Safety Outcomes Research Articles

Remote ischemic post-conditioning for neonatal encephalopathy: a safety and feasibility trial.

Despite implementation of therapeutic hypothermia (TH) for infants with neonatal encephalopathy (NE), a significant proportion of infants suffer neurodevelopmental impairment (NDI). Remote ischemic conditioning (RIC) is a proposed neuroprotective maneuver that has been studied in adults with brain injury, but it has not been previously investigated in infants with NE. We performed a prospective, randomized, safety and dose escalation study in 32 neonates with NE. Four cohorts of consecutive patients were randomized to RIC therapy, including four cycles of limb ischemia and reperfusion on progressive days of TH, or sham. Clinical, biochemical, and safety outcomes were monitored in both groups. All patients received the designated RIC therapy without interruption or delay. RIC was not associated with increased pain, vascular, cutaneous, muscular, or neural safety events. There was no difference in the incidence of seizures, brain injury, or mortality between the two groups with the escalation of RIC dose and frequency. We found that RIC is a safe and feasible adjunctive therapy for neonates with NE undergoing TH. This pilot study establishes critical safety and feasibility data that are necessary for the design of future studies to investigate the potential efficacy of RIC to reduce NDI. Remote ischemic conditioning (RIC) is a possible neuroprotective intervention in infants with hypoxic-ischemic encephalopathy (HIE). RIC can be administered concurrently with therapeutic hypothermia without any notable adverse events. Future studies will need to address potential efficacy of RIC to improve neurodevelopmental outcomes, as well as consider the ideal temporal window and dose for RIC in this patient population.

Semaglutide effects on safety and cardiovascular outcomes in patients with overweight or obesity: a systematic review and meta-analysis.

Semaglutide is a GLP-1 receptor agonist that provides a reduction in glycated hemoglobin and weight. The objective was to evaluate whether the use of semaglutide, in individuals with overweight or obesity, reduces cardiovascular outcomes and adverse effects (AE). The data bases Pubmed, Lilacs, Scielo, Scopus, Web of Science and Cochrane Library were surveyed. Initially, 3333 articles were found, of which 19 articles were included. An additional search included 19 studies, totaling 38 articles. Relative risk (RR) values were significant for hospitalization due to heart failure (HF) 0.24 95% CI 0.12-0.57 (n = 2; 1045 participants; I² = 0.18), death due to cardiovascular causes 0.83 95% CI 0.71-0.98 (n = 3; 24 084 participants; I² = 0.21), death from any cause 0.79 95% CI 0.70-0.89 (n = 3; 24 084 participants; I² = 0.07), coronary revascularization 0.76 95% CI 0.69-0.85 (n = 2;20 951 participants; I² = 0.41), and non-fatal myocardial infarction 0.76 95%CI 0.66-0.88 (n = 3; 24 084 participants; I² = 0.21), with a difference between the subgroups (p = 0.05), favoring the subcutaneous administration route. The RR of stroke was 0.65 95% CI 0.44-0.97 for patients with diabetes (n = 2; 6480 participants; I² = 0.66). There was no difference between the frequency of constipation and routes of administration, as well as between doses of oral semaglutide. The RR of adverse effects was only not significant for discontinuation of treatment for oral semaglutide. The use of semaglutide reduced 76% in hospitalization due to HF, 17% deaths due to cardiovascular causes, 21% deaths due to any cause, 24% non-fatal myocardial infarction, 24% coronary revascularization and 35% stroke (in patients with diabetes). The use of semaglutide was associated with a higher relative risk and frequency of most adverse effects evaluated.

Contemporary Rationales for Cemented Implant Restorations in the Esthetic Zone.

This article explores the ongoing relevance of cement-retained implant restorations, focusing on their contemporary rationales for their successful use. Comprehensive considerations include esthetic, positional, and occlusal factors alongside recent technological advancements designed to mitigate previous known challenges. In certain clinical scenarios, cement-retained implant restorations offer distinct advantages such as eliminating access holes for improved esthetics, particularly for malpositioned implants. Modern advancements in materials and techniques have enhanced their predictability, safety, and overall outcomes while minimizing biological risks. When performed within appropriate protocols, cement-retained implant restorations can effectively address diverse clinical challenges. Recent technical advancements further bolster their utility, supporting esthetic, technical, biomechanical, and biological outcomes in implant rehabilitation of the partially edentulous esthetic zone. Understanding the justifications and guidelines for cement-retained implant restorations, along with recent technological advancements, enables clinicians to optimize treatment outcomes with greater flexibility while minimizing common limitations in practice.

Improved Door-to-Needle Time After Implementation of Tenecteplase as the Preferred Thrombolytic for Acute Ischemic Stroke at a Large Community Teaching Hospital Emergency Department

Background: Acute ischemic stroke is a leading cause of death and long-term disability. To improve patient outcomes, timely restoration of blood flow to the ischemic brain tissue is vital. One reperfusion strategy includes the administration of thrombolytics. Historically, alteplase has been the thrombolytic of choice for acute ischemic stroke; however, given recent safety and efficacy data, tenecteplase has gained popularity due to its optimal pharmacokinetic profile. Objectives: This study compares outcomes between adult patients with acute ischemic stroke who received tenecteplase as the preferred thrombolytic versus alteplase. Methods: This was a single center, retrospective cohort study that included adult patients who received intravenous thrombolytic therapy, either tenecteplase 0.25 mg/kg or alteplase 0.9 mg/kg, for acute ischemic stroke from May 2021 to December 2023. The primary outcome was door-to-needle time. Secondary safety outcomes included the incidence of symptomatic intracerebral hemorrhage (ICH), any ICH on 24-hour follow-up imaging, major extracranial bleeding, and angioedema. Secondary efficacy outcomes included discharge with a favorable neurological outcome, discharge disposition, ICU length of stay, and overall length of stay. Secondary stroke metric times evaluated include door-to-computed tomography (CT) time, CT-to-needle time, neurologist notification-to-needle time, and thrombolytic decision-to-needle time. Results: Fifty patients were included in the alteplase group and 50 patients were included in the tenecteplase group. The primary outcome, door-to-needle time, was significantly shorter in the tenecteplase group (36 vs 30 minutes, P = .006). There were no statistically significant differences found in the secondary safety and efficacy outcomes. Patients who received tenecteplase experienced significantly faster CT-to-needle times (17 vs 11 minutes, P = .006), neurologist notification-to-needle times (32 vs 25 minutes, P = .001), and thrombolytic decision-to-needle times (9 vs 5 minutes, P < .001). Conclusions: In this retrospective, observational study, there was a statistically significant decrease in door-to-needle time with tenecteplase compared to alteplase. No significant differences in secondary safety and efficacy outcomes were observed.

Optimizing Urological Concurrent Robotic Multisite Surgery: Juxtaposing a Single-Center Experience and a Literature Review.

Introduction: This article juxtaposes case series with a systematic review to evaluate the feasibility, safety, and clinical outcomes of concurrent robotic multisite urological surgeries, specifically robot-assisted radical prostatectomy (RARP) and robot-assisted partial nephrectomy (RAPN), for synchronous prostate and kidney cancers. Aim: The aims of this study were to evaluate the feasibility, safety, and clinical outcomes of urological concurrent robotic multisite surgeries through a comparison of institutional findings with the existing literature. Materials and Methods: A retrospective analysis was conducted on eight institutional cases of concurrent robotic multisite surgeries performed between 2021 and 2024. The primary outcomes measured were operative time, blood loss, and postoperative complications. A systematic review of the literature was performed, searching PubMed, Embase, and Cochrane Library databases, with the last search conducted on 1 July 2024. Studies were included if they reported on concurrent robotic surgeries corresponding to the procedures performed at the institution, including RARP with RAPN, RARP with robotic transabdominal preperitoneal inguinal hernia repair (RTAPPIHR), and other multisite robotic surgeries. Risk of bias was assessed using the modified Newcastle-Ottawa Scale. Descriptive statistics were used to analyze operative time and blood loss, with confidence intervals (CIs) calculated to assess precision. Categorical variables, including postoperative complications, were summarized using frequencies and percentages. Heterogeneity was assessed using the I2 statistic, with values above 50% indicating substantial heterogeneity. A random effects model was applied when necessary, and sensitivity analyses excluded studies with high risk of bias. Results: We describe a unique docking technique employed in our procedures, which allows for atraumatic transitions between surgeries using the same port sites. Our institutional cases demonstrated the feasibility and safety of concurrent robotic multisite surgery, with a mean operative time of 315 min (95% CI: 290-340) and mean blood loss of 300 mL (95% CI: 250-350). There were no significant intraoperative complications reported. These findings are consistent with the literature, where mean operative times range from 390 to 430 min and blood loss ranges from 200 to 330 mL. Notably, no positive surgical margins or declines in postoperative renal function were observed in our cases. The systematic review included nine retrospective studies involving 40 cases of concurrent RARP and RAPN, as well as eleven studies including 392 cases of RARP combined with RTAPPIHR. The findings from these studies support the feasibility and safety of concurrent surgeries, showing similar rates of operative time, blood loss, and postoperative complications. Conclusions: Concurrent robotic multisite surgeries, such as RARP combined with RAPN or RTAPPIHR, appear to be safe and feasible. Our data suggest these procedures are non-inferior to separate surgeries in terms of safety and complication rates. Potential benefits, including reduced operative times, shorter hospital stays, and more efficient resource use, may translate into cost savings, although no formal cost-effectiveness analysis was conducted. Limitations include the small sample size, retrospective design, and lack of long-term follow-up. Prospective trials are needed to validate these findings and further refine the techniques. Funding: this review did not receive any external funding. Registration: this review was not registered in any public protocol registry due to its comparative retrospective nature.

Efficacy and Safety of Intravenous Tenecteplase Versus Alteplase in Treating Acute Ischemic Stroke With Diabetes and Admission Hyperglycemia.

The aim of this study was to investigate the efficacy and safety of tenecteplase versus alteplase in patients with acute ischemic stroke, considering their diabetes history and admission hyperglycemia status. This was a post hoc analysis of the TRACE-2 (Tenecteplase Reperfusion Therapy in Acute Ischemic Cerebrovascular Events-2) randomized clinical trial that enrolled patients in China between June 2021 and May 2022. Eligible patients with acute ischemic stroke for standard intravenous thrombolysis, but ineligible for endovascular thrombectomy, were randomly assigned (1:1) to tenecteplase or alteplase within 4.5 hours of symptom onset. Admission hyperglycemia was defined as plasma glucose >7.8 mmol/L. The primary efficacy and safety outcome were excellent functional outcome at 90 days (modified Rankin Scale score of 0-1) and symptomatic intracranial hemorrhage within 36 hours, respectively. The Cochran-Mantel-Haenszel χ2 test was used for the outcomes. Of the 1382 patients included, 369 (26.7%) had a history of diabetes, and 482 (34.9%) experienced admission hyperglycemia. The primary efficacy outcome, comparing tenecteplase to alteplase, was achieved in 93 (56.7%) versus 97 (48.3%) among patients with a history of diabetes (P=0.11) and 335 (64.6%) versus 300 (62.2%) among those without diabetes (P=0.45), respectively. The primary efficacy outcome for tenecteplase versus alteplase was comparable among patients with and without admission hyperglycemia (57.5% versus 53.9%, P = 0.44; 65.4% versus 60.4%, P=0.12, respectively). No significant difference in the risk of symptomatic intracranial hemorrhage within 36 hours was observed between tenecteplase and alteplase, regardless of diabetes history or admission hyperglycemia. This study demonstrated that intravenous tenecteplase exhibits similar clinical outcomes compared with alteplase, irrespective of the patient's glucose metabolism status. URL: https://clinicaltrials.gov; Unique identifier: NCT04797013.

Real-world six-month outcomes in patients switched to faricimab following partial response to anti-VEGF therapy for neovascular age-related macular degeneration and diabetic macular oedema.

Landmark studies reported on faricimab efficacy and safety predominantly in treatment naïve patients, but outcomes following switch from other anti-VEGF therapies are lacking. We evaluated patients switched to faricimab who hadpreviously shown a partial response to other anti-VEGF injections for neovascular age-related macular degeneration (nAMD) and diabetic macular oedema (DMO). Retrospective study at the Oxford Eye Hospital. Patients switched to faricimab from January to April 2023 with six months follow-up were identified via electronic medical records. A total of 116 patients (151 eyes) were included. In 88 patients with nAMD (107 eyes), mean visual acuity remained stable: 62±17 ETDRS letters at baseline; 62±18 at six months (p > 0.05). Central subfield thickness (CST) reduced from 294 ± 73 μm to 270 ± 53 μm (p < 0.05) at six months. Subretinal or intraretinal fluid was present in 102 eyes (95%) at baseline and 75 eyes (70%) at follow-up (p < 0.05). Pigment epithelial detachment height decreased from 233 ± 134 μm to 188 ± 147 μm (p < 0.05). Mean treatment interval increased by 1.7 weeks (p < 0.05) and was extended in 61 eyes (57%) at six months. In 28 patients with DMO (44 eyes), visual acuity remained stable: 69 ± 15 letters at baseline; 70±15 at six months (p > 0.05). CST reduced from 355 ± 87 μm to 317 ± 82 μm (p < 0.05). Mean treatment interval increased by 1.4 weeks (p < 0.05) and was extended in 21 eyes (46%) by six months. Switching to faricimab in treatment resistant eyes led to improved anatomical response and extended treatment interval in a significant proportion of patients. Ongoing review of real-world data will inform longer-term outcomes of safety and effectiveness.

Mode 2 critical systems practice for complex safety decisions: Reflections from New Zealand's dairy industry

AbstractPoor decision‐making contributes to disasters in complex industrial systems. Improving group decision‐making practices for safety‐critical interventions is crucial yet hindered by a fragmented safety science literature. Our study applies Jackson's critical systems practice (CSP) to a complex safety problem at a New Zealand dairy manufacturing facility. Reflective practice, employed in the study and writing this article, underlines CSP's usefulness in navigating complex emergent safety challenges. Key insights include clarifying cognitive complexity amongst participants early in an intervention, focusing more sharply on crucial safety outcomes by using critical facilitation and enhancing CSP's ‘Check’ stage using reflective practice. We conclude by calling on scholars to prioritise the application of CSP in real‐world contexts to deepen our understanding of systemic praxis and generate actionable improvements.

Dual Antiplatelet Versus Alteplase for Early Neurologic Deterioration in Minor Stroke With Versus Without Large Vessel Occlusion: Prespecified Post Hoc Analysis of the ARAMIS Trial.

Dual antiplatelet therapy (DAPT) was noninferior to alteplase in minor nondisabling strokes in the ARAMIS trial (Antiplatelet Versus R-tPA for Acute Mild Ischemic Stroke); however, early neurological deterioration (END) associated with vessel stenosis may benefit from DAPT. We investigated whether the efficacy of DAPT was greater than alteplase in minor strokes with no large vessel occlusion (LVO). This study was a prespecified post hoc analysis of the ARAMIS trial and included patients with responsible vessel examination in the as-treated analysis set of the ARAMIS trial who were divided into LVO group and non-LVO group. In each group, patients were further classified into DAPT and intravenous alteplase treatments. Primary outcome was END at 24 hours defined as more than or equal to 4-point National Institutes of Health Stroke Scale score increase compared with baseline, and safety outcomes were symptomatic intracerebral hemorrhage and bleeding events during study. The primary analysis was estimated with a risk difference calculated by a generalized linear model including adjusted different baseline characteristics between treatments. Of 723 patients from the ARAMIS trial, 480 patients were included: 36 were categorized into LVO group and 444 into non-LVO group, of whom 20 patients had END. Compared with intravenous alteplase, a lower proportion of END was found after DAPT treatment in the non-LVO group (adjusted risk difference, -4.8% [95% CI, -6.9% to -2.6%]; P<0.001), but not in the LVO group (adjusted risk difference, 2.3% [95% CI, -17.6% to 22.3%]; P=0.82). The interaction was marginally significant between groups (P=0.06). In the non-LVO group, a lower proportion of bleeding events was found after DAPT treatment than intravenous alteplase (adjusted risk difference, -6.4% [95% CI, -8.9% to -3.9%]; P<0.001). Other safety outcomes were similar between the 2 treatments. Among minor nondisabling acute ischemic stroke without LVO, DAPT may be superior to intravenous alteplase regarding preventing END with a better safety profile. URL: https://www.clinicaltrials.gov; Unique identifier: NCT03661411.

Multicenter clinical trial evaluating the safety and efficacy of mechanical thrombectomy using the Versi Retriever

BackgroundThis study aimed to elucidate the safety and efficacy of mechanical thrombectomy using the Versi Retriever in patients with acute ischemic stroke (AIS).MethodsThis was a prospective, multicenter, single-arm study conducted...

Tenecteplase compared to alteplase in real-world outcome: A Swedish Stroke Register study

Background: Tenecteplase is increasingly used off-label as an alternative to alteplase for ischemic stroke thrombolysis. Our aim was to evaluate the safety of tenecteplase versus alteplase in comprehensive real-world data. Methods: We compared the outcomes for adult patients with acute ischemic stroke treated with alteplase or tenecteplase, registered in the Swedish Stroke Register between January 1, 2018 and December 31, 2020. The primary outcome was symptomatic intracerebral hemorrhage or death during hospital stay. Secondary outcomes were death within 90 days, modified Rankin Scale at 90 days, and mean door-to-needle time (DNT). Results: There were no significant differences in age or risk factors between 6,560 patients (45% women, mean age 74) treated with alteplase and 888 patients (43% women, mean age 74) treated with tenecteplase, although tenecteplase was more commonly used in non-university hospitals, hospitals with high use of thrombolysis, and in wake-up strokes. Tenecteplase was not non-inferior compared to alteplase in terms of symptomatic intracerebral hemorrhage or death during hospital stay (13.2% vs. 10.7%, absolute risk difference [95% confidence interval, CI] 2.5% [0.1 to 4.9%], adjusted odds ratio 1.44 [1.07–1.94]). There were no significant differences in functional outcome or death at 90 days, but tenecteplase was associated with decreased DNT (mean difference 9 min). Conclusion: Tenecteplase was not non-inferior in safety outcome, although associated with decreased DNT. As accumulating randomized controlled studies support the non-inferiority of tenecteplase regarding functional outcome, it is important to keep scrutinizing the safety outcomes.

Extended long-term efficacy and safety of velmanase alfa treatment up to 12 years in patients with alpha-mannosidosis.

Enzyme replacement therapy (ERT) using velmanase alfa previously showed promising efficacy and safety outcomes for up to 4 years of therapy in patients with alpha-mannosidosis. This pooled analysis from two multicenter, open-label phase IIIb extension trials rhLAMAN-07 (N = 13; NCT01908712) and rhLAMAN-09 (N = 8; NCT01908725) evaluated the long-term effects of velmanase alfa. Sixteen patients who previously completed phase I-III rhLAMAN-02/-03/-04/-05/-08 trials and five ERT-naïve patients were enrolled. Patients received 1 mg/kg velmanase alfa once weekly. Endpoints included changes from treatment baseline (before initial dose of velmanase alfa in any trial) in serum oligosaccharides, 6-minute walk test (6MWT), 3-minute stair climb test (3MSCT), pulmonary function (forced vital capacity [FVC], % predicted), serum immunoglobulin G (IgG) levels, and adverse events. The overall cohort comprised 21 patients, divided by age at treatment baseline into pediatric (n = 14) and adult subgroups (n = 7). Distance walked according to 6MWT increased or stabilized in pediatric patients, while in adults either stabilization or slight decline was observed. Similarly, pediatric patients performed better in the 3MSCT. Changes in FVC, % predicted, were comparable in both subgroups up to ~6 years of observation, diverging thereafter. Overall, sustained serum oligosaccharide clearance and serum IgG level increase was observed upon treatment initiation and persisted until last common observation. Velmanase alfa treatment was generally well tolerated, with the majority of reported adverse events being of mild-to-moderate intensity. With follow-up of up to 12 years, long-term efficacy and safety outcomes indicate continued benefits of velmanase alfa in patients with alpha-mannosidosis.

Comparison of Pudendal Nerve Block and Spinal Anesthesia in Proctological Surgeries: Efficacy, Safety, and Patient Outcomes.

Background and Objectives: The selection of an appropriate anesthesia method is a critical factor in the surgical treatment of proctological diseases, significantly impacting patient outcomes and comfort. Pudendal nerve block (PNB) and spinal anesthesia (SA) are commonly employed in these surgeries, yet the optimal choice between the two remains debated. This study aims to compare the efficacy and safety of PNB and SA in patients undergoing surgical treatment for various proctological conditions, with a focus on postoperative pain management, functional outcomes, and complication rates. Materials and Methods: A prospective observational study was conducted on 590 patients who underwent proctological surgery under either PNB (n = 435) or SA (n = 155). Pain levels were assessed using the Visual Analog Scale (VAS), while functional outcomes were measured using the World Health Organization Disability Assessment Schedule (WHODAS 2.0). Statistical analysis was performed to compare the outcomes between the two groups. Results: Patients in the PNB group reported significantly lower postoperative VAS scores compared to those in the SA group, particularly in hemorrhoidectomy and laser hemorrhoidoplasty procedures. The PNB group also demonstrated superior functional outcomes, with lower postoperative WHODAS 2.0 scores and a reduced incidence of urinary retention compared to the SA group. Furthermore, the duration of surgery and hospital stay were significantly shorter for patients in the PNB group. Conclusions: The findings suggest that PNB may offer advantages over SA in proctological surgeries, particularly in terms of pain management, functional recovery, and reduced complication rates. PNB should be considered a viable alternative to SA, particularly in cases where rapid recovery and minimizing complications are priorities. Exceptions to this include specific proctological surgeries, such as those for malignant tumors in the region, complex anal fistulas, proctological conditions arising from inflammatory bowel diseases, and patients on immunosuppressive therapy. Further research is needed to confirm these results and optimize anesthesia selection in this context.

Risk-benefit analysis of a multi-site radiographer comment model for emergency departments.

Critical/urgent X-ray findings are not always communicated in an appropriate time frame to ED physicians. The practice of radiographers alerting referrers to clinically significant image findings (verbally, via image flags or written comment) is noted internationally but risk assessment data is unavailable in the literature. A hybrid radiographer comment and alert model was piloted in New South Wales and a risk-benefit assessment conducted for timely and safe communication of abnormal X-ray appearances to ED physicians. Radiographer comments (n = 1102) were provided to five New South Wales EDs by 69 radiographers for a period of 3-12 months. Site auditors classified comments as true positive (TP), false positive (FP) or indeterminate (ID) with respect to the radiology report. FP comments were investigated with ED referrers and a low-medium-high-risk assessment was provided by two independent reviewers. A total of 42 FP (3.9%; 95% confidence interval [CI] 2.9-5.3) comments were analysed for any adverse outcomes. Risk assessments demonstrated 37 low, 5 low-moderate and no high-risk cases. A total of 282 direct or potential patient benefits were identified (26.4%; 95% CI 23.8-29.1). A total of 42 radiology report discrepancies were incidentally found: (3.9%; 95% CI 2.9-5.3). Audit results demonstrated areas where the radiographer comment could mitigate risk. The provision of radiographer alerts with a written comment for ED was found to be low risk to patients in the pilot study. Radiographers communicating directly with the emergency team when abnormal image appearances are detected can reduce diagnostic error and improve patient safety and health outcomes.

Ventral Hernia Repair With a Hybrid Absorbable-permanent Preperitoneal Mesh.

To analyze device safety and clinical outcomes of ventral hernia repair with the GORE SYNECOR Preperitoneal Biomaterial (PRE device), a permanent high-strength mesh with bioabsorbable web scaffold technology. This multicenter retrospective review analyzed device/procedure endpoints and patient-reported outcomes in patients treated for hernia repair ≥1 year from study enrollment. Included in this analysis were 148 patients with a mean age of 56 years; 66.2% met the Ventral Hernia Working Group grade 2 classification. Median hernia size was 30.0cm 2 and 58.8% of patients had an incisional hernia. Repairs were primarily a robotic (53.4%) or open approach (41.9%). All meshes were placed extraperitoneal. Procedure-related adverse events within 30 days occurred in 13 (8.8%) patients and included 7 (4.8%) patients with surgical site infection, 2 (1.4%) with surgical site occurrence (SSO), 4 (2.7%) requiring readmission, and 3 (2.0%) who had reoperation. The rate of SSO events requiring procedural intervention was 2.7% (4 patients) through 30 days and 3.4% (5 patients) at 12 months. The rate of procedure-related surgical site infection remained at 4.8% through 12 months (no further reports after 30d) and 3.4% for SSO (2 reports after 30d). There were no site-reported clinically diagnosed hernia recurrences throughout the study. Median patient follow-up including in-person visit, physical examination, reported adverse event, explant, death, and questionnaire response was 28 months (n = 148). Median patient follow-up with patient questionnaire was 36 months (n = 88). Use of the PRE device, which incorporates the proven advantages of both an absorbable synthetic mesh and the long-term durability of a permanent macroporous mesh, is safe and effective in complex ventral hernia repairs. When used in the retromuscular space, the combination of these 2 materials had lower wound complications and recurrence rates than either type of material alone.

Effect of thrombolysis type on the efficacy of aspiration versus stent retriever first line thrombectomy: results from the AcT trial

BackgroundIntravenous (IV) tenecteplase is increasingly being used in lieu of alteplase for acute ischemic stroke. We sought to study the influence of IV tenecteplase versus IV alteplase on the efficacy...

Reproductive Coercion: Prevalence and Risk Factors Related to Relationship Health Knowledge and Skills.

Reproductive coercion is any behavior that limits a person's reproductive decision-making and can lead to negative health and safety outcomes. Previous research has explored reproductive coercion prevalence rates in clinical samples, as well as demographic risk factors for experiencing reproductive coercion. The purpose of this study is to assess the prevalence rates of two specific forms of reproductive coercion, pregnancy coercion and condom manipulation, in an ethnically and racially diverse sample of young females. We also explore the association between relationship health knowledge and skills with reproductive coercion. We used a sample of 143 females with previous sexual activity. Participants were diverse in terms of race, ethnicity, sexual orientation, and family immigration status. Descriptive statistics and logistic regression analyses were used to determine prevalence rates of pregnancy coercion and condom manipulation and the likelihood of experiencing reproductive coercion based on participants' knowledge and skills related to relationship health. Results revealed that 16.1% of the sample had experienced reproductive coercion, with all participants in this group reporting lifetime experiences of pregnancy coercion. Lifetime experiences of condom manipulation were reported by 6.3% of the sample. The most common form of reproductive coercion experienced by participants was being told by a partner not to use any birth control. Furthermore, results indicate that higher relationship health knowledge may be a protective factor for pregnancy coercion and condom manipulation. Likewise, higher decision-making skills in relationships and higher confidence in relationships may also protect against condom manipulation. Results from this study suggest implications for sexual and relationship health programming that expands education around consent, choice, decision-making, and communication around the use of contraception.

Duration of Benefit and Risk of Dual Antiplatelet Therapy up to 72 Hours After Mild Ischemic Stroke and Transient Ischemic Attack.

Clopidogrel-aspirin initiated within 72 hours of symptom onset is effective in patients with mild ischemic stroke or transient ischemic attack (TIA) in the Intensive Statin and Antiplatelet Therapy for Acute High-risk Intracranial or Extracranial Atherosclerosis (INSPIRES) trial. Uncertainties remain about the duration of the treatment effect. This study aimed to assess duration of benefit and risk of clopidogrel-aspirin in these patients. The INSPIRES trial was a 2*2 factorial placebo-controlled randomized trial conducted in 222 hospitals in China. The 2 treatments did not interact and were evaluated separately. In this study, we performed secondary analyses based on antiplatelet treatment. All patients with mild stroke or TIA of presumed atherosclerotic cause within 72 hours of symptom onset enrolled in the trial were included. Patients were randomly assigned to receive clopidogrel-aspirin on days 1-21 followed by clopidogrel on days 22-90 or aspirin alone for 90 days. The primary efficacy outcome was major ischemic event which included the composite of ischemic stroke and nonhemorrhagic death. The primary safety outcome was moderate-to-severe bleeding. We estimated the risk difference between the 2 treatments for each stratified week. All 6,100 patients in the trial were included (3,050 in each group). The mean age was 65 years, and 3,915 patients (64.2%) were men. Compared with aspirin alone, the reduction of major ischemic events by clopidogrel-aspirin mainly occurred in the first week (absolute risk reduction [ARR] 1.42%, 95% CI 0.53%-2.32%) and remained in the second week (ARR 0.49%, 95% CI 0.09%-0.90%) and the third week (ARR 0.29%, 95% CI -0.05% to 0.62%). Numerical higher risk of moderate-to-severe bleedings in the clopidogrel-aspirin group was observed in the first 3 weeks (absolute risk increase 0.05% [95% CI -0.10% to 0.20%], 0.10% [95% CI -0.09% to 0.29%], and 0.18% [95% CI -0.03% to 0.40%] in the first, second, and third weeks, respectively). Among patients with mild ischemic stroke or high-risk TIA of presumed atherosclerotic cause, the net benefit of clopidogrel-aspirin initiated within 72 hours of symptom onset was pronounced in the first week and continued to a lesser degree in the following 2 weeks, outweighing the low, but ongoing hemorrhagic risk. ClinicalTrials.gov Identifier: NCT03635749. This study provides Class II evidence that among patients with mild ischemic stroke or high-risk TIA of presumed atherosclerotic cause, the net benefit of clopidogrel-aspirin initiated within 72 hours of symptom onset was pronounced in the first week and continued to a lesser degree in the following 2 weeks, outweighing the low but ongoing hemorrhagic risk.

Impact of Manufacturing Process and Compounding on Properties and Quality of Follow-On GLP-1 Polypeptide Drugs.

The prevalence of follow-on and compounded products of glucagon-like peptide-1 analogs is increasing. We assessed glucagon-like peptide-1 analogs semaglutide and liraglutide for purity, potential immunogenicity, and expected stability, by comparing a representative selection of commercially available follow-on drug substances (DSs) and drug products (DPs) with their corresponding originators. Tests included several chromatography methods coupled with ultraviolet and mass spectrometry detectors, inductively coupled plasma optical emission spectroscopy, inductively coupled plasma mass spectrometry, nuclear magnetic resonance, dissolution analyses, in silico peptide/major histocompatibility complex II-binding prediction, and fibrillation assays. Overall, 16 injectable semaglutide, 8 oral semaglutide, and 2 injectable liraglutide follow-on products were analyzed alongside originator products. Compared with originator, follow-on injectable semaglutide DSs and DPs had new impurities and impurity patterns, including high molecular weight proteins, trace metals, anions, counterions, and residual solvents. Analyses showed that several commercialized follow-on oral semaglutide DPs had a markedly lower quantity of semaglutide than the label claim, while dissolution tests indicated different semaglutide and sodium N-(8-[2-hydroxybenzoyl] amino)caprylate (SNAC) release profiles, which may reduce bioavailability. Neoepitopes were identified in DS and DP semaglutide follow-ons, indicating potential immunogenicity. Fibrillation assays showed increased fibrillation tendency and reduced physical stability in liraglutide follow-on DP samples compared with originator. This study highlights that differences in the manufacturing processes of follow-on semaglutide and liraglutide (vs those used for originators) can result in several changes to the DSs and DPs. The impact of these changes on efficacy and safety outcomes remains unknown and should be investigated by clinical studies.

An Open-Label Extension Study Assessing the Long-Term Safety and Efficacy of Viloxazine Extended-Release Capsules in Adults with Attention-Deficit/Hyperactivity Disorder.

Viloxazine ER (extended-release capsules; Qelbree®) is a nonstimulant medication that has been approved by the United States Food and Drug Administration (FDA) for treatment of attention-deficit/hyperactivity disorder (ADHD) in children (> 6 years old) and adults. This phase 3 open-label extension to a pivotal phase 3, double-blind trial evaluated the long-term safety and continued efficacy of viloxazine ER in adults with ADHD. This was a multicenter, flexible-dose, open-label extension to a phase III, double-blind, placebo-controlled trial (NCT04016779). Viloxazine ER was initiated at 200 mg/day and adjusted (between 200 and 600 mg/day) to achieve optimal efficacy and tolerability. Trial enrollment was halted temporarily (24 March 2020 to 23 July 2020) due to the coronavirus disease 2019 (COVID-19) pandemic. Participants completing double-blind treatment during that time were offered delayed enrollment upon trial requalification. Safety outcomes were the primary objectives. Secondary objectives were efficacy outcomes, including the ADHD Investigator Symptom Rating Scale (AISRS), and were assessed relative to double-blind baseline (or trial re-entry baseline for those whose enrollment was delayed by the COVID-19 pandemic). Overall, 159 participants (133 immediate and 26 delayed rollover) received viloxazine ER, with a mean exposure of 265 ± 254.9 days. Adverse events (AEs) included (> 10% incidence) insomnia (13.8%), nausea (13.8%), headache (10.7%), and fatigue (10.1%). AEs led to discontinuation for 17.6% of participants [most commonly insomnia (2.5%), nausea (2.5%), and fatigue (1.9%)]. AISRS total score [baseline mean ± standard deviation (SD): 37.9 ± 6.3] improved by the first follow-up visit (-11.4 ± 9.5; week 2) with continued improvement at subsequent visits (last on-study visit: -18.2 ± 11.54). Similar patterns of improvement were seen for other measures of efficacy, including quality of life and executive function. Following initial dose optimization, most participants (73%) used viloxazine ER doses ≥ 400 mg/day, with 36% using doses of 600 mg/day. Long-term viloxazine ER use was well tolerated, with no new long-term safety findings. Improvements in ADHD symptoms and associated measures were sustained throughout trial participation. In total, 73% percent of adult participants in this long-term study used viloxazine ER doses of 400 mg or more during maintenance treatment. Clinicaltrials.gov Identifier: NCT04143217.