Significant Difference In Efficacy Research Articles

Retrospective Analysis of Once-Daily Versus Twice-Daily Insulin Glargine Dosing in Noncritically Ill Individuals.

Insulin is the treatment of choice for diabetes care in the hospital. There is some debate regarding the efficacy and safety of once-daily versus twice-daily insulin glargine in the hospital, particularly in the critically ill population. The purpose of this pilot study was to evaluate the efficacy and safety of insulin glargine administered as a once-daily versus twice-daily regimen in the noncritically ill population. A retrospective chart review was conducted from 1 June 2020 to 31 May 2021. Inclusion criteria were age ≥18 years and on a regimen of either once-daily or twice-daily insulin glargine for ≥72 hours during the specified time frame. The primary end point was a comparison of the number of days with all blood glucose measurements within the range of 70-180 mg/dL throughout a 24-hour period. Secondary end points included the number of hyperglycemic (>180 mg/dL) and hypoglycemic (<70 mg/dL) events that occurred in each study group. Group 1 included 101 individuals who received once-daily dosing, and group 2 included 103 individuals who received twice-daily dosing. Baseline characteristics were similar between the groups except for a higher BMI at admission (P = 0.01) and a higher pre-admission A1C (P = 0.02) in group 2. No differences were found for the primary end point (P = 0.5) or for hypoglycemic (P = 0.6) or hyperglycemic (P = 0.7) events. There were no significant differences in efficacy or safety between once-daily and twice-daily insulin glargine in the noncritically ill population. A larger prospective study could confirm these results.

Construction and validation of a colon cancer prognostic model based on tumor mutation burden-related genes

Currently, immunotherapy has entered the clinical diagnosis and treatment guidelines for colon cancer, but existing immunotherapy markers cannot predict the effectiveness of immunotherapy well. This study utilized the TCGA-COAD queue to perform differential gene analysis on high and low-mutation burden samples, and screen differentially expressed genes (DEGs). To explore new molecular markers or predictive models of immunotherapy by using DEGs for NMF classification and prognostic model construction. Through systematic bioinformatics analysis, the TCGA-COAD cohort was successfully divided into high mutation burden subtypes and low mutation burden subtypes by NMF typing using DEGs. The proportion of MSI-H between high mutation burden subtypes was significantly higher than that of low mutation burden subtypes, but there was no significant difference in immunotherapy efficacy between the two subtypes. Drug sensitivity analysis showed significant differences in drug sensitivity between the two subtypes. Subsequently, we constructed a prognostic model using DEGs, which can effectively predict patient survival and immunotherapy outcomes. The prognosis and immunotherapy outcomes of the low-risk group were significantly better than those of the high-risk group. The external dataset validation of the constructed prognostic model using the GSE39582 dataset from the GEO database yielded consistent results. At the same time, we also analyzed the TMB and MSI situation between the high and low-risk groups, and the results showed that there was no significant difference in TMB between the high and low-risk groups, but the proportion of MSI-H in the high-risk group was significantly higher than that in the low-risk group. Finally, we conclude that TMB is not a suitable molecular marker for predicting the efficacy of immunotherapy in colon cancer. The newly constructed prognostic model can effectively differentiate the prognosis of colon cancer patients and predict their immunotherapy efficacy.

Outcomes of 3-year follow up with induction vs first line chemotherapy in oral cancer patients: An observational hospital-based study.

Our study aims to analyse and compare the efficacy, adverse effect profile and survival among the Paclitaxel/Cisplatin/5-Flurouracil (TPF) induction chemotherapy and Paclitaxel/carboplatin (PC) first line or cisplatin chemotherapy in a high-volume tertiary care cancer centre. 215 patients with oral cavity cancer were recruited in this study. Patients with stages I-IIc underwent surgical resection or radiation therapy 66-74 GY/fraction. Patients of Stages III-IV were administered with either induction chemotherapy TPF or PC or cisplatin regimen. Treatment responses were assessed by CT and MRI. Response rates, survival and adverse effects data were tabulated and analysed. The mean age was 49.2 ± 11.68 years. Symptoms were ulceration (33.5%), growth (20.5%), pain (13%), ulcer-proliferative growth (8.4%) and swelling (13, 6%). The tumour site was found at the base of the tongue, C01 (42.2%) followed by C06 (35.8%), C08 (6.5%), C07 (5.2%) and C05 (4.6%). There were no significant differences ( P > 0.05) in efficacy and survival outcomes between the different groups of treatment. Median survival was achieved within 36 months. The major side effect observed were anaemia (15.81%), diarrhoea (36.2%), dyspepsia (28.8%), fever (33.95%), mucositis (28.85%), myalgia (33.95%) and nausea (7.9%). Survival among the responder categories (CR, PR and NR) was significantly different as per Log-rank analysis ( P = 0.015). TPF induction therapy and PC first line chemotherapy showed similar efficacy, safety profile and survival whereas cisplatin shows poor efficacy and safety and survival in Indian oral cancer patients.

Comparison of Combined Parenteral and Oral Hormonal Contraceptives: A Systematic Review and Meta-Analysis of Randomized Trials.

Delivering contraceptive hormones through a transdermal patch or a vaginal ring might have advantages over the traditional oral route. To compare the effectiveness, compliance, and side effect profile of oral and parenteral drug administration methods. We performed a systematic literature search in four medical databases-MEDLINE (via PubMed), Cochrane Library (CENTRAL), Embase, and Scopus-from inception to 20 November 2022. Randomized controlled trials assessing the efficacy, compliance, and adverse event profile of combined parenteral and oral hormonal contraceptives were included. Our systematic search provided 3952 records; after duplicate removal, we screened 2707 duplicate-free records. A total of 13 eligible studies were identified after title, abstract, and full-text selection. We observed no significant difference in contraceptive efficacy (Pearl Index) between oral and parenteral drug administration (MD = -0.06, CI: -0.66-0.53; I2 = 0%). We found significant subgroup differences between parenteral methods in terms of compliance (χ2 = 4.32, p =0.038, I2 = 80%) and certain adverse events: breast discomfort (χ2 = 19.04, p =0.001, I2 = 80%), nausea (χ2 = 8.04, p =0.005, I2 = 75%), and vomiting (χ2 = 9.30, p =0.002; I2 = 72%). Both parenteral and oral contraceptives can be used as an effective contraceptive method, and the route of administration should be tailored to patient needs and adverse event occurrence.

Lung adenocarcinoma with brain metastasis detected dual fusion of LOC399815-ALK and ALK-EML4 in combined treatment of Alectinib and CyberKnife: A case report.

The anaplastic lymphoma kinase (ALK) gene fusion occurs in approximately 3% to 7% of nonsmall cell lung cancer (NSCLC), in which occurs approximately 23% to 31% of brain metastasis patients in poor prognosis. ALK tyrosine kinase inhibitors have shown efficacy in treating ALK-positive (ALK+) NSCLC. More than 90 distinct subtypes of ALK fusions have been identified through sequencing technique and would lead to significant differences in clinical efficacy, it is necessary to guide clinical treatment effectively by gene detection. A 56-year-old nonsmoking female admitted to hospital due to cough, expectoration, and chest pain. Chest computed tomography revealed a space-occupying lesion in the upper left lobe (5.0 cm × 2.4 cm × 2.9 cm), multiple enlarged lymph nodes in mediastinum 3A and 5 (largest size 1.5 cm × 1.4 cm), and evidence of thoracic vertebral metastasis, brain magnetic resonance imaging also showed brain metastasis. Lung adenocarcinoma with brain metastasis. The patient initially received conventional first-line chemotherapy, which led to a deteriorated condition. Blood-base liquid biopsy by next-generation sequencing resulted in double ALK fusions, in which with a neo-partner of lncRNA (LOC399815-ALK). Following subsequent treatment with Alectinib and stereotactic radiotherapy (CyberKnife) was subsequently employed to manage the brain metastatic lesions, resulting in a substantial decreased in both the number and size of tumor lesions. The patient's response to therapy efficacy resulted in a substantial decreased in both the number and size of tumor lesions that assessed comprehensively evaluated through computed tomography imaging and ctDNA sequencing. Patient's condition has been under control for over 29 months. Liquid biopsy may reveal the rare fusion forms of ALK, precisely guiding personalized treatment, and providing a reference method for longitudinal monitoring and efficacy evaluation of ALK-tyrosine kinase inhibitors in NSCLC patients.

Effectiveness and safety of robot-assisted minimally invasive transforaminal lumbar interbody fusion for degenerative lumbar spinal diseases: a systematic review and meta-analysis.

Robot-assisted (RA) technology has been widely used in spine surgery. This analysis aimed to compare the effectiveness and safety of RA minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) and fluoroscopy-assisted (FA) MIS-TLIF for degenerative lumbar spinal diseases (DLSD). PubMed, Web of Science, Cochrane Library, and China National Knowledge Infrastructure were systematically searched, and the outcomes included surgical parameters [operation time, blood loss, number of fluoroscopic, accuracy of pedicle screw position, superior facet joint violation (FJV)], and clinical indexes (Visual Analog Scale (VAS), Oswestry Disability Index (ODI), Japanese Orthopaedic Association (JOA) score, clinical efficacy, hospital stays, complications). Eleven articles involving 1066 patients were included. RA group produced better results than the FA group in operation time (WMD = -6.59; 95% CI -12.79 to -0.40; P = 0.04), blood loss (WMD = -34.81; 95% CI -50.55 to -19.08; P < 0.0001), number of fluoroscopic (WMD = -18.24; 95% CI -30.63 to -5.85; P = 0.004), accuracy of pedicle screw position: Grade A (OR = 3.16; 95% CI 2.36-4.23; P < 0.00001), Grade B (OR = 0.39; 95% CI 0.28-0.54; P < 0.00001), Grade C (OR = 0.27; 95% CI 0.13-0.54; P = 0.0002), and Grade D (OR = 0.17; 95% CI 0.03-0.98; P = 0.05), FJV: Grade 0 (OR = 3.27; 95% CI 1.34-8.02; P = 0.010), Grade 1 (OR = 0.24; 95% CI 0.16-0.38; P < 0.00001), Grade 2 (OR = 0.24; 95% CI 0.12-0.51; P = 0.0002), and Grade 3 (OR = 0.26; 95% CI 0.07-0.93; P = 0.04). But no significant differences in VAS score, ODI, JOA score, clinical efficacy, hospital stays, and complications. These results demonstrate a significant improvement in the intraoperative course of the RA technique. However, RA-MIS-TLIF has not yet demonstrated significant advantages in terms of postoperative symptom relief and functional improvement. Future research and clinical practice should further explore the efficacy of this technique to optimize outcomes and quality of life for patients with DLSD. The study was registered in the PROSPERO (CRD42023454405).

Efficacy and safety of perampanel as the first add-on therapy for children with epilepsy: A real-world multicenter prospective observational study

ObjectivePerampanel (PER) is a new anti-seizure medication (ASM) with a novel mechanism of action. This study aimed to determine the efficacy and safety of PER when added to monotherapy in children and adolescents (age, 4–18 years) with epilepsy. MethodA multicenter prospective observational study was performed on children and adolescents (age, 4–18 years) with epilepsy who did not respond to ASM monotherapy between July 2021 and October 2022. PER was used as the first add-on therapy for the enrolled patients. Seizure-free rate, response rate, inefficacy rate, and drug retention rate were the main observation indicators during the 6 months of treatment. The patients were grouped based on treatment efficacy, and factors affecting efficacy were statistically analyzed. Adverse reactions were also recorded. ResultsIn this study, 93 patients with epilepsy were enrolled; among them, 9 patients were lost to follow-up (attrition rate, 9.7 %), and 84 were included in the analysis. Five patients with unknown efficacy discontinued taking PER early due to intolerable adverse reactions, and 79 patients (48 males, 31 females; mean age, 11.0 ± 3.9 years) finally remained. Genetic epilepsy and structural epilepsy were found in 22 patients and 36 patients, respectively. The mean duration of epilepsy history at the time of PER initiation was 4.0 ± 3.8 years, and the mean maintenance dosage of add-on PER was 4.5 ± 1.8 mg/day (equivalent to 0.14 ± 0.07 mg/kg/day). Among the 79 patients, 28 patients were diagnosed with epilepsy syndrome, including 13 patients having self-limited epilepsy with centrotemporal spikes, among whom 9 patients were seizure-free after adding PER during the 6-month follow-up (seizure-free rate, 69.2 %). For these 79 patients, the seizure-free, response, and retention rates at the end of follow-up were 45.6 %, 74.7 %, and 82.1 %, respectively. Among the 84 patients included in the analyses, adverse reactions occurred in 20 patients, mainly dizziness (8 patients), somnolence (6 patients), and irritability (4 patients), and 4 patients developed two adverse reactions simultaneously. Univariate analyses revealed statistically significant differences in efficacy between groups with structural and non-structural epilepsy and between groups with different baseline concomitant ASMs, suggesting that these factors affected the efficacy of PER as the first add-on therapy. ConclusionThe overall response rate of PER as the first add-on therapy for children and adolescents with epilepsy who were followed up for 6 months was 74.7 %, indicating a relatively favorable safety and tolerability profile. The group of the baseline concomitant ASM administered and the etiological classification of epilepsy as either structural or non-structural were the factors influencing the efficacy of PER as the first add-on therapy.

Is Vaginal Progesterone More Effective to Treat Threatened Preterm Labour than Oral Nifedipine?

Objective: To compare the effectiveness of vaginal progesterone versus oral nifedipine in the treatment of threatened preterm labor (TPL).&#x0D; Methodology: This randomized control trial was carried out at Gynae and OBS department of Ibn-E-Siena Hospital, Multan, during a period of six months from December 2020 to June 2021. Participants were randomly allocated to either the vaginal progesterone group or the oral nifedipine group using computer-generated randomization. In Group A, participants received oral nifedipine at a dose of 20mg every 30 minutes for three initial doses, followed by long-acting nifedipine SR 20mg every 12 hours until reaching 37 weeks of gestational age or until cervical dilation exceeded 4cm. In Group B, participants were instructed to use vaginal micronized progesterone tablets at a dosage of 200mg once daily until reaching 37 weeks of gestational age or until cervical dilation exceeded 4cm. Effectiveness, refers to the ability of each treatment option to successfully prolong pregnancy duration in cases of threatened preterm labor.&#x0D; Results: The mean age of the subjects was 29.6 years, with a standard deviation of 5.44 years. Mean gestational age was 33.32 weeks. In Group A, oral nifedipine showed effectiveness in (73.0%) of the cases. Conversely, Group B, which received vaginal progesterone, exhibited significantly higher efficacy rates, among 57 (90.5%) of the patients (p-value of 0.011). Effectiveness among two treatment modalities was found to be statistically insignificant according to age and parity of the women (p=&gt;0.05).&#x0D; Conclusion: Study revealed a significant difference in efficacy between the two treatment modalities. Specifically, vaginal progesterone demonstrates superior efficacy compared to oral nifedipine, which underscores the potential advantages of vaginal progesterone in managing threatened preterm labor.

Efficacy and Safety of Switching from Adalimumab Originator to SB5, Adalimumab Biosimilar for Noninfectious Uveitis

ABSTRACT Purpose To evaluate the efficacy and safety of switching from adalimumab originator (Humira, AbbVie) to SB5, adalimumab biosimilar (Adalloce, Samsung Bioepis) in patients with noninfectious uveitis (NIU). Methods Fifteen patients (29 eyes) with NIU who were switched from adalimumab originator to SB5 and followed up for 6 months or longer were retrospectively included. Data consisted of best-corrected visual acuity (BCVA, logMAR), intraocular pressure (IOP, mmHg), anterior chamber (AC) cell grade, anterior vitreous (AV) cell grade, vitreous haze grade, central macular thickness (CMT, μm), and macular volume (MV, mm3) at pre-switching, 2, 4, and 6 months post-switching. Results There were no significant differences in BCVA, AC and AV cell grades, and vitreous haze grades at 2, 4, and 6 months post- compared with pre-switching, and no significant differences in CMT and MV at 2 and 6 months post-switching. CMT and MV decreased from 260.55 ± 67.44 μm and 8.37 ± 1.14 mm3 at pre-switching to 244.14 ± 60.31 μm (p = 0.032) and 8.11 ± 1.20 mm3 (p = 0.027) at 4 months post-switching, respectively. There was no recurrence of uveitis, as defined by AC cell grade, vitreous haze, or BCVA. Four patients (27%) were switched back to adalimumab originator after a mean of 9 weeks, due to discomfort during the injection (three patients) and technical difficulty with the new injection device (one patient). No other adverse events occurred after switching to SB5. Conclusion Switching from adalimumab originator to SB5 for NIU does not result in clinically significant differences in treatment efficacy and safety.

Definitive radio(chemo)therapy versus upfront surgery in the treatment of HPV-related localized or locally advanced oropharyngeal squamous cell carcinoma.

The treatment of stage I-III HPV+ oropharyngeal squamous cell carcinoma (HPV-OPSCC) is based on either surgery ± adjuvant therapy or exclusive radio±chemotherapy. We sought to compare these two therapeutic strategies in terms of efficacy, tolerance and quality of life (QoL). Patients treated for stage I-III HPV-OPSCC from 2010 to 2021 in 3 academic centers were included and sorted according to the treatment strategy: surgery or exclusive radio±chemotherapy. Efficacy and tolerance were retrospectively assessed, and a transversal exploratory QoL assessment was performed using QoL instruments. A total of 83 patients were included, with 21 undergoing non-minimally invasive surgery and 62 receiving definitive radio-±chemotherapy. 2-year progression-free survival (PFS) and overall survival (OS) were respectively 80% and 86% in the surgical group and 92% and 95% in the non-surgical group, with no significant difference. At the end of treatment, 64.5% of patients presented with a grade III toxicity, without significant difference between the two groups. No patient had late grade III toxicity at 24 months. Forty-five patients (11 in the surgical group, 34 in the non-surgical group) participated in an exploratory quality-of-life analysis. Patients reported significantly more fatigue and loss of appetite after surgery, whereas patients in the radio±chemotherapy group described significantly more salivary and oral problems and difficulty swallowing, but the median time between treatment completion and the response to the questionnaires. There was no significant difference in efficacy, physician-reported toxicity and overall patient-reported quality of life was found between non-minimally invasive surgery and radio±chemotherapy in the treatment of stage I-III HPV-OPSCC.

The impact of ketorolac and paracetamol on post-operative pain and analgesic consumption post-dental extraction

Background: Despite being very popular, there is limited direct comparative research that has evaluated their efficacy in post-extraction pain control between ketorolac and paracetamol. Those undertaken have shown varied results; some show that ketorolac is superior in pain relief and duration of action and others show no significant difference in efficacy between the two. This discrepancy underlines the need for further research that is important in determining the relative efficacy of the two analgesics in those patients undergoing dental extractions, something that is very important in guiding the choice of analgesic for the clinician to use in the emergency room for dental patients. Aims and Objectives: This study aimed to compare the analgesic efficacy of paracetamol (500 mg) and ketorolac (10 mg) in managing acute pain following dental extractions. Materials and Methods: A prospective, randomized, and double-blind controlled trial was conducted on 80 patients undergoing single tooth extraction. Participants were allocated to receive either paracetamol 500 mg or ketorolac 10 mg orally post-extraction. Pain intensity was assessed using the visual analog scale at predetermined intervals post-extraction. Secondary outcomes included time to first analgesic request besides total analgesic consumption over 24 h. Results: Patients from Group II (ketorolac) demonstrated lower intensity pain scores at all-time points post-extraction compared to Group I (paracetamol). On the other hand, Group-I (ketorolac) demonstrated an extended time to the first analgesic request (P = 0.914) and lower total analgesic consumption (P = 0.0001) in the first 24-h post-extraction than Group-I (paracetamol). Conclusion: Ketorolac (10 mg) functioned better for pain than paracetamol (500 mg) in reducing pain intensity following dental extractions, with a longer duration of analgesic effect and reduced need for additional analgesia. These findings suggest that ketorolac may be preferred over paracetamol for immediate post-operative pain management within dental extractions, considering patient-specific contraindications and risk factors.

Comparative Efficacy of Drug Interventions for Keloids: A Network Meta-analysis.

Keloids are common benign skin lesions originating from a disorganized fibroproliferative collagen response; these lesions often lead to both physical and psychological problems. The optimal treatment for keloids is yet to be standardized. Intralesional injection, which is simple and nontraumatic, is one of the most commonly used treatment modalities for these lesions. In this study, we compared 5 different drugs (intralesional injections) for the treatment of keloids in terms of efficacy. We systemically searched relevant studies on PubMed, EMBASE, and Cochrane Library. Randomized clinical trials on the safety and efficacy of triamcinolone acetonide (TAC), 5-fluorouracil (5-FU), botulinum toxin A (BTA), verapamil, and bleomycin were included in this study. This network meta-analysis included a total of 1114 patients from 20 randomized controlled trials. Botulinum toxin A alone and TAC plus 5-FU exhibited significantly better efficacy than did 5-FU, TAC, and verapamil. No significant difference in efficacy between BTA alone and TAC combined with 5-FU was observed. No significant differences were noted in the adverse event rate between BTA, TAC plus 5-FU, 5-FU, and TAC. Furthermore, we performed surface under the cumulative ranking curve analyses to predict the rank of each intervention (by efficacy and adverse event rate). The predicted ranking by efficacy was as follows: TAC plus 5-FU, BTA, bleomycin, TAC, 5-FU, and verapamil; the predicted ranking by adverse events was as follows: TAC, 5-FU, TAC plus 5-FU, and BTA. Funnel plot analysis revealed no publication bias. Botulinum toxin A and TAC plus 5-FU appear to have outstanding therapeutic efficacy for keloids. The rate of adverse events was similar among BTA, TAC, 5-FU, and TAC plus 5-FU. Nonetheless, additional reviews of rigorous, large-scale randomized controlled trials are warranted for further validation of our findings.

Efficacy and Safety of Topical Dapsone for Acne Vulgaris: A Systemic Review with Meta‐Analysis

Topical dapsone is an alternative medication for acne treatment. However, which topical dapsone formulation is superior remains uncertain. Furthermore, data on the efficacy of dapsone compared with other topical acne treatments are lacking. We aimed to review the efficacy and safety of topical dapsone at different concentrations and to compare it with other topical acne treatments. We systematically reviewed literature related to the use of topical dapsone in treating acne published from January 2005 to September 2022. We searched databases from selected research studies for inclusion criteria and performed a network meta‐analysis to compare the efficacy of using dapsone at different concentrations. Nine eligible studies were identified; among these, two studies with 7,350 patients were analyzed using network meta‐analysis. At 12 weeks, the percentage of achieving a Global Acne Assessment Score and the mean percentage reduction in inflammatory acne were higher with 7.5% than with 5% dapsone, but the difference was not statistically significant. However, the mean percentage reduction in noninflammatory acne and total acne lesion‐count at 12 weeks was lower with 7.5% than with 5% dapsone, but the difference was not statistically significant. Both concentrations of dapsone were more effective in treating inflammatory than comedonal acne and particularly effective in female patients and those aged ≥18 years. The side effects of dapsone were mild. Thus, topical dapsone is an effective alternative treatment for acne. Both concentrations of topical dapsone are effective in treating acne with no significant difference in efficacy and minimal side effects.

Therapeutic efficacy of probiotics for symptoms of attention-deficit hyperactivity disorder in children and adolescents: meta-analysis.

The efficacy of probiotics as a therapeutic alternative for attention-deficit hyperactivity disorder (ADHD) remain unclear. To investigate the effectiveness of probiotics for symptoms of ADHD and identify possible factors affecting their efficacy. Randomised placebo-controlled trials were identified through searching major databases from inception to April 2023, using the main keywords 'probiotics' and 'ADHD' without limitation on languages or geographic locations. The outcome of interest included improvement in total symptoms of ADHD, symptoms of inattention and hyperactivity/impulsivity, and drop-out rate. Continuous and categorical data were expressed as effect sizes based on standardised mean differences (SMDs) and odds ratios, respectively, with 95% confidence intervals. Meta-analysis of seven trials involving 379 participants (mean age 10.37 years, range 4-18 years) showed no significant improvement in total symptoms of ADHD (SMD = 0.25; P = 0.12), symptoms of inattention (SMD = 0.14; P = 0.3) or hyperactivity/impulsivity (SMD = 0.08; P = 0.54) between the probiotic and placebo groups. Despite non-significance on subgroup analyses, there was a large difference in effect size between studies using probiotics as an adjunct to methylphenidate and those using probiotics as supplementation (SMD = 0.84 v. 0.07; P = 0.16), and a moderate difference in effect size between studies using multiple strains of probiotics and those using single-strain regimens (SMD = 0.45 v. 0.03; P = 0.19). Current evidence shows no significant difference in therapeutic efficacy between probiotics and placebos for treatment of ADHD symptoms. However, albeit statistically non-significant, higher therapeutic efficacies associated with multiple-strain probiotics or combining probiotics with methylphenidate may provide direction for further research.

UGT1A4*3 polymorphism influences serum concentration and therapeutic effect of lamotrigine for epilepsy treatment: A meta-analysis.

Lamotrigine as a broad-spectrum antiepileptic drug, is widely applied and its clinical efficacy is highly recognized. However, significant differences are observed in blood drug concentration of lamotrigine among individuals, which may have an impact on its efficacy. UGT1A4 is the main metabolic enzyme. However, it was inconsistent for the influence of UGT1A4 genetic polymorphism on concentration and efficacy of lamotrigine therapy. This study aimed to evaluate the influences of UGT1A4*3 genetic polymorphisms on lamotrigine concentration and therapeutic effect through meta-analysis. The literature search was conducted in Medline, Embase, PubMed, Web of Science, Wan Fang Database, China National Knowledge Infrastructure, China Science and Technology Journal Database until January 2024. The primary outcome included the mean serum concentration, concentration-to-dose-ratio by body weight (CDR), or efficacy related to different UGT1A4*3 genotype for lamotrigine therapy. Data were collected to access the Mean Difference or odds ratio with 95% confidence interval. Meta-analysis was performed by RevMan 5.2. A total of eleven studies were enrolled. The meta-analysis for mean serum concentration of lamotrigine showed no significant difference between patients carrying TT genotypes and TG and GG genotypes group (MD: 0.12, 95% [-0.35, 0.58], P = 0.62). There was significant difference in CDR (MD: 0.49, 95% [0.03, 0.94], P = 0.04) and therapeutic efficacy (OR: 7.18, 95% [4.01, 12.83], P<0.00001) of lamotrigine, however no significant difference was found in subgroup analysis of CDR of children (MD: 0.03, 95% [-0.35, 0.42], P = 0.87) between patients carrying TT genotypes and TG and GG genotypes group. Polymorphism of UGT1A4*3 influenced the CDR and therapeutic efficacy of lamotrigine for antiepileptic therapy. Genotype analysis provided reference for personalized medication in the future. However, more high-quality evidences are necessary for precise and definitive conclusion.

Methylprednisolone use in hospitalised COVID-19 patients: a retrospective study.

Trials have demonstrated the benefits of methylprednisolone in the treatment of coronavirus disease 2019 (COVID-19). However, data on optimal dose, duration and timing of administration are limited. This study investigates the outcome of various methylprednisolone treatment regimens among hospitalised COVID-19 patients. A retrospective cohort study was conducted on hospitalised adult COVID-19 patients admitted between June and August 2021 in general COVID-19 wards, treated with methylprednisolone. Clinical outcomes evaluated include in-hospital mortality, thirty-day mortality, clinical efficacy (C-reactive protein (CRP), total white blood cells (TWBC) and oxygen requirement) as well as the safety of methylprednisolone. Of 278 patients, 1(0.4%) received weight-based dosing of 1 mg/kg/day, 101(36.3%) received weight-based dosing of 2 mg/kg/day, 130(46.8%) received fixed dosing methylprednisolone 250 mg/day and 46(16.5%) received fixed dosing methylprednisolone 500 mg/day. There was a significant difference in in-hospital mortality rates following different methylprednisolone doses whereby in-hospital mortality occurred in 22.5% (n = 23) of patients with 1 or 2 mg/kg/day methylprednisolone, 32.3% (n = 42) with 250 mg/day and 39.1% (n = 18) with 500 mg/day (p = 0.023). On the other hand, no significant difference in thirty-day mortality, clinical efficacy and safety was observed between different dosing regimens (p > 0.05). The use of methylprednisolone weight-based dosing in hospitalised COVID-19 patients should be considered due to the positive outcome associated with lower in-hospital mortality.

Evaluation of the Efficacy and Safety of Oral Tofacitinib for the Treatment of Alopecia Areata in Children

Alopecia areata (AA) is a common chronic relapsing nonscarring alopecia. Severe forms of AA commonly manifest during childhood. Treatment of AA is challenging due to the variability of the disease course as well as unpredictable responses to treatment. There is no uniform approved treatment for cure or sustained remission in children till now. Tofacitinib emerged as a novel drug in the treatment of AA, but few studies have been conducted on its safety and efficacy in children. Limitation of this study includes retrospective nature, small sample size, and lack of prolonged follow‐up. Aim. This retrospective study aimed to assess the efficacy and safety of oral tofacitinib in children with AA. Method. In this retrospective study, we included patients aged 18 years or younger with AA. The scalp blandness of included patients was greater than 20% and they were on oral tofacitinib for at least two months. The demographic data, clinical characteristics, tofacitinib efficacy, and adverse effects were recorded. The primary endpoint was the last recorded percent change in the Severity of Alopecia Tool (SALT) score during treatment. Results. We included 26 patients (12 males and 14 females) with AA with a mean age of 11.6 ± 4.42 (3–18) years. Eighteen of them were in the alopecia areata (AA) group, whereas eight patients had alopecia totalis (AT) or alopecia universalis (AU). The mean disease duration before starting treatment with tofacitinib was 3.9 ± 3.3 years. Most of the patients were on a tofacitinib daily dose of 5 mg (53.85%) and 10 mg (38.46%). Patients were on tofacitinib for 6.73 ± 3.79 months. The patients’ baseline SALT score was recorded as 68.58 ± 32.65 and the final SALT score was 17.65 ± 23.88. Thus, the patients achieved a 50.92% reduction in the SALT score. Interestingly, there were no statistically significant differences in clinical efficacy between subtypes of AA and AT/AU. Conclusion. Tofacitinib was significantly effective in treating AA and AT/AU in children, with mild tolerable adverse effects, although relapse during treatment and tapering was recorded. Future randomized clinical trials with longer follow‐up periods are needed to evaluate the safety of oral tofacitinib in children.

Efficacy and safety of a proposed omalizumab biosimilar compared to the reference product in the management of uncontrolled moderate-to-severe allergic asthma: a multicenter, phase III, randomized, double-blind, equivalency clinical trial.

Allergic asthma has a considerable burden on the quality of life. A significant portion of moderate-to-severe allergic asthma patients need omalizumab, an anti-immunoglobulin-E monoclonal antibody, as an add-on therapy. In this phase III clinical trial P043 (Zerafil®, CinnaGen, Iran) efficacy, safety, and immunogenicity were compared with Xolair® (the originator omalizumab). The primary outcome was the rate of protocol-defined asthma exacerbations. Exacerbation rates, Asthma Control Test (ACT) results, spirometry measurements, immunogenicity, and safety were evaluated. Each subject received either medication with a dose ranging from 150 to 375 mg based on pre-treatment serum total IgE level (IU/mL) and body weight (kg) every two or four weeks for a duration of 28 weeks. Exacerbation rates were 0.150 (CI: 0.079-0.220) in the P043 group, and 0.190 (CI: 0.110-0.270) in the omalizumab group (per-protocol). The least squares mean differences of predicted Forced Expiratory Volume in the First second (FEV1) were -2.51% (CI: -7.17-2.15, P=0.29) and -3.87% (CI: -8.79-1.04, P=0.12), pre- and post-bronchodilator use. The mean ± SD of ACT scores at the screening and the last visit were 10.62 ± 2.93 and 20.93 ± 4.26 in P043 and 11.09 ± 2.75 and 20.46 ± 5.11 in the omalizumab group. A total of 288 adverse events were reported for the 256 enrolled participants. Among all, "dyspnea" and "headache" were the most reported ones. The overall incidence of adverse events (P=0.62) and serious adverse events (P=0.07) had no significant differences between the two groups. None of the samples were positive for anti-drug antibodies. P043 was equivalent to omalizumab in the management of asthma in reduction of exacerbations. There was no significant difference in other efficacy and safety parameters. www.clinicaltrials.gov (NCT05813470) and www.IRCT.ir (IRCT20150303021315N20).

Treatment for Osteoporotic Vertebral Fracture - A Short Review of Orthosis and Percutaneous Vertebroplasty and Balloon Kyphoplasty.

The management of osteoporotic vertebral fractures (OVFs) in the elderly includes nonoperative treatment and vertebroplasty, but has not been established due to the diversity of patient backgrounds. The purpose of this study was to compare the impact of 3 treatment modalities for the management of OVF: orthotic treatment, percutaneous vertebroplasty (PVP), and balloon kyphoplasty (BKP). The method was based on an analysis of the latest RCTs, meta-analyses, and systematic reviews on these topics. No study showed a benefit of bracing with high level of evidence. Trials were found that showed comparable outcomes without orthotic treatment. Only 1 randomized controlled trial (RCT) showed an improvement in pain relief up to 6 months compared with no orthosis. Rigid and nonrigid orthoses were equally effective. Four of 5 RCTs comparing vertebroplasty and sham surgery were equally effective, and one RCT showed superior pain relief with vertebroplasty within 3 weeks of onset. In open trials comparing vertebroplasty with nonoperative management, vertebroplasty was superior. PVP and BKP were comparable in terms of pain relief, improvement in quality of life, and adjacent vertebral fractures. BKP does not affect global sagittal alignment, although BKP may restore vertebral body height. An RCT was published showing that PVP was effective in chronic cases without pain relief. Vertebroplasty improved life expectancy by 22% at 10 years. The superiority of orthotic therapy for OVF was seen only in short-term pain relief. Soft orthoses proved to be a viable alternative to rigid orthoses. Vertebroplasty within 3 weeks may be useful. There is no significant difference in clinical efficacy between PVP and BKP. Vertebroplasty improves life expectancy.

Comparison of Efficacy of Single Application Topical 5% Permethrin versus Single Dose Oral Ivermectin in the Treatment of Scabies

Aim: To compare the efficacy of a single application of topical 5% permethrin versus a single dose of oral ivermectin in the treatment of scabies. Methodology: Randomized controlled trial. Department of Dermatology, Pak Emirates Military Hospital (PEMH), Rawalpindi, from January 1, 2021, to June 30, 2021. Sixty scabies patients of both genders were included. 30 patients for 5% permethrin cream (group A), and 30 patients for the oral ivermectin group (group B). Follow-up with patients was done at weeks 1 and 2 after treatment. Age in this study was &gt; 5 years. Results: The mean of age was 27.700±8.43 years, duration of disease was 5.133±1.71 weeks, and weight was 71.366±11.31 kg in Group A, while in Group B, age was 30.366±9.37 years, duration of disease was 4.700±1.55 weeks, and weight was 73.433±10.82 kg. Efficacy was observed in 22 (73.3%) patients in group A and 21 (70%) patients in group B (P = 0.775). Conclusion: There is no significant efficacy difference between topical permethrin and oral ivermectin in treatment of scabies. Keywords: Efficacy, Permethrin, Ivermectin, Scabies