Double-blind Study Research Articles

Blinded Ex-Vivo testing in AML Reveals Differences between Hypomethylating Agents When Combined with Venetoclax

Introduction The therapeutic strategy of combining the hypomethylating agents (HMAs) Azacitidine (Aza) and Decitabine (Deci) with the BCL-2 inhibitor Venetoclax (Ven) has significantly improved the clinical outcomes of patients with Acute Myeloid Leukemia (AML), reaching overall response rates of up to 70% in clinical trials (Wei et al, JCO 2021). Still, on an individual basis, clinicians struggle to predict which patients will respond to Ven/HMA treatment. Furthermore, there is little data to guide selection of which HMA to use and the decision is generally based on physician preference and logistics. Functional ex-vivo testing using patient-derived primary cells has emerged as a promising approach to guide clinical decision (Letai et al, Cancer Cell 2022). This is particularly relevant for heme malignancies, given the ease of access to patient-derived cells from peripheral blood and/or bone marrow. We conducted a blinded study using OncoPrecision's proprietary Patient Micro-Avatars (PMAs) to predict clinical responses to Ven/HMA treatment. Methods De-identified diagnostic bone marrow aspirate samples from the leukemia program biobank at Weill Cornell Medicine that received Ven/HMA were provided to OncoPrecision for ex-vivo testing without information about the specific HMA used for treatment nor clinical response. PMAs are based on a triple co-culture platform that, by promoting the long term ex-vivo survival of Patient-Derived Cells (PDCs), allows testing the performance of different treatments. PDCs are co-cultured with two types of heterologous engineered cells: i) bone marrow stroma cells that act as a feed layer and as a control of non-specific toxicity (Tox-Control) and ii) a known outcome AML cell line that serves as an internal control of the system robustness and reproducibility in the response to drugs (System-Control). PMAs also leverage a multi-tagging approach coupled to high-throughput flow cytometry to track the differential response to treatments in subpopulations of pathological and healthy cells from each patient. This technology previously showed robust predictive power in observational studies in AML (García et al, Blood - 2022 ; Andino et al, Blood - 2023). Results PMAs were used to screen 39 AML patients who were treated with either Aza+Ven or Deci+Ven and from whom bone marrow or peripheral blood samples were stored prior to the start of treatment. OncoPrecision blindly tested these samples ex-vivo against a full dose-response curve of Aza+Ven and used their machine learning algorithm to predict clinical outcomes. When the predictions were matched against the clinical outcomes of the 27 patients of the cohort that received Aza+Ven at the clinic, the predictive accuracy (85%) was similar to the one previously reported in OncoPrecision's observational study (80%). Remarkably, however, when Aza+Ven predictions were matched to the clinical outcomes of the 12 patients in the cohort who received Deci+Ven, the predictive accuracy dropped to 50%. Interestingly, such a dramatic drop in the predictive power cannot be explained by a decrease in the negative predictive value (which remained >80%), but rather to a subpar positive predictive value (<30%), thus indicating that Aza may clinically outperform Deci in several of these patients. It is clear that ex-vivo testing using PMAs may have the ability to discern treatment sensitivity between Aza vs. Deci, and that there is potential to utilize this technology to tailor Ven/HMA therapy for individual patients. This is valuable not only to maximize potential disease response in a patient, but to also better prioritize patient quality of life during treatment, considering that Aza more commonly causes adverse effects like nausea and constipation than Deci. Conclusions Ex-vivo testing using PMAs has the potential to identify patients likely to respond to Ven/HMA and to discern treatment sensitivity between Aza vs. Deci. Our findings suggest that Aza and Deci may not always have equivalent efficacy for patients. This variation between Aza and Deci merits further exploration, especially since the therapeutic landscape for AML is likely to further expand with additional HMAs.

Efficacy Comparison of Ibuprofen 400 Mg and 800 mg in the Treatment of Renal Colic: Prospective Randomized Double-blind Clinical Study

Efficacy Comparison of Ibuprofen 400 Mg and 800 mg in the Treatment of Renal Colic: Prospective Randomized Double-blind Clinical Study

Effects of Toothpaste Containing 2% Zinc Citrate on Gingival Health and Three Related Bacteria-A Randomized Double-Blind Study.

Gingivitis is the initial stage of periodontitis, one of the most common oral diseases and the primary cause of tooth loss. This study aims to evaluate the effect of toothpaste containing 2% zinc citrate on gingival health and the abundance of three bacteria related to gingivitis and periodontitis. Eleven volunteers with the same oral health status were randomly assigned to the treatment (n = 5) and control (n = 6) groups. The control group used fluoride toothpaste, while the treatment group used fluoride toothpaste supplemented with 2% zinc citrate for 3 months. The plaque index, gingival index, and bleeding index were measured at baseline (0 day), 3 weeks, and 3 months. Dental plaque from four areas of the mouth (FDI criteria) was collected at the same timepoints. A total of 132 dental plaque samples were analyzed using quantitative PCR (qPCR) to monitor the abundance of Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, and Tannerella forsythia. Toothpaste containing 2% zinc citrate significantly lowered the gingival index and reduced gum bleeding but did not affect the plaque index. It also reduced the total abundance of the three bacteria related to gingivitis and periodontitis in dental plaque over a long-term period. Toothpaste with 2% zinc citrate persistently improves gingival health and reduces the presence of gingivitis-associated bacteria in dental plaque. Chinese Clinical Trial Registry (Clinical trial registration no.: ChiCTR1900020592) (09/01/2019).

Assessment of Treatment Response in Known Crohn's Disease-A Prospective Blinded Study Comparing the Diagnostic Accuracy of Intestinal Ultrasound, Magnetic Resonance Enterocolonography, Panenteric Capsule Endoscopy, and Fecal Calprotectin.

Minimally invasive modalities may replace ileocolonoscopy (IC) in the follow-up of Crohn's disease (CD). The aim of this study was to evaluate intestinal ultrasound (IUS), magnetic resonance enterocolonography (MREC), panenteric capsule endoscopy (PCE), and fecal calprotectin (FC) for determining response to medical treatment in patients with ileocolonic CD. This prospective, blinded, multicenter study included patients with endoscopically active CD. Patients were scheduled for IC, MREC, IUS, PCE, and FC before and 12 weeks after treatment with corticosteroids or biological therapy. A ≥50% reduction of the Simple Endoscopic Score for Crohn's Disease (SES-CD) with IC defined treatment response. Fifty patients completed the pre- and posttreatment evaluation with IC, and endoscopic response was achieved in 25 (50.0%). PCE was omitted in 12 (24.0%) patients because of stricturing CD. All activity scores decreased in patients achieving endoscopic response: The Simple Ultrasound Score for Crohn's Disease 2.2 vs 6.1 (P < .001), Magnetic Resonance Index of Activity 29.0 vs 37.1 (P = .05), SES-CD with PCE 3.1 vs 12.8 (P < .001), and FC 115.3 vs 1339.9mg/kg (P < .001). The sensitivity and specificity of IUS, MREC, PCE, and FC were 80.0% (95% CI, 56.3-94.3)/77.8% (95% CI, 52.4-93.6), 65.2% (95% CI, 42.7-83.6)/87.0% (95% CI, 66.4-97.2), 87.5% (95% CI, 61.7-98.4)/86.7% (95% CI, 59.5-98.3), and 90.0% (95% CI, 68.3-98.8)/86.4% (95% CI, 65.1-97.1), respectively. IUS and FC are equally effective for determining treatment response in patients with active CD. PCE is limited by the occurrence of strictures in this group of patients.

The missed chapter on midfoot: Chopart injuries.

Midtarsal injuries are often missed at initial presentation which may lead to long-term complications. Nonetheless, radiographs (XR) are used as a primary imaging method. The place of cone beam computer tomography (CBCT) remains unclear in the management of midfoot injuries. The aim of this study was to update imaging findings on traumatic ankle and foot injuries (TAAFI) with CBCT and to assess the sensitivity, specificity and accuracy of XR compared to CBCT for midfoot injuries detections. All CBCT studies performed due to (TAAFI) that had previous XR were collected for a period of 5years. They were retrospectively anonymized and analyzed by a radiologist. A second blinded study of XR was made by a second radiologist as a control. A total of 754 cases were included. Lisfranc and Chopart injuries were detected in 153 (20.2%) and 154 (20.4%) patients, respectively. Lisfranc and Chopart's lesions combined together were seen in 33 cases (10.7%). A blinded retrospective analysis of XR compared to CBCT shows a sensitivity of 64.9% (56.8-72.4%; 95% CI), a specificity of 95.0% (92.9-96.6%; 95% CI) and an accuracy of 88.9% (86.4-91.0%; 95% CI) for Chopart's injuries. Regarding Lisfranc, the sensitivity was 62.1% (53.9-69.8%; 95% CI), specificity 99.0% (97.8-99.6%; 95% CI) and accuracy 91.5% (89.3-93.4%; 95% CI). This cohort study highlights the missed injuries of Chopart on XR and the low association with Lisfranc avulsions. The use of CBCT helps in detecting and assessing midfoot injury.

Counterfactual Diffusion Models for Mechanistic Explainability of Artificial Intelligence Models in Pathology.

Deep learning can extract predictive and prognostic biomarkers from histopathology whole slide images, but its interpretability remains elusive. We develop and validate MoPaDi (Morphing histoPathology Diffusion), which generates counterfactual mechanistic explanations. MoPaDi uses diffusion autoencoders to manipulate pathology image patches and flip their biomarker status by changing the morphology. Importantly, MoPaDi includes multiple instance learning for weakly supervised problems. We validate our method on four datasets classifying tissue types, cancer types within different organs, center of slide origin, and a biomarker - microsatellite instability. Counterfactual transitions were evaluated through pathologists' user studies and quantitative cell analysis. MoPaDi achieves excellent image reconstruction quality (multiscale structural similarity index measure 0.966-0.992) and good classification performance (AUCs 0.76-0.98). In a blinded user study for tissue-type counterfactuals, counterfactual images were realistic (63.3-73.3% of original images identified correctly). For other tasks, pathologists identified meaningful morphological features from counterfactual images. Overall, MoPaDi generates realistic counterfactual explanations that reveal key morphological features driving deep learning model predictions in histopathology, improving interpretability.

Esketamine administered epidurally as an adjuvant to epidural ropivacaine for labour analgesia: a prospective, double-blind dose-response study.

To investigate the efficacy of esketamine as an adjuvant to epidural ropivacaine for labour analgesia by determining its effect on the median effective concentration (EC50) in a 20 ml volume of ropivacaine. A prospective, double-blind dose-response study. This study was conducted in Women's Hospital, School of Medicine, Zhejiang University, China. One hundred and fifty parturients who requested epidural analgesia were recruited in this study to randomly receive epidural ropivacaine alone or with esketamine of 0.2 mg ml-1, 0.3 mg ml-1, 0.4 mg ml-1 or 0.5 mg ml-1, respectively. The primary outcome, EC50 of ropivacaine, was determined using an up-down sequential allocation technique. The secondary outcomes were analgesia characteristics, Ramsay Sedation Scale score, labour duration, caesarean section rate and adverse effects. The EC50 of ropivacaine with the addition of esketamine at concentrations of 0.3 mg ml-1, 0.4 mg ml-1 and 0.5 mg ml-1 resulted in significant reductions in the EC50 of ropivacaine to 0.050%, 0.044% and 0.043%, respectively, from baseline (esketamine 0 mg ml-1) (p<0.0001). However, reductions of the EC50 of ropivacaine were similar among the groups with esketamine of 0.3 mg ml-1, 0.4 mg ml-1 and 0.5 mg ml-1 (p>0.05). The Ramsay Sedation Scale score was higher and more dizziness was observed in the Group of esketamine 0.5 mg ml-1 compared with all other groups (p<0.0001). During the peripartum period, no differences in sensory blockade level, Bromage score, labour duration and percentage of caesarean delivery were found among the groups. Under the conditions of this study, the addition of epidural esketamine of 0.3 mg⋅mL-1, 0.4 mg⋅mL-1 and 0.5 mg⋅mL-1 offered a similar ropivacaine dose-sparing effect; 0.5 mg⋅mL-1 of esketamine produced more adverse effects. ChiCTR2100054348.

Bimekizumab efficacy and safety in Korean patients with moderate to severe plaque psoriasis: A phase 3, randomized, placebo-controlled, double-blinded study.

Bimekizumab treatment has demonstrated significant improvements in clinical outcomes in patients with moderate to severe plaque psoriasis; however, studies so far have focused on predominantly White patient populations from North America and Europe, with one smaller study in a Japanese population. Here, clinical responses, safety, and tolerability of bimekizumab treatment in Korean patients are reported. Korean patients with moderate to severe plaque psoriasis were randomized to bimekizumab 320 mg every 4 weeks (Q4W) or placebo Q4W to week 16. Co-primary efficacy end points were achievement of ≥90% improvement from baseline in the Psoriasis Area and Severity Index (PASI 90) and Investigator's Global Assessment score of 0/1 (clear/almost clear) at week 16. Secondary efficacy end points included achievement of PASI 75 at week 4 and Dermatology Life Quality Index 0/1 at week 16. Safety outcomes were also assessed. Statistical analysis of the co-primary efficacy end points was performed using a type I error rate, at a two-sided α level of 0.05. Overall, 47 Korean patients were randomized to treatment (bimekizumab: 32, placebo: 15). At week 16, bimekizumab-treated patients had significantly higher clinical responses versus placebo-treated patients (PASI 90: 81.3% vs. 0%; IGA 0/1: 87.5% vs. 0%, p < 0.001 for both). Bimekizumab showed a rapid onset of clinical response, with 75.0% of patients achieving PASI 75 by week 4 (0% in placebo patients [nominal p < 0.001]). A higher proportion of bimekizumab-treated patients achieved DLQI 0/1 at week 16 (46.9% vs. 6.7% in placebo patients, nominal p = 0.007), indicating greater improvements in health-related quality of life (HRQoL) following bimekizumab treatment. Bimekizumab was well-tolerated in Korean patients, with no new safety signals identified. Treatment with bimekizumab led to rapid improvements in clinical responses and HRQoL versus placebo in Korean patients, consistent with responses in global populations. These findings suggest that bimekizumab is an effective and well-tolerated treatment option in Korean patients with psoriasis.

A double-blind pilot study of oral baricitinib in adult patients with lupus erythematosus panniculitis.

Lupus erythematosus panniculitis (LEP) is a chronic inflammatory skin disease with a significant impact on the overall well-being of patients. The safety and efficacy of oral baricitinib for the treatment of LEP have not been studied. This study aimed to explore the efficacy of oral baricitinib in patients with LEP who are recalcitrant or intolerant to conventional therapies. Patients (aged ≥18 years) with active LEP (with a revised cutaneous lupus erythematosus disease area and severity index [RCLASI]-active score ≥4] were randomly assigned 2:1 to baricitinib (4 mg) or placebo (once daily for 20 weeks). The placebo group was switched to baricitinib (4 mg) at week 13, and the final evaluation was conducted at week 24. The primary endpoint was the proportion of patients with an RCLASI-A score decreased by 20% at week 12. The secondary endpoints included the changes in the Cutaneous Lupus Erythematosus Disease Area and Severity Index active-(CLASI-A) score, the Dermatology Life Quality Index (DLQI), the Physician's Global Assessment (PGA) score, and safety. Five patients were enrolled. Three patients received baricitinib (4 mg), and two patients were treated with placebo. Two patients in the baricitinib treatment group showed a significant RCLASI-A decrease at week 12 and week 24. Two patients in the placebo group had no change in RCLASI-A at week 12 and a significant decrease at week 24. No new safety events were observed. Treatment with baricitinib was effective and well tolerated in patients with LEP.

Experience with reduced-nicotine cigarettes and whether this decreases smoking and substitution for full-nicotine cigarettes.

Studies suggest that reduced-nicotine cigarettes decrease nicotine intake and dependence. However, questions remain about reduced-nicotine cigarette abuse liability, whether reduced-nicotine cigarette exposure lowers reduced- and full-nicotine cigarette use, and whether reduced-nicotine cigarettes substitute for full-nicotine cigarettes. This randomized, double-blind laboratory study used operant behavioral economics to examine abuse liability of cigarettes with varying nicotine content. Non-treatment-seeking smokers (N = 43) self-administered reduced- (5.2, 2.4, or 1.3 mg/g) and full-nicotine (15.8 mg/g) cigarettes before and after 3 weeks of at-home exposure. Participants were randomized to full-nicotine or one of the reduced-nicotine cigarettes to determine the effect of exposure on abuse liability and substitutability. Abuse liability was assessed in single-commodity sessions, and substitutability was measured in concurrent-commodity sessions. In the self-administration sessions, concurrently available reduced-nicotine cigarettes attenuated full-nicotine cigarette demand and rendered reduced-nicotine cigarettes partial substitutes for full-nicotine cigarettes. Exposure to study cigarettes for 3 weeks marginally reduced demand for reduced- and full-nicotine cigarettes irrespective of nicotine content. Results suggest a limited influence of nicotine content on smoking behavior in established smokers and highlight the role of nonpharmacological factors (e.g., taste/smell) on the maintenance of smoking. These results should be considered in determining whether a nicotine-reduction standard is a feasible path for reducing cigarette demand.

The comparison of efficacy of Escitalopram and Bupropion in treatment of depression symptoms in patients with heart failure: randomized clinical trial.

This study aims to compare the effects of two medicines, Escitalopram and Bupropion, on HF patients who have depression symptoms. This double-blind randomized clinical trial study was conducted on HF patients with depression symptoms at the Heart Failure Clinics affiliated with Babol University of Medical Sciences. In this study, 80 participants were examined for depression based on the Beck Depression Inventory (BDI) and Hamilton Depression Rating Scale (HDRS). They were randomly allocated into two groups of 40 participants treated with Bupropion 75mg and Escitalopram 5mg. Following the intervention, the individuals were assessed in terms of their depression score at 4, 8, and 12-week intervals. Finally, the data were analyzed using SPSS version 22.0. In the examination of Beck and Hamilton scores in the two research groups during different follow-ups, a significant decrease was found over time (P<0.001 for both medicines). While the effectiveness of the two medicines was the same at different times (P>0.05 in all cases). Comparing the side effects between the two intervention groups, the orgasm disorder (P=0.018) and sexual dysfunction (P<0.001) were reported significantly more in the Escitalopram group than in the Bupropion group. The findings of this study showed that Escitalopram has the same efficacy as Bupropion in the treatment of depression symptoms in HF patients.

Development of and recovery from acute kidney injury after cardiac surgery: Randomized phase 2 trial of the hepatocyte growth factor mimetic ANG-3777

To investigate the safety and efficacy of ANG-3777, a hepatocyte growth factor mimetic, in mitigating the risk of acute kidney injury (AKI) in patients undergoing cardiac surgery with cardiopulmonary bypass. In this double-blind placebo-controlled study (GUARD), patients were randomized to receive intravenous ANG-3777 2 mg/kg or placebo once daily for 4 days. The primary endpoint was AKI severity, measured by mean area under the concentration-time curve on percent increase in serum creatinine from days 2 to 6. Secondary endpoints included the proportions of patients who developed major adverse kidney events by day 30 or 90 and the percentage of patients diagnosed with AKI through day 5. In total, 259 patients received study treatment (ANG-3777, n = 129; placebo, n = 130). Through day 6, there was no significant difference in least-squares mean change in serum creatinine between ANG-3777 and placebo (1.1%; 95% CI, -6.2, 8.4; P = .77), or in proportions of patients who developed major adverse kidney events by day 30 (18.6% vs 16.2%; P = .60) or day 90 (14.7% vs 21.5%; P = .16). Similar proportions of patients were diagnosed with AKI through day 5 (ANG-3777, 47.3%; placebo, 48.5%); however, exploratory analysis revealed more patients diagnosed with AKI postoperatively showed signs of recovery following treatment with ANG-3777 than placebo. Overall, ANG-3777 was well tolerated, with similar incidences of treatment-emergent adverse events between treatment arms. Findings from this study do not support the efficacy of ANG-3777 in preventing the development of AKI following cardiopulmonary bypass.

Efficacy and Safety of Biosimilar Cetuximab Versus Innovator Cetuximab in Indian Patients With Head and Neck Cancer: A Multicenter, Randomized, Double-Blind, Phase III Trial.

Squamous cell carcinoma of the head and neck (SCCHN) is the sixth most common cancer, with approximately 225,419 new cases with over 125,000 deaths annually in India. This trial compared the efficacy and safety of biosimilar cetuximab versus innovator cetuximab (IC) in combination with platinum-based chemotherapy in patients with recurrent locoregional or metastatic SCCHN. This phase III trial is a multicenter, randomized, double-blind and parallel group study performed in Indian patients with recurrent locoregional or metastatic SCCHN. Patients were randomly assigned in 2:1 ratio to receive biosimilar cetuximab and IC in combination with cisplatin and fluorouracil via intravenous infusions. The primary end points were disease control rate (DCR) and overall response rate (ORR) as per response evaluation criteria in solid tumors version 1.1. The secondary end points included pharmacokinetics (PK), immunogenicity, safety, and tolerability. Of 180 patients enrolled, 120 patients received biosimilar cetuximab and 60 patients received IC treatment. No significant statistical difference was observed in the primary outcomes between two groups. Treatment difference in DCR and ORR response was found to be -5.21 (90% CI, -8.94 to -1.48) and -4.79 (90% CI, -19.42 to 9.84), respectively, indicating noninferiority to reference product. The incidence of treatment-emergent adverse events (AEs; biosimilar cetuximab: 89.2% v IC: 91.7%; P = .8364) and serious AEs (biosimilar cetuximab: 23.3% v IC: 13.3%; P = .0603) and PK parameters were comparable between treatment groups. The immunogenicity findings showed higher incidence of anticetuximab antibodies in the biosimilar cetuximab group compared with the IC group at the end of Study. The findings of this study demonstrated noninferiority along with comparable PK, safety, and immunogenicity of biosimilar cetuximab and IC in patients with recurrent or metastatic SCCHN.

Plate or Arthroplasty for complex Mason Type-III Radial Head Fractures? Mid-to-long term results from a blinded outcome assessor study

BackgroundThe surgical treatment of radial head fractures like Mason type III comminuted radial head fractures is challenging and controversial. Whether to use open reduction and internal fixation (ORIF) or radial head arthroplasty (RHA) as treatment methods is under constant debate. MethodsWe retrospectively analyzed clinical and radiographic mid- to long-term results of 42 patients with a mean follow-up time of 4.56 years (1.92-7.58 years). Patients were grouped according to fragment numbers and the type of intervention performed (3-4 fragments vs. 4+ fragments; ORIF vs. RHA). At the final follow-up, range of motion (ROM), functional rating scores and subjective pain and function levels were documented by a blinded outcome assessor. ResultsAlthough minor differences in the mean values were detected when comparing the results of the functional scores, ROM and subjective pain and function levels, only the movement in pronation and supination direction yielded statistically better results in the group of 4+-fragments for the RHA compared to ORIF. However, the 33% rate of required implant removal amongst the ORIF group should be considered. ConclusionsThis study provides evidence that 3- and 4-part Mason type III fractures are prone to plate osteosynthesis. In contrast, greater than 4-part fractures can more reliably be treated by replacement. This leads to a proposed increase in fragment numbers to four, where ORIF most likely leads to good clinical results. However, in patients with 4+ fragment patterns, ORIF did not show statistically significantly worse results concerning the collected clinical values. This study supports the use of the ORIF approach to save the radial head.

Tacrolimus versus hydrocortisone in management of atopic dermatitis in children, a randomized controlled double-blind study: New insights on TARC, CTACK, TSLP, and E-selectin.

Atopic dermatitis (AD) is a type of chronic inflammatory disorder that affects all age groups including children. AD is characterized by elevated inflammatory marker levels. To assess the safety and effectiveness of topical tacrolimus ointment versus topical hydrocortisone cream in the treatment of pediatric AD by comparing the two treatments' ability to reduce serum cytokines. One hundred AD patients who fulfilled the eligibility criteria completed this clinical study. Two groups of 50 AD patients each were selected from Tanta University's Dermatology Department., Group 1 (the hydrocortisone group) was administered topical hydrocortisone cream for a duration of 4 months. For 4 months, Group 2 was administered tacrolimus topically. Serum levels of thymus and activation regulated chemokine (TARC), cutaneous T cell attractant chemokine (CTAC), interleukin-10 (IL-10), interleukin-6 (IL-6), E selectin (E-selectin), and thymic stromal lymphopoietin (TSLP) were measured during an evaluation of the patients by a dermatologist at the beginning and 4 months after the treatment had been started. Children's Dermatology Life Quality Index was used to assess quality of life in these patients. With the exception of E-selectin, IL-6, and IL-10 (p > .05), the tacrolimus group had a significant reduction in TARC, CTACK, TSLP (p < .05) when compared to its baseline and when compared to the hydrocortisone group. Both groups showed a significant improvement in quality of life but no significant changes between groups were observed. In children with AD, tacrolimus reduces inflammatory biomarkers better than hydrocortisone.

A Randomized Controlled Trial to Compare the Analgesic Efficacy of Ultrasound-Guided Fascia Iliaca Compartment Block and Femoral Nerve Block in Patients with Neck of Femur Fracture

ABSTRACT Background and Aims: Regional nerve blocks under ultrasound guidance have heralded the era toward safer anesthetic practices. They provide adequate analgesia during positioning for subarachnoid block in patients posted for hip. We aimed to compare the analgesic efficacy of fascia iliaca compartment block and femoral nerve block for pain during sitting position for subarachnoid block, duration of post-op analgesia, and document any complications. Material and Methods: A randomized double-blind study was conducted in 60 patients undergoing isolated neck of femur fracture surgery under subarachnoid block. They were randomized by a computer-generated randomization table into two groups – group A received a fascia iliaca compartment block and group B received a femoral nerve block. Numeric rating score (NRS) was noted before block, during positioning, and postoperatively for 24 hours. An independent sample t-test and a paired t-test were used for intergroup and intra-group comparisons. Results: The mean NRS before block in group A (7.57 ± 0.50) and group B (7.40 ± 0.49) (P-value = 0.203) was not significant. NRS during positioning in group A (2.10 ± 0.88) was significantly lower than group B (3.33 ± 0.71) (P-value = 0.001*). The mean NRS from the sixth till 20th hour postoperatively was significantly higher in group B compared to group A (P-value &lt;0.05 for all). The mean time to first rescue analgesia was significantly longer in group A (23.57 ± 2.22 hours) compared to group B (11.97 ± 1.73 hours) (P-value = 0.001*). No complications were noted during the study. Conclusion: Fascia iliaca compartment block gives significantly better pain relief during positioning for subarachnoid block and prolonged postoperative analgesia as compared to femoral nerve block.

Intravenous lidocaine reduces cough but not propofol dose during gastroscopy: a prospective, randomised controlled double-blind study

Intravenous lidocaine reduces cough but not propofol dose during gastroscopy: a prospective, randomised controlled double-blind study

Efficacy and Safety of Pemafibrate Extended-Release Tablet: a Phase 3, Multicenter, Randomized, Double-Blind, Active-Controlled, Parallel-Group Comparison Trial.

Pemafibrate, a selective peroxisome proliferator-activated receptor α modulator that lowers serum triglyceride levels and increases high-density lipoprotein cholesterol levels, is approved for treating dyslipidemia as twice-daily immediate-release (IR) tablets. A once-daily extended-release (XR) tablet has also been developed. We aimed to confirm the non-inferiority of XR (0.2 or 0.4 mg/day; once daily) to IR (0.2 mg/day; twice daily) in lowering triglyceride levels in patients with hypertriglyceridemia. This phase 3, multicenter, randomized, double-blind study included patients with fasting triglycerides ≥ 200 mg/dL who received IR (0.2 mg/day) or XR (0.2 or 0.4 mg/day). The primary efficacy endpoint was the percentage change in fasting triglyceride levels from baseline to 4, 8, and 12 weeks. Common treatment effects at weeks 4 through 12 were compared between groups using repeated analysis of covariance. In 356 randomized patients, fasting triglyceride levels decreased by 48.0%, 43.8%, and 48.0% with IR 0.2, XR 0.2, and XR 0.4 mg/day, respectively, confirming the non-inferiority of both XR regimens to IR. The proportion of patients who achieved fasting triglycerides ＜150 mg/dL was 45.7%, 37.4%, and 51.7%, while the percentage change of triglycerides in the subgroup with baseline triglycerides ≥ 500 mg/dL was -59.3%, -52.2%, and -66.3% with IR 0.2, XR 0.2, and XR 0.4 mg/day, respectively. XR (0.2 and 0.4 mg/day) was non-inferior to IR (0.2 mg/day). XR 0.4 mg/day demonstrated a more potent triglyceride-lowering effect than XR 0.2 mg/day and should be considered for patients with high triglyceride levels.

A phase II, randomized, double-blind study of the use of rucaparib versus placebo maintenance therapy in metastatic and recurrent endometrial cancer

A phase II, randomized, double-blind study of the use of rucaparib versus placebo maintenance therapy in metastatic and recurrent endometrial cancer

Effects of Small-Dose Esketamine on Postoperative Analgaesia and Sleep Quality in Patients with Total Hip Replacement.

To determine the effect of esketamine in patient-controlled analgaesia after hip replacement on postoperative pain and improve sleep quality in patients. Randomised double-blind study. Place and Duration of the Study: Department of Anaesthesiology, The First Affiliated Hospital of Guangxi Medical University, from March 2021 to May 2022. The research enrolled 72 patients who were subjected to unilateral complete hip replacement surgery utilising jointly administered universal and peripheral nerve-obstructing anaesthetics. A randomised numeric table method was used to allocate patients to either the F-D group (fentanyl combined with dexmedetomidine, n = 34) or the Es-D group (esketamine combined with dexmedetomidine, n = 38). The key outcome indicators included the time to first administration of rescue analgaesic, the dose of rescue analgaesics, and postoperative sleep quality. Baseline characteristics did not differ between the two groups. The time until postoperative analgaesic rescue medication was considerably shorter for those in the Es-D group (p <0.05). In addition, the Es-D group used significantly fewer rescue analgaesics (p = 0.01). The PSQI score and unpleasant responses (PONV, dizziness, nightmare) did not significantly differ between the two groups (p <0.05). Nevertheless, urine retention occurred in four patients in group F-D but not in group Es-D (p <0.05). Esketamine produced better analgaesia than fentanyl with fewer side effects after surgery. However, no improvement was observed in sleep quality. Arthroplasty, Postoperative analgaesia, Esketamine, Sleep quality, Patient-controlled analgaesia.