Primary Efficacy Measure Research Articles

Comparing two transitioning strategies to paliperidone palmitate once-every-6-months.

A double-blind, randomized, active-controlled, parallel-group, noninferiority trial (NCT03345342) demonstrated that paliperidone palmitate once-every-6-months (PP6M) was noninferior to paliperidone palmitate once-every-3-months (PP3M) in preventing relapse in clinically stable adults with schizophrenia. This post hoc analysis assessed efficacy and safety following transition to PP6M from paliperidone once-monthly (PP1M) versus PP3M. Adults with schizophrenia who were clinically stable on moderate/high doses of PP1M or PP3M were randomly assigned 1:2 to dorsogluteal PP3M or PP6M treatment for 12months. The primary efficacy measure was time to relapse during the 12-month DB phase. Secondary endpoints included change from DB baseline to endpoint in Positive and Negative Syndrome Scale (PANSS) total and subscale scores, Clinical Global Impression-Severity (CGI-S) scale score, and Personal and Social Performance (PSP) scale score. Safety was assessed by treatment-emergent adverse events (TEAEs), vital signs, and clinical laboratory tests. Of 702 patients in the study, 231 transitioned from PP1M to PP6M and 247 transitioned from PP3M to PP6M. Low relapse rates for PP6M were observed regardless of transition pathway (PP1M/PP6M: 7.8%; PP3M/PP6M: 7.3%). Changes from DB baseline to endpoint in PANSS total, PSP, and CGI-S scores were similar between transition groups. In the DB phase, ≥1 TEAE was observed in 61.0% and 63.2% of patients in the PP1M/PP6M and PP3M/PP6M, groups, respectively. Adults with schizophrenia who transitioned to PP6M from either PP1M or PP3M experienced similarly low relapse rates. Additionally, symptom and functionality scores supported the primary analysis and, along with TEAE incidences, were comparable between transition groups.

Sacral and Implantable Tibial Neuromodulation for the Management of Overactive Bladder: A Systematic Review and Meta-analysis.

Implantable tibial neuromodulation (iTNM) systems have recently become commercially available in the US, and offer a new method of neurostimulation for the treatment of overactive bladder (OAB). In the absence of head-to-head studies, the aim of this meta-analysis was to indirectly compare the efficacy and safety of sacral neuromodulation (SNM) and implantable tibial neuromodulation (iTNM) for the treatment of OAB. A comprehensive search was performed using terms for OAB and neuromodulation. Primary efficacy measures included a≥50% reduction in urgency urinary incontinence (UUI) episodes, urinary frequency, and/or OAB symptoms. Primary safety measures included the rate of device-related adverse events (AEs). A total of 20 studies met selection criteria, encompassing 1416 patients treated with SNM and 350 patients treated with iTNM. No comparative or placebo-controlled studies for SNM and iTNM were identified, and therefore the analysis was completed using single-arm results. Weighted averages showed that the UUI responder rate was similar for both SNM and iTNM (71.8% and 71.3%, respectively). Similarly, weighted averages of OAB responder rates were 73.9% for SNM and 79.4% for iTNM. Similar rates of device-related AEs were also observed. This meta-analysis found similar efficacy and safety of SNM and iTNM for the treatment of OAB and UUI, including UUI and OAB symptom response rates, reduction in UUI episodes, significant improvements in quality-of-life (QoL), and low rates of procedure and device-related adverse events. Notably, this comparable efficacy was seen without the use of a trial phase of neuromodulation in the iTNM studies versus SNM studies.

Combining Recurrent and Terminal Events Into a Composite Endpoint May Be Problematic

In clinical trials for chronic heart failure (CHF), time to a composite of first hospitalization for worsening heart failure or death is a widely accepted primary efficacy measure. Motivated by lower event rates in recent CHF trials, there are proposals to use endpoints accounting for recurrent heart failure hospitalization (HFH) events (e.g. recurrent HFH events plus death as an additional event) as the primary endpoint to better quantify disease burden and to improve trial efficiency. However, analysis and interpretation of recurrent event endpoints may be complicated by the terminal event death. In a previous simulation study it was shown that the type I error rate was well-controlled for the analysis of the composite recurrent event endpoint using the negative binomial (NB) model and the Lin-Wei-Yang-Ying (LWYY) model. As these results were based on limited scenarios, we extended the previous simulation study and identified situations where the type I error rate is no longer controlled for the analysis of the composite recurrent event endpoint using the LWYY model, despite a neutral effect on HFH and a detrimental effect on death of the experimental treatment. Therefore, depending on clinical settings, the LWYY model should be applied and interpreted with more caution.

Multichannel tDCS with advanced targeting for major depressive disorder: a tele-supervised at-home pilot study.

Proof-of-principle human studies suggest that transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex (DLPFC) may improve depression severity. This open-label multicenter study tested remotely supervised multichannel tDCS delivered at home in patients (N=35) with major depressive disorder (MDD). The primary aim was to assess the feasibility and safety of our protocol. As an exploratory aim, we evaluated therapeutic efficacy: the primary efficacy measure was the median percent change from baseline to the end of the 4-week post-treatment follow-up period in the observer-rated Montgomery-Asberg Depression Mood Rating Scale (MADRS). Participants received 37 at-home stimulation sessions (30 minutes each) of specifically designed multichannel tDCS targeting the left DLPFC administered over eight weeks (4 weeks of daily treatments plus 4 weeks of taper), with a follow-up period of 4 weeks following the final stimulation session. The stimulation montage (electrode positions and currents) was optimized by employing computational models of the electric field generated by multichannel tDCS using available structural data from a similar population (group optimization). Conducted entirely remotely, the study employed the MADRS for assessment at baseline, at weeks 4 and 8 during treatment, and at 4-week follow-up visits. 34 patients (85.3% women) with a mean age of 59 years, a diagnosis of MDD according to DSM-5 criteria, and a MADRS score ≥20 at the time of study enrolment completed all study visits. At baseline, the mean time since MDD diagnosis was 24.0 (SD 19.1) months. Concerning compliance, 85% of the participants (n=29) completed the complete course of 37 stimulation sessions at home, while 97% completed at least 36 sessions. No detrimental effects were observed, including suicidal ideation and/or behavior. The study observed a median MADRS score reduction of 64.5% (48.6, 72.4) 4 weeks post-treatment (Hedge's g = -3.1). We observed a response rate (≥ 50% improvement in MADRS scores) of 72.7% (n=24) from baseline to the last visit 4 weeks post-treatment. Secondary measures reflected similar improvements. These results suggest that remotely supervised and supported multichannel home-based tDCS is safe and feasible, and antidepressant efficacy motivates further appropriately controlled clinical studies. https://clinicaltrials.gov/study/NCT05205915?tab=results, identifier NCT05205915.

Efficacy and Safety of Lurasidone vs. Quetiapine XR in Acutely Psychotic Patients With Schizophrenia in Korea: A Randomized, Double-Blind, Active-Controlled Trial.

This study was performed to evaluate the efficacy and safety of lurasidone (160 mg/day) compared to quetiapine XR (QXR; 600 mg/day) in the treatment of acutely psychotic patients with schizophrenia. Patients were randomly assigned to 6 weeks of double-blind treatment with lurasidone 160 mg/day (n=105) or QXR 600 mg/day (n=105). Primary efficacy measure was the change from baseline to week 6 in Positive and Negative Syndrome Scale (PANSS) total score and Clinical Global Impressions severity (CGI-S) score. Adverse events, body measurements, and laboratory parameters were assessed. Lurasidone demonstrated non-inferiority to QXR on the PANSS total score. Adjusted mean±standard error change at week 6 on the PANSS total score was -26.42±2.02 and -27.33±2.01 in the lurasidone and QXR group, respectively. The mean difference score was -0.91 (95% confidence interval -6.35-4.53). The lurasidone group showed a greater reduction in PANSS total and negative subscale on week 1 and a greater reduction in end-point CGI-S score compared to the QXR group. Body weight, body mass index, and waist circumference in the lurasidone group were reduced, with significantly lower mean change compared to QXR. Endpoint changes in glucose, cholesterol, triglycerides, and low-density lipoprotein levels were also significantly lower. The most common adverse drug reactions with lurasidone were akathisia and nausea. Lurasidone 160 mg/day was found to be non-inferior to QXR 600 mg/day in the treatment of schizophrenia with comparable efficacy and tolerability. Adverse effects of lurasidone were generally tolerable, and beneficial effects on metabolic parameters can be expected.

A Comparative Analysis of Norepinephrine with Midodrine/Octreotide in Patients with Hepatorenal Syndrome-acute Kidney Injury

Background Hepatorenal Syndrome (HRS) is a severe complication of end-stage liver disease characterized by functional renal impairment. This study aimed to assess the efficacy of norepinephrine compared to midodrine/octreotide in managing patients diagnosed with hepatorenal syndrome type 1. Materials and Methods In this double-blind Randomized Clinical Trial, 50 patients with hepatorenal syndrome type 1 were randomly assigned to the norepinephrine and midodrine/octreotide groups. The norepinephrine group received an initial dose of 1 mg/h (up to a maximum of 4 mg/h) along with daily intravenous injections of 20% albumin (20-40 grams per day) throughout the study period. The control group received midodrine (maximum dose of 15 mg three times a day), octreotide (maximum dose of 200 micrograms intravenously three times a day), and 20 to 40 mg of 20% albumin daily. The primary efficacy measure was the percentage of patients achieving a complete response, defined by the restoration of serum creatinine levels to within 0.3 mg/dl of the baseline by the end of treatment. Results There was no significant difference in the rate of complete response between the norepinephrine group (7/25, 28%) and the midodrine/octreotide group (3/25, 12%) (p=0.15). The mortality rate was 10 (40%) in the norepinephrine group and 12 (48%) in the midodrine/octreotide group. Although the mortality rate was higher in the midodrine/octreotide group (12/25, 48%) compared to the norepinephrine group (10/25, 40%), this difference was not statistically significant (p=0.77). Conclusion The study findings suggest that the norepinephrine treatment regimen can be as effective as or more effective than the midodrine/octreotide regimen in treating hepatorenal syndrome in cirrhotic patients. Therefore, these two treatment regimens can be used interchangeably. Clinical Trial Registration Number IRCT20230228057568N1

Thromboelastography-Guided Antiplatelet Therapy for Patients with Ischemic Cerebrocardiovascular Diseases: A Systematic Review and Meta-Analysis.

The effectiveness of thromboelastography (TEG)-guided antiplatelet therapy in patients with ischemic cerebrocardiovascular diseases is not well-established. This systematic review evaluates the efficacy and safety of TEG-guided antiplatelet therapy compared to standard treatment in patients with ischemic cerebrocardiovascular diseases. Randomized controlled trials (RCTs) and observational studies comparing TEG-guided antiplatelet therapy with standard therapy in patients suffering from ischemic stroke (IS) or coronary artery disease (CAD) were identified. The primary efficacy measure was a composite of ischemic and hemorrhagic events. Secondary efficacy measures included any ischemic events, while safety was assessed by the occurrence of bleeding events. Ten studies involving 4 RCTs and 6 observational studies with a total of 1,678 patients were included. When considering a composite of ischemic and hemorrhagic events in RCTs, a significant reduction was observed in IS or CAD patients under TEG-guided therapy compared to standard therapy (OR: 0.45, 95% CI: 0.27-0.75, p = 0.002). After pooling RCTs and observational studies together, compared to standard antiplatelet therapy, TEG-guided therapy significantly reduced the risk of a composite of ischemic and hemorrhagic events (OR: 0.26, 95% CI: 0.19-0.37; p < 0.00001), ischemic events (OR: 0.28, 95% CI: 0.19-0.41; p < 0.00001), and bleeding events (OR: 0.31, 95% CI: 0.16-0.62; p = 0.0009) in patients with IS or CAD. TEG-guided antiplatelet therapy appears to be both effective and safe for patients with IS or CAD. These findings support the use of TEG testing to tailor antiplatelet therapy in individuals with ischemic cerebrocardiovascular diseases.

Effects of CYP3A4 genetic polymorphisms on the pharmacokinetics and efficacy of perampanel in Chinese pediatric patients with epilepsy

ObjectiveThis study was the first to evaluate the effect of CYP3A4 gene polymorphisms on the plasma concentration and effectiveness of perampanel (PER) in Chinese pediatric patients with epilepsy. MethodsWe enrolled 102 patients for this investigation. The steady-state concentration was determined after patients maintained a consistent PER dosing regimen for at least 21 days. Plasma PER concentrations were measured using liquid chromatography–tandem mass spectrometry. Leftover samples from standard therapeutic drug monitoring were allocated for genotyping analysis. The primary measure of efficacy was the rate of seizure reduction with PER treatment at the final check-up. ResultsThe CYP3A4×10 GC phenotype exhibited the highest average plasma concentration of PER at 491.1 ± 328.1 ng/mL, in contrast to the CC phenotype at 334.0 ± 161.1 ng/mL. The incidence of adverse events was most prominent in the CYP3A4×1 G TT and CYP3A4×10 GC groups, with rates of 77.8 % (7 of 9 patients) and 50.0 % (46 of 92 patients), respectively. Moreover, the percentage of patients for whom PER was deemed ineffective was least in the CYP3A4×1 G TT and CYP3A4×10 CC groups, recorded at 11.1 % (1 of 9 patients) and 10.0 % (1 of 10 patients), respectively. There was a significant correlation between PER plasma concentration and either exposure or toxicity (both with p < 0.05). We suggest a plasma concentration range of 625–900 ng/mL as a suitable reference for PER in Chinese patients with epilepsy. ConclusionThe CYP3A4×10 gene's genetic polymorphisms influence plasma concentrations of PER in Chinese pediatric patients with epilepsy. Given that both efficacy and potential toxicity are closely tied to plasma PER levels, the CYP3A4 genetic phenotype should be factored in when prescribing PER to patients with epilepsy.

Two-year Pivotal Study Analysis of the Safety and Efficacy of Implantable Tibial Nerve Stimulation With eCoin for Urgency Urinary Incontinence

ObjectiveTo evaluate the continued effectiveness and safety of the eCoin Implantable Tibial Nerve Stimulator system (ITNS) for urgency urinary incontinence in patients with overactive bladder.The one-year pivotal study was extended through two years. The ITNS is a novel and recently FDA-approved therapy. MethodsA prospective, multicenter, single-arm trial was conducted on 137 subjects with refractory urgency urinary incontinence to evaluate eCoin ITNS therapy. A 3-day voiding diary was collected along with the overactive bladder questionnaire, Patient Global Impression of Improvement, and a custom Likert scale on subject satisfaction. The primary efficacy measure was the proportion of subjects who achieved at least 50% reduction from baseline in number of urgency urinary incontinence episodes. The primary safety measure was device-related adverse events. Results72 subjects completed the 96-week evaluation. 78% (95% CI: 67% - 87%) experienced at least 50% reduction in urgency urinary incontinence episodes; 48% (95% CI, 36%-60%) experienced at least 75% reduction, and 22% (95% CI, 13%-33%) were dry on a 3-day diary. Subjects reported a decrease from baseline in their urgency urinary incontinence episodes/day of 2.61 (SD 2.97) and 2.97 (SD 2.64) at 48 weeks and 96 weeks, respectively. 91.3% did not require additional medications for overactive bladder. No serious or unanticipated adverse events were reported in this extension phase. ConclusionsThe eCoin ITNS demonstrated consistent continuing effectiveness and safety in treating overactive bladder patients with urgency urinary incontinence. The findings support it as an excellent treatment option for refractory patients.

A standardized combination of Terminalia chebula and Withania somnifera extracts enhances immune function in adults: a pilot randomized, double-blind, placebo-controlled clinical study.

The use of botanical medicine has been demonstrated as a potential strategy to manage or treat a variety of health issues. Terminalia chebula (Retz) fruit and Withania somnifera (L.) Dunal roots are important medicinal herbs described in Ayurveda and traditional therapy for diverse health benefits. This pilot study aimed to evaluate the immune function-enhancing potential of a unique blend of T. chebula fruit and W. somnifera root extracts, LN20189, in healthy men and women. Forty healthy volunteers (age: 35-60 years) were randomized into two groups receiving either LN20189 (500 mg per day) or a matched placebo over 28 consecutive days. The total T-cell population was the primary efficacy measure in this study. The secondary efficacy measures included counts of CD4, CD8, natural killer (NK) cells, serum levels of interleukin-2 (IL-2), interferon-gamma (IFN-γ), total immunoglobulin-G (IgG), and Immune Function Questionnaire (IFQ) scores. Safety parameter assessments were also conducted. Post-trial, in LN20189-supplemented subjects, T cells, CD4, NK cells count, and the CD4:CD8 ratio were increased by 9.32, 10.10, 19.91, and 17.43%, respectively, as compared to baseline. LN20189 supplementation increased serum IFN-γ and IgG levels by 14.57 and 27.09% from baseline and by 13.98 and 21.99%, compared to placebo, respectively. Also, the IFQ scores in the LN20189 group were 84.68% (vs. baseline) and 69.44% (vs. placebo) lower at the end of the trial. LN20189 improved the study volunteers' cellular and humoral immune functions. In summary, LN20189 supplementation was found tolerable and improved the key cellular and humoral factors of the immune system and helped improve immune function of the trial volunteers.

Боль в спине. Результаты неинтервенционного исследования применения препарата Амбениум® парентерал в условиях реальной клинической практики

Aim: to estimate efficacy, tolerability, and safety of Ambenium® parenteral [phenylbutazone sodium 400 mg and lidocaine hydrochloride 4 mg] used for treatment of patients with low back pain. Methods. A total of 100 patients with low back pain (LBP), who received a single intramuscular injection of Ambenium® parenteral, were included in the study. The follow-up period was 3 days. The change in pain severity on VAS (mm) was selected as a primary outcome measure for efficacy. The pain syndrome severity was estimated before administration of the drug (visit 1) and 4, 6, 8 and 12 h after the drug administration, as well as during visits 2 (day 2) and 3 (day 4). The McGill Pain Questionnaire, muscle syndrome index (MSI), Roland-Morris Disability Questionnaire pain estimates were used as the secondary diagnostic criteria. The percentage of patients with the positive response relative to baseline (the decrease in pain severity on VAS by more than 50%) was also determined. Results. The dynamics of the primary efficacy measure (pain severity on VAS) was as follows: 7.4 ± 0.92 cm (mean ± standard deviation) during visit 1, 5.6 ± 1.49 cm after 2 h, 4.6 ± 1.74 cm after 4 h, 3.0 ± 1.79 cm after 8 h; the VAS score was 2.3 ± 1.70 cm after 12 h (р&lt;0.001). The share of patients who responded to therapy (with the decrease in pain severity on VAS by more than 50% relative to baseline) was 84% [95% CI: 75.0 – 91.0] 24 h after the first administration, 94% during visit 3 [95% CI: 87.0 – 98.0], р&lt;0.001. The secondary efficacy criteria (muscle syndrome index and McGill Pain Questionnaire score) showed significant positive dynamics (р&lt;0.001). No systemic adverse events were reported. Conclusion. The study showed that a single intramuscular injection of Ambenium® parenteral was an efficient, well-tolerated and safe treatment option for low back pain. Administration of a single drug dose makes it possible to ensure a significant clinical effect reflected in the pain severity decrease and restoration of the patient’s motor activity.

Effects of CYP3A5*3 genetic polymorphisms on the pharmacokinetics of perampanel in Chinese pediatric patients with epilepsy.

This study was the first to evaluate the effect of CYP3A5*3 gene polymorphisms on plasma concentration of perampanel (PER) in Chinese pediatric patients with epilepsy. We enrolled 98 patients for this investigation. Plasma PER concentrations were measured using liquid chromatography-tandem mass spectrometry. Leftover samples from standard therapeutic drug monitoring were allocated for genotyping analysis. The primary measure of efficacy was the rate of seizure reduction with PER treatment at the final checkup. The plasma concentration showed a linear correlation with the daily dose taken ( r = 0.17; P < 0.05). The ineffective group showed a significantly lower plasma concentration of PER (490.5 ± 297.1 vs. 633.8 ± 305.5 μg/ml; P = 0.019). For the mean concentration-to-dose (C/D) ratio, the ineffective group showed a significantly lower C/D ratio of PER (3.2 ± 1.7 vs. 3.8 ± 2.0; P = 0.040). The CYP3A5*3 CC genotype exhibited the highest average plasma concentration of PER at 562.8 ± 293.9 ng/ml, in contrast to the CT and TT genotypes at 421.1 ± 165.6 ng/ml and 260.0 ± 36.1 ng/ml. The mean plasma PER concentration was significantly higher in the adverse events group (540.8 ± 285.6 vs. 433.0 ± 227.2 ng/ml; P = 0.042). The CYP3A5*3 gene's genetic polymorphisms influence plasma concentrations of PER in Chinese pediatric patients with epilepsy. Given that both efficacy and potential toxicity are closely tied to plasma PER levels, the CYP3A5*3 genetic genotype should be factored in when prescribing PER to patients with epilepsy.

Efficacy of Office-Based Salivary Ductal Steroid Irrigation for Managing Post-Irradiation Xerostomia in Head and Neck Cancer Patients: A Retrospective Study.

Post-irradiation xerostomia remains a significant quality of life concern for patients with head and neck cancers. Conventional therapies offer limited effectiveness. This study aims to investigate the therapeutic potential of office-based salivary ductal steroid irrigation in patients with post-irradiation xerostomia. This single-center observational study recruited 147 head and neck cancer patients suffering from post-irradiation xerostomia between November 2020 and October 2022. All included subjects received at least one round of successful salivary ductal cannulation and irrigation. The primary measure of efficacy was improvement in subjective xerostomia and objective salivary amylase levels. A logistic regression was employed to evaluate factors affecting treatment responsiveness. The response rate among nasopharyngeal cancer (NPC) patients was 74.8%, and that among non-NPC cancer was 65.6%, without significant intergroup differences. The statistical analysis revealed no significant influence of age, gender, or disease stage on treatment responsiveness. Post-treatment salivary amylase levels were significantly higher in responsive non-NPC patients. In conclusion, salivary ductal steroid irrigation emerged as a promising therapeutic modality for the management of post-irradiation xerostomia in head and neck cancer patients. While no explicit factors were predictive of responsiveness, the high rate of symptom improvement suggests that this therapy may be a viable alternative for patients that are refractory to standard treatments.

Abstract PO5-19-09: Trial in progress: A prospective randomized, controlled study to evaluate device efficacy for cutting and/or coagulation of tissue during mastectomy procedures

Abstract Background/Purpose: The ConMed HelixAR Electrosurgical Generator with Argon Beam Coagulation Technology (CHEST) trial aims to focus on patients undergoing mastectomy, either unilateral or bilateral, with immediate breast reconstruction including breast implants, tissue expander placement, or autologous flap. The study design follows the standard of care procedure with device efficacy being measured between two devices regularly used in the operative setting: the HelixAR Electrosurgical Generator (HEG) and the Conventional Electrosurgical Coagulation (CEC) systems. The need for safe alternative surgical tools is increasing as the number of women needing surgical treatment increases. Allowing for the test and comparison of these standardized devices gives an extent to the advantages of using one over the other. To evaluate the device effectiveness between the HelixAR Electrosurgical Generator and Conventional Electrosurgical Coagulation systems for cutting and/or coagulation of tissue during mastectomy and reconstruction surgery, we report the implementation in a randomized clinical trial. The study is powered to show superiority of the HEG to the CEC as it relates to the primary objective of time from post-mastectomy to hemostasis. The HEG is designed to deliver argon gas and high frequency electrical current compared to the CEC delivering high frequency electrical current only. The primary efficacy measure is the time it takes from post-mastectomy to hemostasis with the secondary effectiveness endpoints being infection, drain duration, total drain output, blood loss and device related adverse events. The study hypothesizes that the time for post-mastectomy hemostasis is significantly less for the HEG than the CEC. Additional hypotheses include overall less device related adverse events, lower blood loss, and reduced operative time in favor of the HEG. Methods: This is a prospective 1:1 randomized controlled study of the HEG versus the CEC for patients undergoing a mastectomy with reconstruction procedure. 82 patients will be enrolled and distributed in two arms of 41 patients with a primary objective to assess the device efficacy for cutting and coagulation. The subject population includes patients with breast cancer or high risk from genetic mutations and/or family history. Exclusion factors include known history of bleeding diathesis or coagulopathy, advanced refusal of blood transfusion, active systemic or cutaneous infection or inflammation. The enrolled patients will be followed for 2 months post-operatively. Results: The study is open with 53/82 (65%) patients enrolled at the time of the abstract submission. Of those, 26 subjects were randomized to the CEC and 27 to the HEG. 27 subjects have experienced an adverse or serious adverse event including bruising, infections, and wound dehiscence, none determined to be related to the device use. For the study, analysis will focus on the primary endpoint comparing post–mastectomy procedure time to hemostasis between the two devices. Conclusion: The CHEST trial demonstrates the feasibility of conducting a randomized controlled trial at a single center in a complex operative setting comparing two surgical modalities. The testing of these surgical devices provides rationale for the implementation of safe and regulated clinical trials. While both devices are FDA approved and regularly used, the standardization of device efficacy is becoming more prevalent as new innovations get introduced into the surgical setting. Citation Format: Jessica Montalvan, Ivan Marin, Logan Healy, Margarita Riojas-Barrett, Mary Bajomo, Elizabeth Bonefas, Alastair Thompson, Marco Maricevich, Sebastian Winocour, Stacey Carter. Trial in progress: A prospective randomized, controlled study to evaluate device efficacy for cutting and/or coagulation of tissue during mastectomy procedures [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-19-09.

Preservative-Free Bimatoprost 0.01% Ophthalmic Gel for Glaucoma Therapy: A Phase III Randomized Controlled Trial.

Noninferiority of efficacy was demonstrated for a preservative-free bimatoprost 0.01% compared with BAK-containing bimatoprost 0.01% following a 12-week treatment period in patients with open angle glaucoma or ocular hypertension. Improved tolerability, in particular conjunctival hyperemia, was also observed. To evaluate the intraocular pressure (IOP)-lowering efficacy and safety of a preservative-free bimatoprost 0.01% ophthalmic gel (PFB 0.01% gel) compared with preserved bimatoprost 0.01% (PB 0.01%). Phase III, international, multicenter, randomized, 2-parallel group, investigator-masked, 3-month treatment duration. Patients with glaucoma or ocular hypertension were randomized after a 7-week run-in/washout period to receive once-daily PFB 0.01% gel (n=236) or PB 0.01% (n=249) for 3 months. The primary efficacy measure was changed from baseline in IOP at week 12. Safety measures included adverse events (AEs) and assessment of conjunctival hyperemia. The mean changes from baseline in IOP at week 12 in the PFB 0.01% gel and PB 0.01% were -9.72±2.97 and -9.47±3.06 mm Hg, respectively, at 8 am , -9.41±3.03 and -9.19±3.12mm Hg at 10 am , and -8.99±3.36 and -8.54±3.44mm Hg at 4 pm . Noninferiority of PFB 0.01% gel to PB 0.01% was demonstrated at week 12 based on predetermined criteria (upper 95% CI margin of 1.5mmHg at all time points). The most frequently reported AE was conjunctival hyperemia; 13 (5.5%) patients with PFB 0.01% gel and 17 (6.8%) patients with PB 0.01%. The percentage of patients experiencing a worsening from baseline in conjunctival hyperemia score was lower with PFB 0.01% gel compared to PB 0.01% at week 6 (20.1% vs. 29.3%, respectively) and week 12 (18.3% vs. 30.4%, respectively). PFB 0.01% ophthalmic gel has the same efficacy in lowering IOP as PB 0.01% and demonstrated less aggravation of conjunctival hyperemia at weeks 6 and 12.

Impact of biologics on lung hyperinflation in patients with severe asthma

BackgroundIn asthma, inflammation affects both the proximal and distal airways and can cause significant hyperinflation, which is thought to be a major cause of dyspnea. MethodsThis is a retrospective observational study evaluating the effect of three months of treatment with different biologic drugs (benralizumab, dupilumab and omalizumab) on pulmonary hyperinflation in a cohort of patients with severe asthma already receiving regular triple inhaled therapy. Changes in RV, RV/TLC ratio, FRC and FRC/TLC ratio were the primary efficacy measures. Secondary outcomes included FEV1, FVC, FEV1/FVC ratio, IC, IC/TLC ratio, asthma control test, the percentage of eosinophils in the blood and fractional FENO. ResultsBenralizumab led to significant changes (p < 0.001) in RV, RV/TLC, FRC, and FRC/TLC. Dupilumab demonstrated a notable reduction in RV (p = 0.017) and RV/TLC (p = 0.002), but the decreases in FRC and FRC/TLC were merely numerical and not as pronounced as those induced by benralizumab. Omalizumab's positive impact on RV (p = 0.057) and RV/TLC (p = 0.085), as well as FRC (p = 0.202) and FRC/TLC (p = 0.096), was also predominantly numerical, with a tendency towards efficacy, albeit excluding the effect on FRC. Treatment with biologics resulted in improvements in all other lung function parameters assessed and a decrease in FENO levels. ConclusionThis study, although limited by small sample size, lack of a placebo control, and unbalanced group sizes, suggests that biological agents are effective in reducing lung hyperinflation even after a relatively short treatment.

Comparison of a preservative‐free bimatoprost 0.01% ophthalmic gel with a preserved bimatoprost 0.01% ophthalmic solution: A phase III, randomized, multicentre, 3‐month study

Purpose: The aim of this study was to evaluate the intraocular pressure (IOP)‐lowering efficacy and safety of a novel preservative‐free bimatoprost 0.01% ophthalmic gel (PFB 0.01% gel) compared with preserved bimatoprost 0.01% (PB 0.01%) in patients with ocular hypertension (OHT) or glaucoma.Methods: This was a randomized, multicentre (90 centres), investigator‐masked, 3‐month treatment duration, phase III trial. Following a 7‐week run‐in/washout period, patients were randomized to receive once‐daily PFB 0.01% gel (n = 236) or PB 0.01% (n = 249) for 3 months. The primary efficacy measure was change from baseline IOP at Week 12 at 3 timepoints. Noninferiority was based on a predetermined criteria (upper 95% confidence interval margin of 1.5 mmHg at all timepoints). Safety evaluations included conjunctival hyperaemia, ocular symptoms and occurrence of adverse events (AEs).Results: Mean change from baseline in IOP at Week 12 in the PFB 0.01% gel and PB 0.01% were − 9.72 ± 2.97 and − 9.47 ± 3.06 mmHg, respectively at 8 am, −9.41 ± 3.03 and − 9.19 ± 3.12 mmHg at 10 am, and − 8.99 ± 3.36 and − 8.54 ± 3.44 mmHg at 4 pm. Noninferiority of PFB 0.01% gel to PB 0.01% was demonstrated at Week 12 at all timepoints. The percentage of patients experiencing a worsening from baseline in conjunctival hyperaemia score was lower with PFB 0.01% gel compared to PB 0.01% at Week 12 (18.3% vs 30.4%, respectively). Ocular symptoms upon instillation were less frequent in the PFB 0.01% gel group compared to the PB 0.01% group at Week 12 for irritation/burning (12.7% vs 21.2%, respectively), itching (5.4% vs 10.4%) and eye dryness feeling (7.3% vs 14.3%). The most frequent treatment‐related AE was hyperaemia, reported in 15 (6.4%) patients in the PFB 0.01% gel group and 26 (10.4%) patients in the PB 0.01% group.Conclusions: PFB 0.01% ophthalmic gel had the same efficacy in lowering IOP as PB 0.01%, demonstrated less aggravation of conjunctival hyperaemia at Week 12 and less ocular symptoms upon instillation.

Beyond the headlines: On the efficacy and effectiveness of misinformation interventions

Research into how to best counter misinformation has enjoyed a great deal of popularity, but a discussion about how efficacy (successful lab studies) translates to effectiveness (real-world impact) is lacking. Lab studies have shown that many types of misinformation interventions are efficacious at achieving their intended outcomes (e.g., improving “discernment”, or the ability to distinguish true from false information). However, drawing on implementation science, we identify six challenges facing misinformation interventions research: (1) an overabundance of lab research and a lack of field studies; (2) testing effects which impede intervention longevity and scalability; (3) modest effects for small fractions of relevant audiences; (4) a reliance on item evaluation tasks (e.g., rating a series of headlines as true or false) as the primary efficacy measure of interest; (5) low replicability in the Global South and a lack of audience-tailored interventions; and (6) an underappreciation of potential unintended consequences of intervention implementation. We argue that it is time to look beyond item task performance as the primary outcome measure and to elevate both real-world outcomes and alternative measures of effectiveness (e.g., intervention attractiveness or user uptake) as equally important ways of assessing “what works”. We provide practical recommendations for addressing each challenge and improving intervention effectiveness.

Fractionated plasma separation and adsorption integrated with continuous veno-venous hemofiltration in patients with acute liver failure: A single center experience from China.

To evaluate the clinical efficacy and safety of fractionated plasma separation and adsorption integrated with continuous veno-venous hemofiltration (FPSA-CVVH) treatment in patients with acute liver failure (ALF). In this retrospective study, we enrolled patients with ALF (serum total bilirubin >10 mg/dL or Model for End-Stage Liver Disease [MELD] Score >18) hospitalized between August 2017 and August 2022. All patients had at least two sessions of FPSA-CVVH. The primary measure of treatment efficacy was the reduction ratios (RRs) of bilirubin after each session of FPSA-CVVH. Seventy-eight patients with ALF were enrolled. The MELD score at baseline was 22.9 ± 7.5. The mean total bilirubin was 22.05 ± 5.94 mg/dL, direct bilirubin was 16.33 ± 4.60 mg/dL and indirect bilirubin was 3.43 ± 1.60 mg/dL. One hundred and eighty seven sessions of FPSA-CVVH treatment lasting 8 hours each were performed. After a single session, serum total bilirubin, direct bilirubin and indirect bilirubin were significantly decreased. RRs were 52.0% ± 7.6% for total bilirubin, 59.4% ± 13.0% for direct bilirubin and 36.9% ± 15.4% for indirect bilirubin. Twenty nine patients (37.2%) survived and were discharged from the hospital, 12 of them recovered their liver function while the remaining 17 patients needed intermittent artificial liver support therapy. FPSA-CVVH therapy is an effective artificial liver support therapy in patients with ALF. It may be considered as a "bridge technique" to the recovery of liver function in critical ill patients with ALF.

The Comparison of Efficacy and Safety Between General and Topical Anesthesia on Micro-Plasma Radiofrequency Treatment for Hypertrophic Scar: A Retrospective Cohort Study.

While micro-plasma radiofrequency (MPR) treatment has a significant impact on hypertrophic scars, patients often require anesthesia to alleviate substantial discomfort. Currently, patients with similar degrees of scarring may choose surface anesthesia or general anesthesia based on their personal preferences. Nevertheless, the effectiveness and safety of different anesthesia modalities remain uncertain. To assess the effectiveness and safety of both general and surface anesthesia in MPR treatment for hypertrophic scars. We conducted a retrospective cohort study involving 101 patients diagnosed with hypertrophic scars who underwent MPR with different anesthesia methods. The primary measures of efficacy included the Vancouver Scar Scale (VSS) scores assessed before the first treatment and six months after the final treatment. Pain relief was evaluated using Visual Analog Scale (VAS) scores. Safety was assessed by comparing the incidence of adverse reactions between the two groups. Patients in the general anesthesia group showed a significant difference in scar pigmentation 6months after the treatment and lower pain level than those in the surface anesthesia group in the treatment of MPR. The difference in safety was not statistically significant. After adjusting for confounding factors and propensity score matching, the outcome of VSS and VAS scores was stable. General anesthesia, as opposed to surface anesthesia, appears to enhance both the effectiveness and safety of MPR while reducing postoperative pain in the treatment of hypertrophic scars. For patients with heightened pain sensitivity, general anesthesia may be the preferred treatment option. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors http://www.springer.com/00266 .