Displaying publications 1 - 20 of 358 in total

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  1. Lapeña JFF, Munk PL, Saw A, Peh WC
    Med J Aust, 2019 05;210(8):347-348.e1.
    PMID: 30945753 DOI: 10.5694/mja2.50131
    Matched MeSH terms: Double-Blind Method*
  2. Rastogi A, Kulkarni SA, Deshpande SK, Driver V, Barman H, Bal A, et al.
    Adv Wound Care (New Rochelle), 2023 Aug;12(8):429-439.
    PMID: 36245145 DOI: 10.1089/wound.2022.0093
    We aimed to assess safety and dose-finding efficacy of esmolol hydrochloride (Galnobax) for healing of diabetic foot ulcer (DFU). This is phase 1/2 multicenter, randomized, double-blind vehicle-controlled study. Participants having diabetes and noninfected, full-thickness, neuropathic, grade I or II (Wagner classification) DFU, area 1.5-10 cm2, and unresponsive to standard wound care (at least 4 weeks) were randomized to receive topical Galnobax 14% twice daily (BID), Galnobax 20% BID, Galnobax 20% once daily (OD)+vehicle, or vehicle BID with standard of care. The primary efficacy end point was the reduction in area and volume of target ulcer from baseline to week 12 or wound closure, whichever was earlier. The wound duration was 12.5 weeks (5-49.1 weeks) and wound area 4.10 ± 2.41 cm2 at baseline. The ulcer area reduction was 86.56%, 95.80%, 80.67%, and 82.58% (p = 0.47) in the Galnobax 14%, Galnobax 20%, Galnobax20%+vehicle, and vehicle only groups, respectively. Ulcer volume reduction was 99.40% in the Galnobax14%, 83.36% in Galnobax20%, 55.41% in the Galnobax20%+vehicle, and 84.57% in vehicle group (p = 0.86). The systemic concentration of esmolol was below the quantification limit (10 ng/mL) irrespective of doses of Galnobax (Cmax esmolol acid 340 ng/mL for 14% Galnobax, AUC 2.99 ± 4.31 h*μg/mL after single dose). This is the first clinical study of the short acting beta blocker esmolol hydrochloride used as novel formulation for healing of DFU. We found that esmolol when applied topically over wounds had minimal systemic concentration establishing its safety for wound healing in patients with diabetes. Esmolol hydrochloride is a safe novel treatment for DFU.
    Matched MeSH terms: Double-Blind Method
  3. Candelaria M, González DE, Delamain MT, Bär DO, Beniwal SK, Dasappa L, et al.
    Leuk Lymphoma, 2019 12;60(14):3375-3385.
    PMID: 31272251 DOI: 10.1080/10428194.2019.1633632
    This multicenter, double-blind, randomized study compared the efficacy, pharmacokinetics (PKs)/pharmacodynamics (PDs), safety and immunogenicity profile of RTXM83 vs. reference rituximab (R-rituximab), both with CHOP, as first-line treatment of diffuse large B-cell lymphoma (DLBCL). A total of 272 patients <65 years of age, with good prognosis (136 per arm) were randomized (1:1) to receive six cycles of either RTXM83 or R-rituximab. The primary efficacy endpoint was achieved (overall response rate of 83.6% for RTXM83 and 82.9% for R-rituximab) with a difference 0.7% between arms (95%CI: [-8.77% to 10.17%]) fulfilling the predefined non-inferiority margin (-13%). Similar number of patients reported at least one adverse event (AE) (131 per arm) or one serious AE (47 with RTXM83 and 45 with R-rituximab). Anti-drug antibody development was comparable between the arms. PK/PD secondary endpoint results support similarity between the compounds. RTXM83 exhibits non-inferior efficacy and similar safety/immunogenicity to R-rituximab, being an accessible alternative for the treatment of patients with previously untreated DLBCL.
    Matched MeSH terms: Double-Blind Method
  4. Tan AH, Lim SY, Mahadeva S, Loke MF, Tan JY, Ang BH, et al.
    Mov Disord, 2020 12;35(12):2250-2260.
    PMID: 32894625 DOI: 10.1002/mds.28248
    BACKGROUND: Helicobacter pylori (HP) infection has been associated with worse motor function in Parkinson's disease (PD).

    OBJECTIVE: We aimed to evaluate the effects of HP eradication on PD symptoms.

    METHODS: In this parallel-group, double-blind, randomized placebo-controlled, single-center trial, patients with PD with positive HP urea breath test and serology were block randomized (1:1) to receive standard eradication triple therapy or identically appearing placebo capsules for 1 week. Prespecified motor (International Parkinson and Movement Disorder Society Unified PD Rating Scale [MDS-UPDRS], timed tests, and home-based wearable sensor measurements), nonmotor (Leeds Dyspepsia Questionnaire and Montreal Cognitive Assessment), and quality-of-life (Parkinson's Disease Questionnaire-39) outcome measures were assessed at weeks 6, 12, 24, and 52. The primary outcome was the baseline-to-week 12 change in ON medication MDS-UPDRS motor scores. Lactulose-hydrogen breath testing for concomitant small intestinal bacterial overgrowth was performed at baseline and repeated at week 24, together with the urea breath test.

    RESULTS: A total of 310 patients were screened for eligibility and 80 were randomly assigned, of whom 67 were included in the full-analysis set (32 treatment group patients, 35 placebo patients). HP eradication did not improve MDS-UPDRS motor scores at week 12 (mean difference 2.6 points in favor of placebo, 95% confidence interval: -0.4 to 5.6, P = 0.089). There was no significant improvement in any motor, nonmotor, or quality-of-life outcome at weeks 12 and 52. Both the full-analysis and per-protocol analyses (based on eradication status) supported these conclusions. Small intestinal bacterial overgrowth status did not influence treatment results.

    CONCLUSIONS: HP eradication does not improve clinical outcomes in PD, suggesting that there is no justification for routine HP screening or eradication with the goal of improving PD symptoms. © 2020 International Parkinson and Movement Disorder Society.

    Matched MeSH terms: Double-Blind Method
  5. Bosch J, Lonn EM, Jung H, Zhu J, Liu L, Lopez-Jaramillo P, et al.
    Eur Heart J, 2021 08 17;42(31):2995-3007.
    PMID: 33963372 DOI: 10.1093/eurheartj/ehab225
    AIMS: Rosuvastatin (10 mg per day) compared with placebo reduced major adverse cardiovascular (CV) events by 24% in 12 705 participants at intermediate CV risk after 5.6 years. There was no benefit of blood pressure (BP) lowering treatment in the overall group, but a reduction in events in the third of participants with elevated systolic BP. After cessation of all the trial medications, we examined whether the benefits observed during the active treatment phase were sustained, enhanced, or attenuated.

    METHODS AND RESULTS: After the randomized treatment period (5.6 years), participants were invited to participate in 3.1 further years of observation (total 8.7 years). The first co-primary outcome for the entire length of follow-up was the composite of myocardial infarction, stroke, or CV death [major adverse cardiovascular event (MACE)-1], and the second was MACE-1 plus resuscitated cardiac arrest, heart failure, or coronary revascularization (MACE-2). In total, 9326 (78%) of 11 994 surviving Heart Outcomes Prevention Evaluation (HOPE)-3 subjects consented to participate in extended follow-up. During 3.1 years of post-trial observation (total follow-up of 8.7 years), participants originally randomized to rosuvastatin compared with placebo had a 20% additional reduction in MACE-1 [95% confidence interval (CI), 0.64-0.99] and a 17% additional reduction in MACE-2 (95% CI 0.68-1.01). Therefore, over the 8.7 years of follow-up, there was a 21% reduction in MACE-1 (95% CI 0.69-0.90, P = 0.005) and 21% reduction in MACE-2 (95% CI 0.69-0.89, P = 0.002). There was no benefit of BP lowering in the overall study either during the active or post-trial observation period, however, a 24% reduction in MACE-1 was observed over 8.7 years.

    CONCLUSION: The CV benefits of rosuvastatin, and BP lowering in those with elevated systolic BP, compared with placebo continue to accrue for at least 3 years after cessation of randomized treatment in individuals without cardiovascular disease indicating a legacy effect.

    TRIAL REGISTRATION NUMBER: NCT00468923.

    Matched MeSH terms: Double-Blind Method
  6. Lee JW, Griffin M, Kim JS, Lee Lee LW, Piatek C, Nishimura JI, et al.
    Lancet Haematol, 2023 Dec;10(12):e955-e965.
    PMID: 38030318 DOI: 10.1016/S2352-3026(23)00315-0
    BACKGROUND: Symptoms of anaemia due to clinically significant extravascular haemolysis can affect patients with paroxysmal nocturnal haemoglobinuria (PNH) treated with C5 inhibitors (ravulizumab or eculizumab). The aim of this study was to assess the efficacy and safety of danicopan (ALXN2040), an investigational, first-in-class, oral complement factor D inhibitor, as add-on therapy to ravulizumab or eculizumab in patients with PNH and clinically significant extravascular haemolysis.

    METHODS: ALPHA is an ongoing, international, phase 3, randomised, double-blind, placebo-controlled trial evaluating danicopan as add-on therapy to ravulizumab or eculizumab. Eligible patients were adults (age ≥18 years) with PNH and clinically significant extravascular haemolysis (haemoglobin ≤9·5 g/dL; absolute reticulocyte count ≥120 × 109/L) on ravulizumab or eculizumab for at least 6 months. Patients were randomly assigned (2:1) to danicopan or placebo added to ravulizumab or eculizumab for 12 weeks using an interactive response technology system. Randomisation was stratified based on transfusion history, haemoglobin, and patients enrolled from Japan. The initial oral danicopan dose was 150 mg three times a day; escalation to 200 mg three times a day was permitted based on clinical response. The infusion dose level of eculizumab (every 2 weeks) ranged from 900 mg to 1500 mg, and for ravulizumab (monthly or every 8 weeks) ranged from 3000 mg to 3600 mg. The primary endpoint was change in haemoglobin concentration from baseline to week 12. Here we present the protocol-prespecified interim analysis, planned when approximately 75% of participants were randomly assigned to treatment and completed or discontinued at 12 weeks. This trial is registered with ClinicalTrials.gov (NCT04469465).

    FINDINGS: Individuals were randomly assigned between Dec 16, 2020, and Aug 29, 2022. At data cutoff (June 28, 2022), 73 individuals were randomly assigned, received treatment, and were analysed for safety (danicopan, n=49; placebo, n=24). The protocol-prespecified interim efficacy analysis set included the first 63 participants (danicopan, n=42; placebo, n=21). At week 12, danicopan plus ravulizumab or eculizumab increased haemoglobin versus placebo plus ravulizumab or eculizumab (least squares mean [LSM] change from baseline: danicopan, 2·94 g/dL [95% CI 2·52 to 3·36]; placebo, 0·50 g/dL [-0·13 to 1·12]; LSM difference, 2·44 g/dL [1·69 to 3·20]; p<0·0001). Grade 3 adverse events in the danicopan group were increased alanine aminotransferase (two [4%] of 49 patients), leukopenia (one [2%]), neutropenia (two [4%]), cholecystitis (one [2%]), COVID-19 (one [2%]), increased aspartate aminotransferase (one [2%]), and increased blood pressure (one [2%]), and in the placebo group were anaemia (one [4%] of 24 patients), thrombocytopenia (one [4%]), and asthenia (one [4%]). The serious adverse events reported in the danicopan group were cholecystitis (one [2%] patient) and COVID-19 (one [2%]) and in the placebo group were anaemia and abdominal pain, both in one (4%) patient. There were no serious adverse events related to study drug or deaths reported in the study.

    INTERPRETATION: These primary efficacy and safety results show that danicopan as add-on treatment to ravulizumab or eculizumab significantly improved haemoglobin concentrations at week 12 with no new safety concerns, suggesting an improved benefit-risk profile in patients with PNH and clinically significant extravascular haemolysis.

    FUNDING: Alexion, AstraZeneca Rare Disease.

    Matched MeSH terms: Double-Blind Method
  7. Kamala F, Boo NY, Cheah FC, Birinder K
    Acta Paediatr, 2002;91(12):1350-6.
    PMID: 12578294
    AIM: To determine whether the addition of heparin to total parenteral nutrition (TPN) fluid would prevent blockage of peripherally inserted central catheters (PICCs) in neonates.

    METHODS: This was a randomized, double-blind, controlled study of 66 eligible neonates with PICCs inserted for the administration of TPN. Infants were randomized to receive TPN containing either 1 IU ml(-1) of heparin (n = 35) or no heparin (n = 31).

    RESULTS: There was no significant difference in the incidence of blocked catheters between the two groups of infants (heparin: 14.3%; no-heparin: 22.6%, p = 0.4). Although a higher percentage (62.9%) of infants in the heparin group received a complete course of TPN successfully via PICC than those in the no-heparin group (48.4%), the difference was not statistically significant (p = 0.3). There were no significant differences in the incidence of catheter-related sepsis, hypertriglyceridaemia, hyperbilirubinaemia, coagulopathy or intraventricular haemorrhage between the two groups.

    CONCLUSION: Addition of heparin to TPN fluid was not associated with a significant reduction in the incidence of blocked PICCs. However, the sample size of this study was too small to exclude even rather marked differences between the groups.

    Matched MeSH terms: Double-Blind Method
  8. Jaradi H, Tay KH, Delilkan AE
    Med J Malaysia, 1989 Jun;44(2):143-6.
    PMID: 2626122
    The 'Priming principle' applied to non-depolarizing muscle relaxant atracurium was studied in 60 patients. This was a double blind study. The conditions observed for intubation were graded and the efficacy of priming dose of atracurium for shortening the onset time of intubation was studied. The patients were of ASA classification I and II and received standard premedication. The purpose of the study was to use the priming dose of atracurium to shorten the onset time of intubating dose of atracurium. This would be desirable in conditions requiring rapid intubation and in situations when the depolarizing muscle relaxant suxamethonium is contra-indicated. The results were statistically significant.
    Matched MeSH terms: Double-Blind Method
  9. Chan WK, Wong VW
    Lancet Gastroenterol Hepatol, 2019 10;4(10):747-749.
    PMID: 31345779 DOI: 10.1016/S2468-1253(19)30183-9
    Matched MeSH terms: Double-Blind Method
  10. Nagendrababu V, Aly Ahmed HM, Pulikkotil SJ, Veettil SK, Dharmarajan L, Setzer FC
    J Endod, 2019 Oct;45(10):1175-1183.e3.
    PMID: 31551112 DOI: 10.1016/j.joen.2019.06.008
    INTRODUCTION: This systematic review compared the anesthetic efficacy between Gow-Gates (GG), Vazirani-Akinosi (VA), and mental incisive (MI) nerve blocks (NBs) with inferior alveolar nerve blocks (IANBs) in mandibular teeth with irreversible pulpitis using meta-analysis and trial sequential analysis (TSA).

    METHODS: Studies were identified from 4 electronic databases up to June 2019. Randomized clinical trials (RCTs) comparing the anesthetic success rate of GG, VA, and MI NBs with IANBs in mandibular premolars and molars with irreversible pulpitis were included. The quality of selected RCTs was appraised using the revised Cochrane risk of bias tool. Random-effects meta-analyses of risk ratio (RR) and 95% confidence intervals (CIs) were calculated, and random errors were evaluated by TSA. The quality of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation approach.

    RESULTS: Five RCTs were included; 2 of them were classified as low risk of bias. No significant difference was observed in the anesthesia success rate compared between GG and IA NBs (RR = 1.10; 95% CI, 0.82-1.48; I2 = 0%). Similarly, no difference was evident between MINB and IANB (RR = 1.15; 95% CI, 0.97-1.36; I2 = 0%). Overall, the cumulative success rates for the 3 anesthetic techniques were low. TSA showed a lack of firm evidence for the results of the meta-analysis between GG NB and IANB. The Grading of Recommendations, Assessment, Development and Evaluation approach evaluation showed that the evidence was of moderate quality for GG NB and IANB compared with low quality for MI and IA NBs. Because only 1 study was available comparing VA NB and IANB, a meta-analysis was not performed. The adverse effect associated with MI NB was swelling, whereas it was prolonged numbness for IANB.

    CONCLUSIONS: GG NB and IANB showed similar anesthetic efficacy compared with IANB in mandibular teeth with irreversible pulpitis. However, the success rates for each technique indicate the need for supplemental anesthesia. Further well-designed RCTs evaluating different anesthetic techniques with and without supplemental injection are required to provide stronger evidence.

    Matched MeSH terms: Double-Blind Method
  11. Theophilus SC, Adnan JS
    Malays J Med Sci, 2011 Jan;18(1):30-7.
    PMID: 22135571
    BACKGROUND: A double-blind randomised control study was conducted on all patients who were admitted or referred to the Department of Neurosurgery, Sultanah Aminah Hospital, Johor Bahru, with a diagnosis of hydrocephalus where a ventriculoperitoneal shunt was indicated.
    METHODS: The period of study was from November 2005 to May 2007, and the follow-up period was 3 months after surgery. Randomisation was carried out in the operating room prior to the procedure. The scrub nurse selected a sealed envelope, which contained the assignment of each patient to 1 of 2 treatment groups: Group 1 patients were treated with topical methicillin, and Group 2 patients were not treated with topical methicillin. Prophylactic antibiotic, cefuroxime (25 mg/kg) was given intravenously at induction. Standard sterile operative technique was followed in preparing and draping the patients.
    RESULTS: A total of 90 patients were recruited in the study, and 13 (14.4%) patients developed an infection within 3 months post-operation. Group 1 had a 8.9% risk of infection, and Group 2 had a 20% risk; however, there was no statistically significant post-operative ventriculoperitoneal shunt (VPS) infection reduction with the use of topical methicillin in VPS surgery (P = 0.230). Multivariate analysis showed that only duration of surgery had a significant influence on the incidence of post-operative VPS infection in the non-methicillin group (P = 0.02). The non-methicillin group had an 8 times greater risk of developing post-operative VPS infection than the methicillin group if surgery lasted longer than 1 hour.
    CONCLUSION: Topical methicillin had no significance in the reduction of post-operative VPS infection.
    KEYWORDS: methicillin; neurosurgery; post-operative wound infection; topical administration; ventriculoperitoneal shunt
    Study site: Patient admitted or referred to Hospital Sultanah Aminah Johor Bahru, Johor, Malaysia
    Matched MeSH terms: Double-Blind Method
  12. Aribi Al-Zoobaee FW, Yee Shen L, Veettil SK, Gopinath D, Maharajan MK, Menon RK
    PMID: 33265920 DOI: 10.3390/ijerph17238891
    Cancer therapy may be complicated and compromised by viral infections, including oral herpes simplex virus (HSV) infection. This network meta-analysis aimed to identify the best antiviral agent to prevent or treat oral HSV infection in patients being treated for cancer. A search was conducted for trials published since inception until the 10th of May 2020 in MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials. A network meta-analysis was performed on the data from randomized controlled trials that assessed antiviral agents for preventive or therapeutic activity vs. placebo, no treatment or any other active intervention in patients being treated for cancer. The agents were ranked according to their effectiveness in the prevention of oral HSV using surface under the cumulative ranking (SUCRA). Grading of Recommendations, Assessment, Development and Evaluations (GRADE) was used to assess the certainty of the evidence. In total, 16 articles were included. The pooled relative risk (RR) to develop oral HSV infection in the acyclovir group was 0.17 (95% CI: 0.10, 0.30), compared to 0.22 (95% CI: 0.06, 0.77) in the valacyclovir group. Acyclovir ranked highest for the prevention of oral HSV followed by valacyclovir. Subgroup analysis with different acyclovir regimens revealed that the best regimens in terms of HSV-1 prevention were 750 mg/m2 acyclovir administered intravenously followed by 1600 mg per day orally. Acyclovir (250 mg/m2 per day) administered intravenously was the least effective against the prevention of oral HSV.
    Matched MeSH terms: Double-Blind Method
  13. Muhd Helmi Azmi, Karis Misiran
    Medicine & Health, 2007;2(2):103-109.
    MyJurnal
    This was a prospective randomized double blind controlled study to compare intubating conditions at 60 seconds with rocuronium 0.6 mg/kg by using three different induction techniques: propofol-placebo (PP), propofol-ephedrine (PE) and propofol-placebo-crystalloid (PC). Ninety patients were included and randomly allocated to receive one of the three combinations. The  patients  were  induced  using  fentanyl 2 µg/kg,  followed by propofol 2.5 mg/kg with normal saline as placebo (Group PP and Group PC) or ephedrine 70  µg/kg  (Group PE)  given  over  30  seconds. Subsequently, rocuronium 0.6 mg/kg was given over five seconds and endotracheal intubations were performed 60 seconds later. Intubating conditions were clinically acceptable in all patients except in four patients in PP group, who had poor intubating conditions. The proportion of excellent intubating conditions was significantly highest in Group PE (94%) followed by Group PC (81%) and lowest in Group PP (50%). In conclusion, induction with propofol-ephedrine and propofol-placebo-crystalloid combinations rovided significantly better intubating conditions than propofol alone, when rocuronium 0.6 mg/kg was used for intubation at 60 seconds.
    Matched MeSH terms: Double-Blind Method
  14. Kumarasamy G, Ramli RR, Singh H, Abdullah B
    J Complement Integr Med, 2020 Dec 21;18(2):433-438.
    PMID: 34187130 DOI: 10.1515/jcim-2020-0001
    OBJECTIVES: Recurrence rate of nasal polyps is high following endoscopic sinus surgery. To improve the surgical outcome, steroid impregnated nasal dressing is used postoperatively We aimed to compare the effect of Tualang honey impregnated nasal dressing with steroid impregnated nasal dressing on wound healing and surgical outcomes in post endoscopic sinus surgery patients.

    METHODS: A prospective, randomized, controlled trial was carried out at two tertiary hospitals. 32 patients diagnosed with chronic rhinosinusitis and had underwent endoscopic sinus surgery were enrolled. The study group received 2 mL of Tualang honey nasal dressing and the control group received nasal dressing with 2 mL of triamcinolone 20 mg/mL as positive control. A 2 cm nasal dressing was placed longitudinally into the middle meatuses of both nasal cavities. Postoperative healing assessments of edema, crusting, secretions, scarring and symptoms were performed at postoperative day 7, 14, 28 and at 3 months using Sinonasal Outcome Test 22 questionnaire and modified Lund-Kennedy scoring system.

    RESULTS: There were no significant differences noted in the scores of Sinonasal Outcome Test 22 and modified Lund-Kennedy at Day 7, 14 and 28 (p>0.05) for both groups. At 3rd month, patients in the triamcinolone group had lesser symptoms and better endoscopic findings (p<0.05).

    CONCLUSION: Tualang honey is not as effective as steroid in achieving good wound healing and surgical outcomes in post endoscopic sinus surgery patients. Thus, it is not suitable as a substitute for steroid to reduce symptoms and prevent recurrence of disease.

    Matched MeSH terms: Double-Blind Method
  15. Yeoh AH, Tang SS, Abdul Manap N, Wan Mat WR, Said S, Che Hassan MR, et al.
    Turk J Med Sci, 2016 Apr 19;46(3):620-5.
    PMID: 27513234 DOI: 10.3906/sag-1502-56
    BACKGROUND/AIM: The effects of pericardium 6 (P6) electrical stimulation in patients at risk of postoperative nausea and vomiting (PONV) following laparoscopic surgery were evaluated.

    MATERIALS AND METHODS: Eighty patients for laparoscopic surgery with at least one of the determined risks (nonsmoker, female, previous PONV/motion sickness, or postoperative opioid use) were randomized into either an active or sham group. At the end of surgery, Reletex electrical acustimulation was placed at the P6 acupoint. The active group had grade 3 strength and the sham group had inactivated electrodes covered by silicone. It was worn for 24 h following surgery. PONV scores were recorded.

    RESULTS: The active group had significantly shorter durations of surgery and lower PONV incidence over 24 h (35.1% versus 64.9%, P = 0.024) and this was attributed to the lower incidence of nausea (31.4% versus 68.6%, P = 0.006). The overall incidence of vomiting was not significantly different between the groups, but it was higher in the sham group of patients with PONV risk score 3 (23.9%, P = 0.049).

    CONCLUSION: In patients at high risk for PONV, P6 acupoint electrical stimulation lowers the PONV incidence by reducing the nausea component. However, this reduction in nausea is not related to increasing PONV risk scores.

    Matched MeSH terms: Double-Blind Method
  16. Kato J, Baba M, Kuroha M, Kakehi Y, Murayama E, Wasaki Y, et al.
    Clin Ther, 2021 05;43(5):822-835.e16.
    PMID: 34059327 DOI: 10.1016/j.clinthera.2021.03.015
    PURPOSE: Mirogabalin besylate has been approved in several countries to treat peripheral neuropathic pain. This pooled analysis, using data from the two pivotal Phase III studies in Asian patients with diabetic peripheral neuropathic pain and post-herpetic neuralgia, aimed to provide clinicians with more detailed and precise information relating to mirogabalin's safety and efficacy.

    METHODS: Data were pooled from 2 multicenter, double-blind, placebo-controlled, parallel-group, 14-week treatment studies of mirogabalin conducted at ∼350 study sites (Japan, South Korea, Taiwan, Singapore, Malaysia, and Thailand). Eligible patients in both studies were randomized in a 2:1:1:1 ratio, stratified according to a baseline average daily pain score (ADPS) of <6 or ≥6, to placebo, mirogabalin 15-mg once daily (QD), mirogabalin 10-mg twice daily (BID), or mirogabalin 15-mg BID treatment groups. Safety was assessed based on treatment-emergent adverse events identified from the adverse events collected throughout both studies. The primary efficacy end point of both studies was the change from baseline in ADPS at week 14.

    FINDINGS: In total, 1587 patients (824 with diabetic peripheral neuropathic pain; 763 with post-herpetic neuralgia) who received at least 1 dose of study drug were analyzed (633 received placebo, 954 treated with mirogabalin). Treatment-emergent adverse events included somnolence (3.8%, 10.8%, 14.5%, and 19.1%) and dizziness (2.7%, 5.7%, 9.1%, and 13.1%) in patients receiving placebo, mirogabalin 15 mg QD, mirogabalin 10 mg BID, and mirogabalin 15 mg BID, respectively. In patients treated with mirogabalin 15 mg QD, 2 (0.6%) of 316 patients discontinued due to somnolence. In the mirogabalin 10-mg BID group, somnolence, edema, and peripheral edema each resulted in 3 (0.9%) of 318 patient discontinuations. In the mirogabalin 15-mg BID group, 6 (1.9%) of 320 patients discontinued due to dizziness and 3 (0.9%) due to somnolence. At week 14, mirogabalin 10 mg BID and 15 mg BID statistically significantly improved ADPS versus placebo, with least squares mean changes (95% CI) of -0.31 (-0.55, -0.08) and -0.63 (-0.86, -0.40). Post hoc analysis showed a statistically significant difference 2 days after administration in the mirogabalin 10-mg and 15-mg BID groups compared with placebo. Female sex, age ≥65 years, and baseline weight <60 kg may influence the safety of mirogabalin, particularly regarding the incidence of somnolence and dizziness, but had no notable impact on efficacy. ClinicalTrials.gov identifiers: NCT02318706 and NCT02318719.

    IMPLICATIONS: This pooled analysis showed that mirogabalin was efficacious and well-tolerated by Asian patients with peripheral neuropathic pain.

    Matched MeSH terms: Double-Blind Method
  17. Pszczolkowski S, Sprigg N, Woodhouse LJ, Gallagher R, Swienton D, Law ZK, et al.
    JAMA Neurol, 2022 May 01;79(5):468-477.
    PMID: 35311937 DOI: 10.1001/jamaneurol.2022.0217
    IMPORTANCE: Hyperintense foci on diffusion-weighted imaging (DWI) that are spatially remote from the acute hematoma occur in 20% of people with acute spontaneous intracerebral hemorrhage (ICH). Tranexamic acid, a hemostatic agent that is under investigation for treating acute ICH, might increase DWI hyperintense lesions (DWIHLs).

    OBJECTIVE: To establish whether tranexamic acid compared with placebo increased the prevalence or number of remote cerebral DWIHLs within 2 weeks of ICH onset.

    DESIGN, SETTING, AND PARTICIPANTS: This prospective nested magnetic resonance imaging (MRI) substudy of a randomized clinical trial (RCT) recruited participants from the multicenter, double-blind, placebo-controlled, phase 3 RCT (Tranexamic Acid for Hyperacute Primary Intracerebral Hemorrhage [TICH-2]) from July 1, 2015, to September 30, 2017, and conducted follow-up to 90 days after participants were randomized to either the tranexamic acid or placebo group. Participants had acute spontaneous ICH and included TICH-2 participants who provided consent to undergo additional MRI scans for the MRI substudy and those who had clinical MRI data that were compatible with the brain MRI protocol of the substudy. Data analyses were performed on an intention-to-treat basis on January 20, 2020.

    INTERVENTIONS: The tranexamic acid group received 1 g in 100-mL intravenous bolus loading dose, followed by 1 g in 250-mL infusion within 8 hours of ICH onset. The placebo group received 0.9% saline within 8 hours of ICH onset. Brain MRI scans, including DWI, were performed within 2 weeks.

    MAIN OUTCOMES AND MEASURES: Prevalence and number of remote DWIHLs were compared between the treatment groups using binary logistic regression adjusted for baseline covariates.

    RESULTS: A total of 219 participants (mean [SD] age, 65.1 [13.8] years; 126 men [57.5%]) who had brain MRI data were included. Of these participants, 96 (43.8%) were randomized to receive tranexamic acid and 123 (56.2%) were randomized to receive placebo. No baseline differences in demographic characteristics and clinical or imaging features were found between the groups. There was no increase for the tranexamic acid group compared with the placebo group in DWIHL prevalence (20 of 96 [20.8%] vs 28 of 123 [22.8%]; odds ratio [OR], 0.71; 95% CI, 0.33-1.53; P = .39) or mean (SD) number of DWIHLs (1.75 [1.45] vs 1.81 [1.71]; mean difference [MD], -0.08; 95% CI, -0.36 to 0.20; P = .59). In an exploratory analysis, participants who were randomized within 3 hours of ICH onset or those with chronic infarcts appeared less likely to have DWIHLs if they received tranexamic acid. Participants with probable cerebral amyloid angiopathy appeared more likely to have DWIHLs if they received tranexamic acid.

    CONCLUSIONS AND RELEVANCE: This substudy of an RCT found no evidence of increased prevalence or number of remote DWIHLs after tranexamic acid treatment in acute ICH. These findings provide reassurance for ongoing and future trials that tranexamic acid for acute ICH is unlikely to induce cerebral ischemic events.

    TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN93732214.

    Matched MeSH terms: Double-Blind Method
  18. Conlon B, Hamilton C, Meade E, Leong SL, O Connor C, Langguth B, et al.
    Sci Rep, 2022 Jun 30;12(1):10845.
    PMID: 35773272 DOI: 10.1038/s41598-022-13875-x
    More than 10% of the population suffers from tinnitus, which is a phantom auditory condition that is coded within the brain. A new neuromodulation approach to treat tinnitus has emerged that combines sound with electrical stimulation of somatosensory pathways, supported by multiple animal studies demonstrating that bimodal stimulation can elicit extensive neural plasticity within the auditory brain. More recently, in a large-scale clinical trial, bimodal neuromodulation combining sound and tongue stimulation drove significant reductions in tinnitus symptom severity during the first 6 weeks of treatment, followed by diminishing improvements during the second 6 weeks of treatment. The primary objective of the large-scale randomized and double-blinded study presented in this paper was to determine if background wideband noise as used in the previous clinical trial was necessary for bimodal treatment efficacy. An additional objective was to determine if adjusting the parameter settings after 6 weeks of treatment could overcome treatment habituation effects observed in the previous study. The primary endpoint at 6-weeks involved within-arm and between-arm comparisons for two treatment arms with different bimodal neuromodulation settings based on two widely used and validated outcome instruments, Tinnitus Handicap Inventory and Tinnitus Functional Index. Both treatment arms exhibited a statistically significant reduction in tinnitus symptoms during the first 6-weeks, which was further reduced significantly during the second 6-weeks by changing the parameter settings (Cohen's d effect size for full treatment period per arm and outcome measure ranged from - 0.7 to - 1.4). There were no significant differences between arms, in which tongue stimulation combined with only pure tones and without background wideband noise was sufficient to reduce tinnitus symptoms. These therapeutic effects were sustained up to 12 months after the treatment ended. The study included two additional exploratory arms, including one arm that presented only sound stimuli during the first 6 weeks of treatment and bimodal stimulation in the second 6 weeks of treatment. This arm revealed the criticality of combining tongue stimulation with sound for treatment efficacy. Overall, there were no treatment-related serious adverse events and a high compliance rate (83.8%) with 70.3% of participants indicating benefit. The discovery that adjusting stimulation parameters overcomes previously observed treatment habituation can be used to drive greater therapeutic effects and opens up new opportunities for optimizing stimuli and enhancing clinical outcomes for tinnitus patients with bimodal neuromodulation.
    Matched MeSH terms: Double-Blind Method
  19. Bustam A, Poh K, Zambri A, Mohd Nazri MZA, Subramaniam T, Abdullah AA, et al.
    Eur J Emerg Med, 2023 Oct 01;30(5):331-340.
    PMID: 37276052 DOI: 10.1097/MEJ.0000000000001047
    BACKGROUND AND IMPORTANCE: Musculoskeletal trauma is a common presentation in the emergency department (ED). Tramadol as an analgesic has been recommended by pain management guidelines for musculoskeletal pain. Parenteral tramadol in the ED is commonly administered intravenously. Subcutaneously administered tramadol may have other advantages such as easier and faster preparation, avoids the need for intravenous (i.v.) access, and reduces the incidence of respiratory and gastrointestinal effects. However, studies comparing subcutaneous (s.c.) and i.v. tramadol for the management of acute moderate pain in patients with extremity injury are lacking.

    OBJECTIVE: The objective of this study was to compare the clinical efficacy of s.c. tramadol vs. i.v. tramadol in patients with moderate pain due to extremity injury in the ED.

    DESIGN, SETTINGS, AND PARTICIPANTS: This non-inferiority randomized controlled trial included adult patients presented to an academic, tertiary hospital ED with moderate pain (pain score of 4-6 on the visual analog scale) due to extremity injury. Intervention patients stratified to pain score were randomized to receive 50 mg of i.v. or s.c. tramadol.

    OUTCOMES MEASURE AND ANALYSIS: Primary outcome measure was the difference in the pain score reduction at 30 min after tramadol administration between the two groups. The noninferiority null hypothesis was that the therapeutic difference in terms of pain score reduction of more than 0.8 exists between the two treatment groups at the endpoint.

    MAIN RESULTS: In total 232 patients were randomized to i.v. ( n  = 115) or s.c. ( n  = 117). Although 225 were analyzed in the per-protocol population (i.v. = 113; s.c. = 112). The baseline median pain score was 6 (IQR, 5-6). Median pain score reduction at 30 min after administration was 2 (IQR, 1-3) in the IV group vs. 2 (IQR, 1-2) in the s.c. group with a median difference of 0 (IQR, 0-0), which was below the prespecified noninferiority margin of 0.8. Adverse events in the i.v. group were higher compared to the s.c. group (33.6% vs. 8.9%, P  ≤ 0.001).

    CONCLUSIONS: The s.c. tramadol is noninferior to i.v. tramadol in the treatment of moderate pain from extremity injuries.

    Matched MeSH terms: Double-Blind Method
  20. Ang XY, Roslan NS, Ahmad N, Yusof SM, Abdullah N, Nik Ab Rahman NN, et al.
    Benef Microbes, 2023 Nov 23;14(5):421-431.
    PMID: 38350486 DOI: 10.1163/18762891-20220103
    The development of probiotics has now included the areas along the gut-vaginal axis. We thus aimed to investigate the effects of lactobacilli probiotic to modulate and restore vaginal and gut microbiota of pregnant women with vaginal candidiasis (VC). A randomised, double-blind and placebo-controlled study was performed in 78 pregnant women with VC. Patients were randomised to either the probiotic (SynForU-HerCare) or placebo which were administered at baseline and continued for 8-weeks (two capsules/day of 9.5 log cfu/capsule). Microbiota profiles were assessed at time points of weeks-0, 4 and 8 for high vaginal swab and faecal samples. Shannon diversity index showed that after 8-weeks amid VC, a shift in microbial community compositional changes occurred in the high vaginal region at both genus (P=0.025) and species (P=0.044) levels, where the administration of probiotic prevented such a shift. These changes were mainly attributed to a decreased in abundance of Lactobacillus (P=0.042) accompanied by increased abundance of Prevotella (P=0.002) and Atopobium (P=0.002) in the placebo group while the probiotic group remained unchanged over time. The administration of probiotics also prevented a reduced abundance of faecal phylum Firmicutes after 8-weeks as seen in the placebo group (P<0.0001), which also showed reduction at subsequent taxonomic levels of class, family, genera and species. VC has not only altered the microbiota of vagina regions but also gut microbiota profiles, causing lessening of gut microbiota that are crucial for gut nutrient availability, protection and immunity. The administration of lactobacilli probiotics has prevented such a shift, leading to better modulated gut and vaginal microenvironment amid VC. The study was registered at ClinicalTrials.gov: identifier number NCT03940612.
    Matched MeSH terms: Double-Blind Method
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