients received two or more antiseizure medications prior to lacosamide. Three of four patients had seizure freedom for more than 2 years, and the one remaining patient had >50% seizure reduction for more than one year. Only one patient had recurrent myoclonic seizures after starting lacosamide. The mean lacosamide dose at the last visit was 425 mg/day (range 300–600). Adjunctive lacosamide therapy might be a treatment option for juvenile myoclonic epilepsy with generalized tonic-clonic seizures, which are not responsive to standard antiseizure medications. [ABSTRACT FROM AUTHOR]