Similar Rates Of Adverse Events Research Articles

Web-based Telemonitoring of Visual Function and Self-reported Postoperative Outcomes in Cataract Care: an International Multicenter RCT.

Comparing web-based, self-administered follow-up after cataract surgery to conventional face-to-face follow-up. Eye clinics in the Netherlands, Austria and Germany. Randomized controlled trial with an embedded method comparison study [ClinicalTrials.gov: NCT04809402]. Routine cataract patients were randomized into two groups: the 'telemonitoring' group undertook web-based vision self-assessments and questionnaires from home, while the 'usual care' group received conventional care. All participants had a 4-6 week post-surgery clinic visit for safety and validation purposes. Outcomes included: the web-test's accuracy for assessing postoperative visual acuity (VA) and refractive error; adverse event rates; and patient reported outcome measurements (PROMs). 94 participants (188 eyes) were enrolled. Web-based uncorrected distance VA testing demonstrated a negligible mean difference (-0.03±0.14 logMAR) when compared to conventional ETDRS chart testing, with 95% limits-of-agreement ranging from -0.30 to 0.24 logMAR. The web-based refraction assessment overestimated the postoperative refractive error (mean difference 0.15±0.67 diopters), resulting in a poorer corrected distance VA compared to subjective refraction (mean 0.1 vs. -0.1 logMAR). Rates of adverse events and unscheduled consultations were minimal across both groups. Preoperative and postoperative PROMs questionnaires had a 100% response rate. Visual functioning (Catquest-9SF and NEI-VFQ-25) improved after surgery (mean improvement -0.80 and 16.70 respectively) and did not significantly differ between the two groups. The cataract patients in this study effectively provided postoperative outcome data via a web-interface. Both conventional and web-based follow-ups yielded similar PROMs and adverse event rates. Future developments should reduce the variability in the web-based VA test and yield representative refraction outcomes.

Update on the use of long-acting growth hormone in children.

After extensive research and many years of waiting, long-acting growth hormone (LAGH) formulations have finally become a reality in clinical practice and emerge as a potential solution to address the challenges of daily injections of recombinant human GH (rhGH). In this review, we present a brief history of the development of LAGH and provide a critical analysis of the existing literature on the five LAGH available and approved to date for treatment in children. In clinical trials, LAGH therapy has shown noninferiority compared with daily rhGH therapy in promoting linear growth in children with GH deficiency, with similar rates of adverse events. In the real world, many questions still need to be answered, such as whether a specific group of patients will benefit most from the weekly injection, whether compliance will be better compared with daily rhGH, whether long-term efficacy, monitoring and safety profile will be the same for the different LAGH compounds, and whether the cost-effectiveness will justify their use in different settings.

Intraductal radiofrequency ablation plus biliary stent versus stent alone for malignant biliary obstruction: a systematic review and meta-analysis.

Background and study aims Recurrent biliary stent occlusion and tumor ingrowth remain a major concern among patients with malignant biliary obstruction (MBO) with significant impact on patient morbidity and survival. Intraductal radiofrequency ablation (RFA) has emerged as a promising treatment that seeks to extend stent patency. This study aimed to evaluate the impact of RFA on overall survival (OS) and stent patency among patients with unresectable MBO. Methods A comprehensive search of electronic databases was performed for randomized controlled trials (RCTs) comparing RFA plus biliary stent (RFA+S) versus biliary stent alone (S-alone). Outcomes assessed included overall survival, stent patency, and adverse events (AEs) with mean difference (MD) calculated from pooled proportions. Subgroup analyses were performed for hilar strictures and cholangiocarcinoma (CCA). Results Six RCTs (n=439 patients) were included and demonstrated improved survival among patients who received RFA+S (MD 85.80 days; 95% confidence interval [CI] 35.02-136.58; I 2 =97%; P <0.0009). The pooled MD for total stent patency was 22.25 days (95% CI 17.38-61.87; I 2 =97%; P =0.27). There was no difference in AEs between RFA+S vs S-alone ( P >0.05). On subgroup analyses, RFA+S was associated with improved stent patency (MD 76.73 days; 95% CI 50.11-103.34; I 2 =67%; P <0.01) and OS (MD 83.14 (95% CI 29.52-136.77; I 2 =97%; P <0.01] for CCA. For hilar strictures, stent patency was improved among patients with RFA+S [MD 83.71 days (95% CI 24.85-142.56; I 2 =84%; P <0.01]. Conclusions RFA+S improved OS in the treatment of MBO when compared with S-alone. Moreover, the RFA therapy prolonged stent patency in hilar strictures and CCA, with similar rates of AEs.

Cryoballoon ablation of atrial fibrillation in octogenarians: one year outcomes from the cryo global registry

Abstract Background Limited information is available on the safety and efficacy of cryoballoon ablation (CBA) in elderly patients with atrial fibrillation (AF). Moreover, global utilization of CBA in this population (≥ 80 years old) has not been reported. This study’s objectives were to determine the use, efficacy, and safety of CBA to treat octogenarians suffering from AF. Methods In this sub-analysis of the Cryo Global Registry, 12-month outcomes of treating AF via CBA in octogenarians were compared to patients &lt; 80 years old. Efficacy was evaluated as time to a ≥ 30 s atrial arrhythmia (AA) recurrence. Healthcare utilization was determined via repeat ablations and hospitalizations. Improvement upon disease burden was evaluated through patient reporting of symptoms and the EQ-5D-3L quality of life (QoL) survey. Results The octogenarian cohort (n = 101) had a higher prevalence of females (51.5% vs 35.7%) and CHA2DS2-VASc scores (4.2 ± 1.3 vs 2.0 ± 1.5) compared to the control cohort (n = 1573, both p &lt; 0.01). Even when adjusting for baseline characteristics and antiarrhythmic drug usage, freedom from AA recurrence at 12 months (80.6% vs 78.9%, HRadj:0.97 [95% CI:0.59–1.58], p = 0.90) was comparable between octogenarians and control, respectively. Similar serious adverse event rates were observed between octogenarians (5.0%) and control (3.2%, p = 0.38). The groups did not differ in healthcare utilization nor reduction of AF-related symptoms from baseline to follow-up, but both experienced an improvement in QoL at 12 months. Conclusions Despite more age-related comorbidities, CBA is a safe and effective treatment for AF in octogenarians, with efficacy and adverse events rates akin to ablations performed in younger patients. Clinical trial registration https://clinicaltrials.gov/ct2/show/NCT02752737 Graphical Abstract

Prior Diagnosis of Opioid Related Disorder is Associated with Higher Medical Resource Utilization Following Primary Hip Arthroscopy: A National Database Study

To compare adverse events, medical resource utilization, prescribing patterns, and revision surgery rates of patients with opioid-related disorders (ORDs) undergoing primary hip arthroscopy against a propensity-matched group with no opioid-related disorders (NORDs). The TriNetX database was queried between January 2015 and December 2020 using International Classification of Diseases, 10th Revision and Current Procedural Terminology codes to identify patients undergoing primary hip arthroscopy between ages 18 and 70 years. The ORD cohort was propensity matched in a 1:1 ratio to NORD patients based on age, sex, alcohol-related disorders, heart disease, hypertension, metabolic disorders, anxiety disorders, major depressive disorder, diabetes mellitus, and antidepressant prescriptions. Postoperative rates of adverse events and medical resources were compared within 90 days of procedure, prescriptions were compared within 1 year, and revision surgery was compared within 2 years. A total of 809 ORD patients were propensity matched in a 1:1 ratio to NORD patients. Postoperative adverse events were similar between groups (P= .693). Rates of revision arthroscopy were also similar for both ORD (9.3%) and NORD (8.0%) cohorts (odds ratio [OR], 1.17; 95% confidence interval [CI], 0.83-1.66; P= .377). ORD patients received care from the emergency department, inpatient admission, outpatient visit, and physical therapy evaluations at higher rates. The ORD cohort received a greater amount of new opioid (OR, 2.66; 95% CI, 2.17-3.26; P < .0001) and antidepressant prescriptions (OR, 1.58; 95% CI, 1.26-1.97; P < .0001) compared to NORD patients within 1 year of surgery. ORD patients demonstrated similar rates of adverse events and revision surgery when compared to a propensity-matched group of NORD patients undergoing primary hip arthroscopy. However, ORD patients experienced increased rates of emergency department visits and hospitalizations and were prescribed higher rates of opioid and antidepressant prescriptions. Level III, cohort study.

Safety and Efficacy of Subcutaneous Daratumumab in Systemic AL Amyloidosis.

Systemic AL amyloidosis, a plasma cell dyscrasia, is characterized by the production of misfolded immunoglobulin light chain. These misfolded proteins aggregate into amyloid fibrils and deposit throughout the body, resulting in widespread organ dysfunction and ultimately death. Achieving rapid and maximal elimination of the plasma cell clone is crucial to long-term survival. Daratumumab, an anti-CD38 monoclonal antibody delivered intravenously, has been swiftly incorporated into standard first-line treatment regimens. A novel formulation of daratumumab has been developed that can be injected subcutaneously. As a retrospective qualitative review of prior publications involving daratumumab, this work briefly summarizes the existing data regarding the safety and efficacy of subcutaneous (SC) daratumumab, compared to intravenous (IV) daratumumab. SC daratumumab appears to deliver the same disease benefit as IV daratumumab to patients with decreased infusion-related reactions (IRRs), decreased time for administration, and similar rates of adverse events (AEs) intrinsically related to daratumumab. SC daratumumab is preferred over IV daratumumab, but the clinical situation ultimately should determine route of administration. Further investigation into cost-effectiveness benefit is warranted.

Ironing out the Wrinkles: Low Molecular Weight Iron Dextran and Premedications

Intravenous (IV) iron infusion increases hemoglobin levels and reduces the need for transfusions compared to oral iron in patients with iron deficiency. Low molecular weight iron dextran (LMW ID) has a boxed warning for anaphylactic-type infusion reactions and premedication is commonly given. However, a recent multi-institution cohort study showed similar rates of infusion-related adverse events (AEs) with iron sucrose (4.3%) and iron dextran (3.8%), and a 23-fold higher incidence of AEs among those who received premedication compared with those who did not (38.6% vs 1.7%). There is currently a national shortage of iron dextran. A study during a previous iron dextran shortage in 2016 showed that the increased use of newer IV iron formulations persisted even once the shortage ended. This may in part be due to the concern for infusion reactions, but the use of these formulations comes at a significant cost. An analysis of the US FDA database showed that, based on differences in the average price of iron sucrose and LMW ID, the cost to prevent one life-threatening AE related to the use of LMW ID was estimated to be 5.0-7.8 million dollars. The cost to prevent one LMW ID-related death was estimated to be 33 million dollars. To further evaluate the incidence of infusion reactions and the use of premedication at the University of Kansas Medical Center, we performed a retrospective analysis of all patients who received their first ever infusion of iron dextran between 1/1/2021-12/31/2022. Infusion reactions were characterized as severe if hypoxia (O2&amp;lt;90%), hypotension (&amp;lt;100/80) or hospital admission occurred. Ninety-six patients were identified. 17 (17.7%) were males and 79 (82.3%) were females. There were 49 (51%) Caucasian, 26 (27.1%) African Americans, 12 (12.5%) Hispanic, and 9 (9.4%) others. 8 patients had infusion reaction (8.3%; 95% CI 4.0-15.1%) as determined by review of nursing documentation. Serious infusion reactions with LMW ID were rare (n=2, 2.1%), and neither patient required epinephrine administration nor hospitalization. Patients with history of allergies (n=61, 63.5%) had a higher incidence of AEs compared to those who did not (13.1% [95% CI, 6.4-23.2%] vs 0.0%, P = 0.022). This was even higher in 27 (28.1%) patients with 3 or more allergies (18.5% [95% CI, 7.4-35.9%] vs 0.0%, P = 0.019). In 71 (80.2%) patients who received premedication, there was a lower incidence of AEs compared to those who did not (3.9% vs 26.3%; χ2 = 10.02; P =0.007). The incidence of AEs was compared with individual premedication, and lower incidences were seen in 64 (66.7%) patients with diphenhydramine (3.1% vs 18.8%, χ2 = 6.82; P =0.015), 50 (52.1%) with methylprednisolone (2.0% vs 15.2%, χ2 = 5.48; P =0.022), and 46 (47.9%) with acetaminophen (0.0% vs 16%, χ2 = 8.03; P =0.004). Notably, a variety of premedication combinations and doses were used, indicating a lack of standardization even within a single institution. No patient who received acetaminophen experienced an infusion reaction. By contrast, there was no significant difference in patients receiving famotidine, suggesting that while acetaminophen may be a useful premedication, famotidine may not be beneficial. Further, our data strongly suggests that patients without a history of drug allergies do not require premedication. Our retrospective study demonstrates significant benefit to receiving premedication, which is divergent when compared to previous studies. This may be due to several reasons: the previously mentioned multi-center study included multiple formulations of IV iron, had a much lower rate of premedication (6% vs. 80%), and used a different definition of infusion reaction. In the multi-center cohort study, administration of medications post-iron infusion was used as a surrogate marker of reaction, while in our study it was based on review of nursing documentation. Both our study and the prior multi-center study noted an increased incidence of infusion reactions in patients with a history of allergies, and both demonstrated the rarity of serious reactions. Based on these results and the prior studies indicating the increased cost of other IV iron formulations, consideration of reinstitution of LMW ID with de-escalation of premedication in those without history of drug allergies should be considered once the current drug shortage resolves.

Comparison of Drug-Coated Balloon and Drug-Eluting Stent for the Treatment of Small Vessel Disease (from the Dissolve SVD Randomized Trial)

The Dissolve drug-coated balloons (DCBs) is a new-generation DCB coated with paclitaxel of balloon surface, with midchain triglyceride excipient. Although the use of DCBs is a promising technique, little is known about the the clinical efficacy of the novel Dissolve DCB in coronary small vessel disease. This study was a prospective, randomized, multicenter, noninferiority trial comparing the Dissolve DCB with the Resolute drug-eluting stent (DES) in patients with a reference vessel diameter ≥2.25 and ≤2.75mm. Patients with a reference vessel diameter ≥2.00 and <2.25mm were enrolled in the very small vessel registry. The angiographic and clinical follow-up were planned at 9months and 1year in all patients, respectively. The primary end point was 9-month in-segment percentage diameter stenosis. A total of 247 patients with small vessel disease from 10 Chinese sites were included (Dissolve DCB, n=118; Resolute DES, n=129); 30 patients were treated with the DCB in the very small vessel cohort. The 9-month in-segment percentage diameter stenosis was 31.2 ± 2.0% with Dissolve DCB versus 26.1 ± 2.1% with Resolute DES; the 1-sided 97.5% upper confidence limit of the difference was 10.3% (p for noninferiority=0.0002). At 12months, the DCB and DES groups were associated with similar rates of target lesion failure (8.5% vs 6.1%, p=0.28) and major adverse cardiac and cerebrovascular events (20.9% vs 13.6%, p=0.12). In conclusion, the Dissolve DCB was noninferior to the Resolute DES for the primary end point of 9-month in-segment percentage diameter stenosis in this multicenter, head-to-head, randomized trial (a safety and efficacy study of Dissolve In Treatment Of Coronary Small Vessel Disease; NCT03376646).

Abstract 17786: Transcatheter Atrial Septal Defect With Deficient Retro-Aortic Rim Closure Success Rate and Complication is Similar to Other Anatomical Variants: Meta-Analysis

Introduction: Atrial septal defect (ASD) is a common congenital cardiac malformation resulting from incomplete fusion of one of the multiple embryological structures. Though surgical repair when indicated had been the norm, technological advances over the years have led to the current availability of transcatheter closure of the ASD. This alternative approach has been associated with lower complications and mortality but the procedural success and outcome are variable dependent upon anatomical features. Hypothesis: Several reports have linked deficiency of retro-aortic rim to higher complications, particularly aortic erosion in patients undergoing transcatheter ASD closure. Recent retrospective studies have however suggested otherwise. We herein performed meta-analysis of existing data on the success rate and adverse events following transcatheter closure of ASDs in patients with deficient retro-aortic rims (DRAR) in an attempt to provide general recommendations on the optimal approach for this common anatomic variant. Methods: Twelve relevant studies of ASD with DRAR were identified utilizing PubMed. Each of the twelve studies was closely reviewed for major adverse events including cardiovascular mortality, mortality from non-cardiovascular causes, device erosions, device embolization, residual shunting post-ASD repair, and other complications. The incident of each major adverse events was subsequently tabulated. Five of these reports directly compared the failure rates of ASD closure between patients with and without DRAR. A Mantel-Haenszel random effect meta-analysis was performed on these five publications. Results: Of the total 4,621 transcatheter-based approach ASD closures included, the rate of major adverse events was 5.14%. There was no significant difference in the procedural failure rate between those with and without DRAR ( relative risk =1.14, 95% CI[0.39 3.35], p=0.811 ), (heterogeneity, I 2 =74.75%). Conclusions: Our meta-analysis suggests that transcatheter ASD closure could be performed in patients with deficient retro-aortic rim ASD with expected similar rates of adverse events and success rates as in other anatomical variants.

Adjunctive Right Atrial Ablation for Persistent Atrial Fibrillation With Right Atrial Enlargement: A Pilot Study

BackgroundPersistent atrial fibrillation (PerAF) is often associated with right atrial (RA) enlargement. We investigated the efficacy of RA intervention in patients with PerAF and RA enlargement. MethodsPatients with PerAF and RA enlargement were randomised (1:1) to receive adjunctive RA ablation (left atrial [LA] + RA group; n = 60) or to receive LA ablation alone (LA-only group; n = 60). In the LA + RA group, RA ablation was performed if LA ablation failed to terminate AF. The primary end point was freedom from AF/atrial tachycardia (AT) recurrence at 12 months after a single ablation procedure without antiarrhythmic drug therapy. ResultsIn the LA + RA group, 40 patients (67%) required RA ablation. The LA + RA group had a higher rate of acute AF termination than the LA-only group (63.3% vs 36.7%; P = 0.003). At the end of 12-month follow-up, 42 patients (70%) in the LA + RA group were free of AF/AT recurrence, compared with 31 (51.7%) in the LA-only group (log rank P = 0.034; hazard ratio 0.549, 95% confidence interval 0.310-0.974). The rate of freedom from AF recurrence was also higher in the LA + RA group than in the LA-only group (81.7% vs 63.3%; log rank P = 0.019). The 2 groups had similar rates of adverse events (5% vs 3.3%; P = 0.648). ConclusionsAdjunctive RA ablation increased the success rate of a single ablation in patients with PerAF and RA enlargement. Chinese Clinical Trial RegistrationChiCTR220056844

Matching-Adjusted Indirect Comparison of the Long-Term Efficacy Maintenance and Adverse Event Rates of Lebrikizumab versus Dupilumab in Moderate-to-Severe Atopic Dermatitis.

Lebrikizumab and dupilumab are monoclonal antibodies approved for treating moderate-to-severe atopic dermatitis (AD). Both have demonstrated efficacy and safety over the 16-week SOLOs and ADvocate trials. However, AD is a chronic and relapsing inflammatory disease, and the long-term maintenance of efficacy is critical for achieving disease control from the perspective of patients, physicians, and regulatory agencies. This study aims to compare the long-term efficacy and safety of lebrikizumab every 4weeks (Q4W) and dupilumab every week or every 2weeks (QW/Q2W) among adult patients who have achieved treatment efficacy following the induction period of 16weeks. Lebrikizumab's efficacy was assessed using individual patient data (IPD) from the ADvocate 1 and 2 monotherapy trials. Dupilumab's efficacy was evaluated using aggregate data from the adult-exclusive SOLO-CONTINUE trial. Due to the absence of a common comparator trial arm, we employed an unanchored matching-adjusted indirect comparison (MAIC), a robust methodology widely accepted by health technology assessment (HTA) agencies. This re-weights ADvocate IPD to align with SOLO-CONTINUE's prognostic factors and effect modifiers. We compared lebrikizumab's adjusted outcomes with dupilumab outcomes at week52, focusing on 75% improvement in the Eczema Area and Severity Index from baseline (EASI-75), Investigator's Global Assessment (IGA) score of 0 or 1, and overall adverse event (AE) rates. Sensitivity analyses were conducted to test various combinations of matching variables. Adults on lebrikizumab Q4W were more likely to maintain IGA 0/1 through the 36-week maintenance period (weeks16-52) compared with those on dupilumab QW/Q2W [risk ratio (RR) 1.334; 95% confidence interval (CI) 1.02-1.74; p = 0.035]. Both treatments demonstrated comparable efficacy in terms of EASI-75 maintenance (RR 0.937; 95% CI 0.78-1.13; p = 0.490) and similar AE rates (RR 1.052; 95% CI 0.90-1.23; p = 0.526). Sensitivity analyses substantiated these findings. Our findings suggest that lebrikizumab Q4W may provide equal or superior long-term maintenance of efficacy measured with EASI-75 and IGA 0/1 compared with dupilumab QW/Q2W, with the advantage of requiring less frequent doses.

Safety and Efficacy of Nusinersen and Risdiplam for Spinal Muscular Atrophy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

We performed a systematic review and meta-analysis of the efficacy and safety of nusinersen and risdiplam in the treatment of spinal muscular disease (SMA). We screened the literature published in Pubmed, Web of Science, Embase, and Cochrane before July 2023 to conduct randomized controlled trials to test the treatment of SMA patients with nusinersen and risdiplam. The data were analyzed using Review Manager 5.4 software and Stata version 15.0 software. A total of six randomized controlled trials were included, involving 728 SMA patients, to synthesize evidence. It is reported that nusinersen treatment was beneficial for increasing the score of the Hammersmith Functional Motor Scale-Expanded (HFMSE) (WMD: 4.90; 95% CI: 3.17, 6.63; p < 0.00001), Revised Upper Limb Module (RULM) (WMD: 3.70; 95% CI: 3.30, 4.10; p < 0.00001), and Hammersmith Infant Neurological Evaluation Section 2 (HINE-2) (WMD: 5.21; 95% CI: 4.83, 5.60; p < 0.00001). In addition, the risdiplam treatment group also showed statistically significant improvements in the HFMSE score (WMD:0.87; 95% CI: 0.05, 1.68; p = 0.04), the 32-item Motor Function Measure (MFM32) (WMD:1.48; 95% CI: 0.58, 2.38; p = 0.001), and (WMD: 1.29; 95% CI: 0.57, 2.01; p = 0.0005). Nusinersen and risdiplam did not cause a statistically significant increase in the RULM score for adverse events (OR: 0.93; 95% CI: 0.51, 1.7; p = 0.82) and for severe adverse events (OR: 0.77; 95% CI: 0.47, 1.27; p = 0.31). Our analysis found that nusinersen and risdiplam treatment showed clinically meaningful improvement in motor function and a similar incidence rate of adverse events compared with the placebo. Further research should be carried out to provide a direct comparison between the two drugs in terms of safety and efficacy.

Comparative Safety Analysis of Oral Antipsychotics for In-Hospital Adverse Clinical Events in Older Adults After Major Surgery : A Nationwide Cohort Study.

Antipsychotics are commonly used to manage postoperative delirium. Recent studies reported that haloperidol use has declined, and atypical antipsychotic use has increased over time. To compare the risk for in-hospital adverse events associated with oral haloperidol, olanzapine, quetiapine, and risperidone in older patients after major surgery. Retrospective cohort study. U.S. hospitals in the Premier Healthcare Database. 17 115 patients aged 65 years and older without psychiatric disorders who were prescribed an oral antipsychotic drug after major surgery from 2009 to 2018. Haloperidol (≤4 mg on the day of initiation), olanzapine (≤10 mg), quetiapine (≤150 mg), and risperidone (≤4 mg). The risk ratios (RRs) for in-hospital death, cardiac arrhythmia events, pneumonia, and stroke or transient ischemic attack (TIA) were estimated after propensity score overlap weighting. The weighted population had a mean age of 79.6 years, was 60.5% female, and had in-hospital death of 3.1%. Among the 4 antipsychotics, quetiapine was the most prescribed (53.0% of total exposure). There was no statistically significant difference in the risk for in-hospital death among patients treated with haloperidol (3.7%, reference group), olanzapine (2.8%; RR, 0.74 [95% CI, 0.42 to 1.27]), quetiapine (2.6%; RR, 0.70 [CI, 0.47 to 1.04]), and risperidone (3.3%; RR, 0.90 [CI, 0.53 to 1.41]). The risk for nonfatal clinical events ranged from 2.0% to 2.6% for a cardiac arrhythmia event, 4.2% to 4.6% for pneumonia, and 0.6% to 1.2% for stroke or TIA, with no statistically significant differences by treatment group. Residual confounding by delirium severity; lack of untreated group; restriction to oral low-to-moderate dose treatment. These results suggest that atypical antipsychotics and haloperidol have similar rates of in-hospital adverse clinical events in older patients with postoperative delirium who receive an oral low-to-moderate dose antipsychotic drug. National Institute on Aging.

Endoscopic dilation with bougies versus balloons in caustic esophageal strictures: 17-year experience from a tertiary care center.

Endoscopic dilation is the preferred management strategy for caustic esophageal strictures (CES). However, the differences in outcome for different dilators are not clear. We compared the outcome of CES using bougie and balloon dilators. Between January 2000 and December 2016, the following data of all the patients with CES were collected: demographic parameters, substance ingestion, number of strictures, number of dilations required to achieve ≥ 14mm dilation, post-dilation recurrence, and total dilations. Patients were divided into two groups for the type of dilator, i.e., bougie or balloon. The two groups were compared for baseline parameter, technical success, short- and long-term clinical success, refractory strictures, recurrence rates, and major complications. Of the 189 patients (mean age 32.17 ± 12.12years) studied, 119 (62.9%) were males. 122 (64.5%) patients underwent bougie dilation and 67 (35.5%) received balloon dilation. Technical success (90.1% vs. 68.7%, p < 0.001), short-term clinical success (65.6% vs. 46.3%, p value 0.01), and long-term clinical success (86.9% vs. 64.2%, p < 0.01) were higher for bougie dilators compared to balloon dilators. Twenty-four (12.7%) patients developed adverse events which were similar for two groups. On multivariate analysis, use of bougie dilators (aOR 4.868, 95% CI 1.027-23.079), short-term clinical success (aOR 5.785, 95% CI 1.203-27.825), and refractory strictures (aOR 0.151, 95% CI 0.033-0.690) were independent predictors of long-term clinical success. Use of bougie dilators is associated with better clinical success in patients with CES compared to balloon dilators with similar rates of adverse events.

NAVIO RATKA shows similar rates of hemoglobin-drop, adverse events, readmission and early revision vs conventional TKA: a single centre retrospective cohort study.

Despite widespread adoption of NAVIO robotic-assisted total knee arthroplasty (NAVIO RATKA) in clinical practice, clinical outcome in terms of adverse events and complications remains unclear. The purpose of this study was to compare adverse events, length of stay, surgical time, hemoglobin drop, early readmission rate and revision rate between conventional TKA (CTKA) and NAVIO RATKA. This single-centre retrospective cohort analysis compared 230 NAVIO RATKA patients to 489 CTKA patients with a minimal follow-up of 12 months. Baseline demographic and comorbidity parameters were collected, as well as length of stay, revision rate and reason for revision, early readmission rate (< 6w) and reason for readmission, post-operative hemoglobin levels, adverse events, surgical time and operating room time. Data were compared using Mann-Whitney U test for continuous data without normal distribution and ordinal data, categorical variables were compared using the Chi-square or Fisher exact test. There were no clinically relevant baseline demographic or comorbidity differences between groups. CTKA had shorter length of stay than NAVIO RATKA (5.0 days vs 5.4 days, p = 0.010) but trended towards a higher reoperation rate (4.1% vs 1.7%, p = .144, n.s). No differences were found in hemoglobin drop, readmission rate or overall incidence of adverse events, but CTKA showed more hematoma formation (1.6% vs 0%, p = .044) and higher incidence of periprosthetic joint infection (PJI) (1% vs 0%, p = n.s.), whilst NAVIO RATKA showed more periprosthetic fractures and persistent wound drainage (0.4% vs 2.2%, p = .038 and 0.6% vs 4.3%, p = .001, respectively). Surgical time remained significantly longer in NAVIO RATKA during all 230 cases (87 min vs 67.6 min) and showed a continuous downward trend. This study further validates the usage of NAVIO RATKA as a safe method to perform TKA, with comparable short term outcomes to CTKA in terms of early revisions and adverse events. Surgeons should be mindful of the differing adverse event profile in NAVIO RATKA and adjust their patient selection accordingly to ensure optimal outcomes. In addition, surgeons using NAVIO RATKA should expect a linear learning curve and a surgical time exceeding that of CTKA. Level III (therapeutic retrospective cohort study).

Comparison of Cyclosporine A and Cyclosporine A Combined with Corticosteroid in the Treatment of Acquired Pure Red Cell Aplasia

To evaluate the efficacy, safety and relapse of cyclosporine A (CsA) and CsA combined with corticosteroid (CS) as the frontline therapy for patients with newly diagnosed acquired pure red cell aplasia (aPRCA). The clinical features, treatment responses, relapses and clinical outcomes of patients with newly diagnosed aPRCA in Peking Union Medical College Hospital (PUMCH) from January 2015 to May 2020 were analyzed retrospectively. All the enrolled patients had been treated with either CsA or CsA+CS for at least 6 months and had been followed up for at least 12 months, with complete clinical data and consent forms. 96 patients including 72 treated with CsA and 24 treated with CsA+CS were enrolled. With comparable baseline characteristics and follow-up periods, patients treated with CsA or with CsA+CS had similar overall response rates (ORRs) and complete response rates (CRRs) at the 3rd, 6th and 12th month and at the end of follow-up (P>0.05). Meanwhile, no significant difference was found between the two groups in the optimal ORR, optimal CRR, time to response or time to complete response. CsA+CS and CsA groups had similar adverse event (AE) rates, but CsA+CS group had higher CS-related infection rate (P <0.05). One patient in CsA+CS group died of multiple infections. As for the relapse, the two groups had compatible relapse rates at different time points, time to relapse, overall relapse rate and relapse-free survival (P>0.05). CsA exposure time, rather than different therapy regimens, was the only influence factor for either ORR or relapse rate (P <0.05). CsA monotherapy has similar efficacy, AE rate and relapse rate as compared with CsA+CS for patients with newly diagnosed aPRCA, and shows less CS-related AEs such as infection.

Safety and efficacy of the FAKHRAVAC compared with BBIBP-Corv2 against SARS-CoV-2 in adults: a non-inferiority multi-center trial

BackgroundWe compared Fakhravac and BBIBP-Corv2 vaccines in a phase III trial.MethodWe conducted a multicenter, parallel-group, active-control, non-inferiority clinical trial with pragmatic considerations assessing the safety and efficacy of Fakhravac and BBIBP-Corv2 vaccines. We started with two randomized double-blind arms and added two non-randomized open-label arms (based on participant preference) because of slow recruitment. The adult population received 0.5 ml (10 µg per dose) intramuscular injections of Fakhravac or BBIBP-Corv-2 vaccines 21 days apart. The primary outcome was the occurrence of PCR-positive symptomatic Covid-19 disease 14 days or more after the second injection. A 10% non-inferiority margin to the reported 72.8% efficacy of BBIBP-Corv2 was assumed. Cox proportional hazard modeling was used to estimate hazard ratios and their 95% confidence intervals.ResultWe enrolled 24,056 adults in four groups (randomized-Fakhravac: 824, randomized-BBIBP-Corv2: 832; Non-randomized-Fakhravac: 19,429, Non-randomized-BBIBP-Corv2: 2971). All observed local and systemic adverse reactions were generally self-limited and resolved completely. We observed similar Serious Adverse Event (SAE) rates in the BBIBP-Corv2 (2.57, 95% CI 1.33–4.49) and Fakhravac (2.25, 95% CI 1.72–2.89) groups; none of which were related to the vaccines received. We recorded 9815 Medically Attendant Adverse Events (MAAE), 736 of which were categorized as somehow related. The rate of related MAAE in the Fakhravac was similar to the BBIBP-Corv2 groups (0.31 and 0.26 per 1000 person-day) in the randomized and considerably higher (0.24 and 0.07 per 1000 person-day) in the non-randomized arms. We observed 129 (35% of the 365 required by target sample size) events of PCR + symptomatic Covid-19 during four months of active follow-up in the randomized arm, demonstrating that those receiving the Fakhravac vaccine were significantly less likely (HR = 0.69; 95% CI 0.49–0.98) to be diagnosed with PCR + symptomatic Covid-19 compared with those receiving BBIBP-Corv2 vaccine. After adjusting for type I error using the O’Brien Fleming method, the Fakhravac vaccine was non-inferior to the BBIBP-Corv2 (assuming a 10% non-inferiority margin to the reported 72.8% BBIBP-Corv2 vaccine efficacy; HR < 1.35) (One-way test: HR = 0.66; 99.8% CI 0.38–1.15). In the non-randomized arm, the results were inconclusive (HR = 1.23; 95% CI 0.96–1.61). We observed 5 cases of hospitalized Covid-19 in the randomized arm, none of which occurred in the Fakhravac vaccine group. Those receiving the Fakhravac vaccine were four times less likely to go to the hospital because of a Covid-19 diagnosis (HR = 0.24; 95% CI 0.10–0.60). The vaccine efficacy of the Fakhravac vaccine is estimated to be 81.5% (95% CI 81–82.4%).ConclusionFakhravac inactivated SARS-CoV-2 vaccine has comparable safety and efficacy to the BBIBP-Corv2 vaccine.Trial registration This study was registered with the Iranian Registry of Clinical Trials (www.irct.ir: IRCT20210206050259N3).

Meta-Analysis of Efficacy and Safety of Intravenous Iron in Patients With Iron Deficiency and Heart Failure With Reduced Ejection Fraction

Iron deficiency is an independent risk factor for heart failure (HF) exacerbation. We aim to study the safety and efficacy of intravenous (IV) iron therapy in patients with HF with reduced ejection fraction (HFrEF). A literature search was conducted on MEDLINE (Embase and PubMed) using a systematic search strategy by PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) until October 2022. CRAN-R software (The R Foundation for Statistical Computing, Vienna, Austria) was used for statistical analysis. The quality assessment was performed using the Cochrane Risk of Bias and Newcastle-Ottawa Scale. We included 12 studies with a total of 4,376 patients (IV iron n=1,985 [45.3%]; standard of care [SOC] n=2,391 [54.6%]). The mean age was 70.37±8.14years and 71.75±7.01years in the IV iron and SOC groups, respectively. There was no significant difference in all-cause mortality and cardiovascular mortality (risk ratio [RR] 0.88, 95% confidence interval [CI]0.74 to 1.04, p<0.15). However, HF readmissions were significantly lower in the IV iron group (RR 0.73, 95% CI0.56 to 0.96, p=0.026). Non-HF cardiac readmissions were not significantly different between the IV iron and SOC groups (RR 0.92, 95% CI0.82 to 1.02, p=0.12). In terms of safety, there was a similar rate of infection-related adverse events in both arms (RR 0.86, 95% CI0.74 to 1, p=0.05). IV iron therapy in patients with HFrEF is safe and shows a significant reduction in HF hospitalizations compared with SOC. There was no difference in the rate of infection-related adverse events. The changing landscape of HFrEF pharmacotherapy in the last decade may warrant a re-demonstration of the benefit of IV iron with current SOC. The cost-effectiveness of IV iron use also needs further study.

Pembrolizumab Alone or With Chemotherapy for 70+ Year-Old Lung Cancer Patients: A Retrospective Study

ObjectiveFirst-line pembrolizumab alone, as approved for PD-L1 ≥50%, or with chemotherapy was analyzed in older non–small-cell lung cancer (NSCLC) patients, for whom evidence is scarce. Materials and MethodsA total of 156 consecutive ≥70 year-old patients treated between January 2016 and May 2021 were retrospectively analyzed. Tumor progression was verified through radiologic review, while toxicity was captured from records. ResultsPembrolizumab plus chemotherapy (n = 95) caused higher rates of adverse events (91% vs. 51%, P < .001), treatment discontinuation (37% vs. 21%, P = .034), and hospitalization (56% vs. 23%, P < .001), but similar rates of immune-related adverse events (irAEs, mean 35%, P = .998) compared to pembrolizumab monotherapy (n = 61). Progression-free (PFS) and overall survival (OS) were similar between the 2 groups (7 vs. 8 months, and 16 vs. 14 months in median, P > .25). Occurrence of irAEs was associated with longer survival in a 12-week landmark analysis (median PFS 11 vs. 5 months, hazard ratio [HR] 0.51, P = .001; median OS 33 vs. 10 months, HR 0.46, P < .001), but occurrence of other AEs not (both P > .35). A worse ECOG performance status (PS) ≥2, presence of brain metastases at diagnosis, squamous histology and lack of tumor PD-L1 expression were independent predictors of shorter PFS and OS in multivariable analysis (HR 1.6-3.9 for PFS and OS, all P < .05). ConclusionChemoimmunotherapy increases the rate of adverse events and hospitalization without prolonging PFS or OS in newly diagnosed NSCLC patients aged 70 years or older compared to pembrolizumab monotherapy. ECOG PS 2, presence of brain metastases at diagnosis, squamous histology and PD-L1 negativity are associated with poor outcome.

(064) Pharmacokinetics and Safety Outcomes of Compounded Versus Branded Testosterone Pellets in Men with Testosterone Deficiency: A Single-Center, Open-Label, Randomized Trial

Abstract Introduction Testosterone deficiency (TD) is a prevalent condition, especially in men ≥ 45 years old, and testosterone therapy (TTh) can improve quality of life in these patients. Objective In this abstract, we aim to evaluate the safety profile of compounded subcutaneous testosterone pellets and to compare the pharmacokinetics between compounded and FDA approved testosterone pellets (Testopel®) for TTh. Methods This was a prospective, Phase 3, randomized, non-inferiority clinical trial. We enrolled 75 men diagnosed with TD and randomized them 1:1 ratio to Testopel® and a 100mg compounded pellet group. The patients were implanted with their respective treatment: Testopel® (10 pellets of 75mg) or compounded testosterone pellets (8 pellets of 100mg). Results After randomization, there were 35 participants enrolled in the Testopel® 75mg arm and 40 participants in E100 arm. Serum T levels were similar between the groups at 2, 4 and 6 months, with most men (82%) dropping below 300 ng/dL by the end of the trial. Adverse events such as elevations in prostate specific antigen, estrogen and hematocrit in each group were similar. Most dropouts were related to persistent TD symptoms and serum T &amp;lt; 300ng/dL, with similar rates between the two groups in the study. Conclusions Men treated with Testopel® and compounded pellets had comparable serum testosterone levels and similar adverse events rates. Compounded testosterone pellets can provide an effective choice of long term TTh among men with TD comparable to Testopel®. Disclosure Yes, this is sponsored by industry/sponsor: Empower Pharmaceuticals. Clarification Industry funding only - investigator initiated and executed study. Any of the authors act as a consultant, employee or shareholder of an industry for: Empower Pharmacy.