Efficacy Outcomes Research Articles

Safety, tolerability, and efficacy outcomes of the Investigation of Levetiracetam in Alzheimer's disease (ILiAD)study: a pilot, double-blind placebo-controlled crossover trial.

To assess whether the antiseizure medication levetiracetam may improve cognition in individuals with Alzheimer's disease who have not previously experienced a seizure. We performed a randomized, double-blind, placebo-controlled crossover pilot study in individuals with mild-to-moderate Alzheimer's disease. Electroencephalography was performed at baseline and those with active epileptiform discharges were excluded. Eligible participants were randomized to placebo for 12 weeks or an active arm of oral levetiracetam (4 weeks up-titration to levetiracetam 500 mg twice daily, 4 weeks maintained on this dose followed by 4 weeks down-titration to nil). Participants then crossed over to the other arm. The primary outcome was change in cognitive function assessed by the Oxford Memory Task, a task sensitive to hippocampal memory binding. Secondary outcomes included tolerability, other neuropsychological scales, and general questionnaires. Recruitment numbers were severely limited owing to restrictions from the COVID-19 pandemic at the time of the study. Eight participants completed both arms of the study (mean age 68.4 years [SD = 9.2]; 5 females [62.5%]). No participants withdrew from the study and there was no significant difference between reported side effects in the active levetiracetam or placebo arm. Measures of mood and quality of life were also not significantly different between the two arms based on participant or carer reports. In limited data analysis, there was no statistically significant difference between participants in the active levetiracetam and placebo arm on the memory task. This pilot study demonstrates that levetiracetam was well tolerated in individuals with Alzheimer's disease who do not have a history of seizures and has no detrimental effect on mood or quality of life. Larger studies are needed to assess whether levetiracetam may have a positive effect on cognitive function in subsets of individuals with Alzheimer's disease. Abnormal electrical activity within the brain, such as is seen in seizures, might contribute to memory problems in people with dementia. We completed a clinical trial to see if an antiseizure medication, levetiracetam, could help with memory difficulties in people with Alzheimer's disease (the most common cause of dementia). In this pilot study, we could not prove whether levetiracetam helped memory function. We did show that the drug is safe and well tolerated in people with dementia who have not had a seizure. This work, therefore, offers a platform for future research exploring antiseizure medications in people with dementia.

Efficacy and safety of 4-hydroxy-2-methyl-N-(5-methyl-2-thiazolyl)-2H-1, 2-benzothiazin-3-carboxamide 1,1-dioxide, a rapid-acting meloxicam formulation, for analgesia after orthopaedic surgery under general anaesthesia: a randomized controlled trial.

Postoperative pain management is one of the most challenging treatments after orthopaedic surgery, and improved medical treatment options are urgently needed. This study aimed to evaluate the efficacy and safety of 4-hydroxy-2-methyl-N-(5-methyl-2-thiazolyl)-2H-1, 2-benzothiazin-3-carboxamide 1,1-dioxide (QP001) for moderate to severe pain following orthopaedic surgery. This randomized clinical trial enlisted patients experiencing moderate to severe pain following orthopaedic surgery in 20 hospitals in China. We allocated randomly 132 participants to receive 30mg QP001 and 66 participants to receive 0.9% saline pre-surgery. The primary efficacy outcome was the total morphine consumption within 24h. The total morphine consumption in the QP001 group, versus placebo group, was significantly lower over the following 24h [12.53 (10.51) vs. 26.13 (13.98), P < 0.001]. The total morphine consumption in the QP001 group, versus placebo group, was also significantly decreased over the following 48h (P < 0.001). The QP001 group, versus placebo, showed a significant decrease in the effective pressing times of the analgesic pump, morphine relief analgesia ratio over the 24h and 48h periods and the area under the curve for pain intensity-time as well as a significant prolonged in the time of first pressing the analgesic pump and the time of first morphine rescue analgesia (P < 0.001). The QP001 groups, versus placebo, show no significant difference in adverse events, but the incidence of adverse drug reactions decreased (59.4% vs. 75.8%, P = 0.023). QP001 provides analgesia and reduces opioid consumption in patients with moderate to severe pain after orthopaedic surgery, with a favorable safety profile.

Timing of Orchidopexy; Efficacy and Safety Outcomes in Patients with Cryptorchidism: Systematic Review and Meta-Analysis

Timing of Orchidopexy; Efficacy and Safety Outcomes in Patients with Cryptorchidism: Systematic Review and Meta-Analysis

Comparative Efficacy and Safety of Novel Antiplatelets and Standard Therapy in Patients With Coronary Artery Disease.

Coronary artery disease (CAD) is a significant health concern that has affected approximately 110 million people worldwide. CAD is defined as persistent narrowing of the coronary arteries as a result of atherosclerotic plaque build-up. Acute coronary syndrome (ACS), which encompasses ST-elevation myocardial infarction (STEMI), non-ST-elevation myocardial infarction (NSTEMI), and unstable angina, often results from plaque ruptures. Platelets are crucial for atherogenesis, vascular inflammation, and oxidative stress. Antiplatelet therapy aimed at reducing thrombotic events is vital for ACS treatment. Clinical guidelines advise the use of dual antiplatelet therapy (DAPT) that combines aspirin and a P2Y12 receptor inhibitor (clopidogrel, prasugrel, or ticagrelor) in ACS patients undergoing percutaneous intervention (PCI). This study aimed to assess comprehensively the effectiveness and safety of ticagrelor and prasugrel in comparison to clopidogrel in patients with ACS. An extensive literature search was conducted using PubMed, PubMed Central (PMC), ScienceDirect, and EBSCO databases. The search revealed studies that compared ticagrelor and prasugrel to clopidogrel in ACS patients, and we selected these studies based on specific inclusion and exclusion criteria, which included observational studies, clinical trials, literature reviews, and meta-analyses involving adult ACS patients treated with ticagrelor, prasugrel, or clopidogrel. The efficacy outcomes were defined as major adverse cardiovascular events (MACE) and thrombotic events, whereas the safety outcomes were measured by major and minor bleeding and hemorrhagic stroke. After a rigorous quality assessment to minimize bias, 23 studies were selected for analysis. The findings indicated that novel antiplatelets reduced MACE but increased bleeding complications, with ticagrelor consistently associated with dyspnea.In conclusion, novel P2Y12 inhibitors provide cardiovascular benefits but require careful patient selection and monitoring due to gastrointestinal bleeding (GIB) risks. Future research should standardize bleeding definitions and assess long-term outcomes. Ticagrelor and prasugrel may be more effective and safer than clopidogrel in ACS patients. Given the high risk of GIB, especially among older individuals or those with a past stroke, it is advisable to suggest a lower prasugrel dose without raising the bleeding rates. Since fewer patients use the novel antiplatelet regimen compared to clopidogrel, future clinical trials should include a broader patient population and compare these regimens.

Pallidal neuronal activity in Gilles de la Tourette syndrome and dystonic patients: A comparative study.

Gilles de la Tourette syndrome (GTS) and dystonia (DYS) are both hyperkinetic movement disorders effectively treated by deep brain stimulation (DBS) of the internal part of the globus pallidus (GPi). In this study, we compared single-neuron activity in the GPi between 18 GTS patients (with an average of 41 cells per patient) and 17 DYS patients (with an average of 54 cells per patient), all of whom underwent bilateral pallidal stimulation surgery, under general anesthesia or while awake at rest. We found no significant differences in GPi neuronal activity characteristics between patients operated on under general anesthesia versus those who were awake, irrespective of their diagnosis (GTS or DYS). We found higher firing rates, firing rate in bursts, pause duration and interspike interval coefficient of variation in GTS patients compared to DYS patients. On the opposite, we found higher number of pauses and bursts frequency in DYS patients. Lastly, we found a higher proportion of GPi oscillatory activities in DYS compared to GTS patients, with predominant activity within the low-frequency band (theta/alpha) in both patient groups. These findings underscore the complex relationship between the different neuronal discharge characteristic such as oscillatory or bursting activity within the GPi in shaping the clinical phenotypes of hyperkinetic disorders. Further research is warranted to deepen our understanding of how neuronal patterns are transmitted within deep brain structures and to develop strategies aimed at normalizing these pathological activities, by refining DBS techniques to enhance treatment efficacy and individual outcomes.

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.

Endovascular thrombectomy for childhood stroke (Save ChildS Pro): an international, multicentre, prospective registry study.

Emerging evidence suggests that endovascular thrombectomy is beneficial for treatment of childhood stroke, but the safety and effectiveness of endovascular thrombectomy has not been compared with best medical treatment. We aimed to prospectively analyse functional outcomes of endovascular thrombectomy versus best medical treatment in children with intracranial arterial occlusion stroke. In this prospective registry study, 45 centres in 12 countries across Asia and Australia, Europe, North America, and South America reported functional outcomes for children aged between 28 days and 18 years presenting with arterial ischaemic stroke caused by a large-vessel or medium-vessel occlusion who received either endovascular thrombectomy plus best medical practice or best medical treatment alone. Intravenous thrombolysis was considered part of best medical treatment and therefore permitted in both groups. The primary outcome was the difference in median modified Rankin Scale (mRS) score between baseline (pre-stroke) and 90 days (±10 days) post-stroke, assessed by the Wilcoxon rank test (α=0·05). Efficacy outcomes in the endovascular thrombectomy and best medical treatment groups were compared in sensitivity analyses using propensity score matching. The Save ChildS Pro study is registered at the German Clinical Trials Registry, DRKS00018960. Between Jan 1, 2020, and Aug 31, 2023, of the 241 patients in the Save ChildS Pro registry, 208 were included in the analysis (115 [55%] boys and 93 [45%] girls). 117 patients underwent endovascular thrombectomy (median age 11 years [IQR 6-14]), and 91 patients received best medical treatment (6 years [3-12]; p<0·0001). The median Pediatric National Institutes of Health Stroke Scale (PedNIHSS) score on admission was 14 (IQR 10-19) in the endovascular thrombectomy group and 9 (5-13) in the best medical treatment group (p<0·0001). Both treatment groups had a median pre-stroke mRS score of 0 (IQR 0-0) at baseline. The change in median mRS score between baseline and 90 days was 1 (IQR 0-2) in the endovascular thrombectomy group and 2 (1-3) in the best medical treatment group (p=0·020). One (1%) patient developed a symptomatic intracranial haemorrhage (this patient was in the endovascular thrombectomy group). Six (5%) patients in the endovascular thrombectomy group and four (5%) patients in the best medical treatment group had died by day 90 (p=0·89). After propensity score matching for age, sex, and PedNIHSS score at hospital admission (n=79 from each group), the change in median mRS score between baseline and 90 days was 1 (IQR 0-2) in the endovascular thrombectomy group and 2 (1-3) in the best medical treatment group (p=0·029). Regarding the primary outcome for patients with suspected focal cerebral arteriopathy, endovascular thrombectomy (n=18) and best medical treatment (n=33) showed no difference in 90-day median mRS scores (2 [IQR 1-3] vs 2 [1-4]; p=0·074). Clinical centres tended to select children with more severe strokes (higher PedNIHSS score) for endovascular thrombectomy. Nevertheless, endovascular thrombectomy was associated with improved functional outcomes in paediatric patients with large-vessel or medium-vessel occlusions compared with best medical treatment. Future studies need to investigate whether the positive effect of endovascular thrombectomy is confined to older and more severely affected children. None.

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.

Pulmonary outcomes of incretin-based therapies in COPD patients receiving single-inhaler triple therapy

IntroductionPatients with chronic obstructive pulmonary disease (COPD) on triple therapy often face exacerbations and comorbidities. Emerging evidence suggests that glucagon-like peptide-1 (GLP-1) analogs may reduce the risk of exacerbation in patients with COPD and type 2 diabetes mellitus (T2DM). This study investigates the impact of GLP-1 analogs on pulmonary outcomes in patients with COPD on single-inhaler triple therapy (SITT) and T2DM.MethodsWe conducted a retrospective cohort study using the TriNetX database and analysed adult patients with COPD and T2DM who received SITT between April 2005 and July 2023. Patients were categorized into GLP-1 analog and dipeptidyl peptidase-4 inhibitors (DPP4i) cohorts. The primary efficacy outcome was COPD exacerbation and the secondary efficacy outcomes were pneumonia, acute respiratory distress syndrome, intubation, oxygen dependence, and all-cause mortality. The secondary outcomes were serious gastrointestinal adverse events.ResultsWe included 6898 patients, with 4184 receiving GLP-1 analogs and 2714 receiving DPP4i. After matching, 1751 GLP-1 analog users were matched with 1751 DPP4i users. GLP-1 analog users had an 18% lower risk of COPD exacerbation (hazard ratio [HR], 0.82 [95% CI: 0.71–0.94]), a 28% reduced risk of pneumonia (HR, 0.72 [95% CI: 0.61–0.85]), a 34% reduced risk of oxygen dependence (HR, 0.66 [95% CI: 0.47–0.91]), and a 40% decreased risk of all-cause mortality (HR, 0.60 [95% CI: 0.47–0.77]). No significant serious gastrointestinal adverse events were observed.ConclusionGLP-1 analogs may be associated with reduced COPD exacerbations, pulmonary comorbidities, and mortality in patients with COPD receiving SITT and T2DM, with no significant serious gastrointestinal safety concerns.

Efficacy and Cognitive Outcomes of Gamma Knife Radiosurgery in Glioblastoma Management for Elderly Patients.

Gamma Knife Radiosurgery (GKRS), a specific type of Stereotactic Radiosurgery (SRS), has developed as a significant modality in the treatment of glioblastoma, particularly in conjunction with standard chemotherapy. The goal of this study is to evaluate the efficacy of combining GKRS with surgical resection and chemotherapy in enhancing therapeutic effects for glioblastoma patients aged 55 years and older. This prospective clinical study, conducted in accordance with the STROBE guidelines, involved 49 glioblastoma patients aged 55 years and older, treated between January 2013 and January 2023. Data were collected prospectively, and strict adherence to the STUPP protocol was maintained. Only patients who conformed to the STUPP protocol were included in the analysis. Due to concerns regarding the cognitive impairment associated with conventional radiotherapy, and at the patients' request, a radiosurgery plan was offered. Radiosurgery was administered for 4-8 weeks following surgical resection. Any patients who had not received previous radiotherapy received open surgical tumor removal, followed by GKRS along with adjuvant chemotherapy. In this prospective clinical study of 49 glioblastoma patients aged 55 years and older, the average lifespan post-histopathological diagnosis was established at 22.3 months (95% CI: 12.0-28.0 months). The median time before disease progression was 14.3 months (95% CI: 13.0-29.7 months). The median duration until the first recurrence after treatment was 15.2 months, with documented cases varying between 4 and 33 months. The Gamma Knife Radiosurgery (GKRS) treatment involved a median marginal recommended dose of 12.5 Gy, targeting an average volume of 5.7 cm3 (range: 1.6-39 cm3). Local recurrence occurred in 21 patients, while distant recurrence was identified in 8 patients. Within the cohort, 34 patients were subjected to further therapeutic approaches, including reoperation, a second GKRS session, the administration of bevacizumab and irinotecan, and PCV chemotherapy. A cognitive function assessment revealed that the patients treated with GKRS experienced significantly less cognitive decline compared to the historical controls, who were treated with conventional radiotherapy. The median MMSE scores declined by 1.9 points over 12 months, and the median MoCA scores declined by 2.9 points. This study demonstrates that Gamma Knife Radiosurgery (GKRS), when integrated with surgical resection and adjuvant chemotherapy, offers a substantial benefit for glioblastoma patients aged 55 years and older. The data reveal that GKRS not only prolongs overall survival and progression-free survival but also significantly reduces cognitive decline compared to conventional radiotherapy. These findings underscore the efficacy and safety of GKRS, advocating for its incorporation into standard treatment protocols for older glioblastoma patients. The potential of GKRS to improve patient outcomes while preserving cognitive function is compelling and warrants further research to optimize and confirm its role in glioblastoma management.

Liquid nitrogen cryotherapy effectively and safely improves response of thick Actinic Keratoses lesions by 5-aminolevulinic acid-based photodynamic therapy: a randomized, prospective, single-blind trial

BackgroundActinic keratoses (AK) may progress into squamous cell carcinoma. Many combination therapies were used to improve the clearance rate. However, there are limited studies on the efficacy and safety of lesion-directed Liquid nitrogen cryotherapy combined with field-directed photodynamic therapy (PDT). ObjectiveThis study is aimed to determine the efficacy and safety of Liquid nitrogen cryotherapy combined with PDT in Chinese patients with actinic keratosis. MethodsA total of 61 patients with AK were selected at the Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College between August 2018 and August 2023. They were randomly divided into PDT plus Liquid nitrogen cryotherapy group(LN-PDT)and control PDT group(C-PDT)with 30 patients and 31 patients, respectively. 27 patients in the LN-PDT group and 28 patients in the C-PDT group completed the clinical sessions. Efficacy, adverse effects, and cosmetic outcomes were recorded and compared between the two groups. Results3 months after the final treatment, the clearance rates for total AK lesions were 97.4%(449/461) in the LN-PDT group and 93.4%(456/488)in the C-PDT group (P < 0.05). For grade I AK lesions, the clearance rates were 99.2% (234/237) for the LN-PDT group and 98.3% (237/241) for the C-PDT group (P >0.05). For grade II lesions, the clearance rates were 97.5% (156/160) for the LN-PDT group and 91.9% (172/186) for the CPDT group (P < 0.05). For grade III lesions, the clearance rates of the LN-PDT and C-PDT groups were 87.5% (58/64) and 78.7% (47/61), respectively (P < 0.05). The two groups had no significant differences in pain, erythema, edema, hyperpigmentation and scarring. Cosmetic outcomes mainly were excellent or good in both groups with no significant difference. ConclusionLiquid nitrogen cryotherapy combined with PDT showed higher efficacy on grade II and grade III AK lesions than PDT alone. The two groups have similar adverse effects and cosmetic outcomes.

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...

A Randomized Controlled Trial of a Digital Intervention to Improve the Sexual Health of Adolescent and Young Adult Male Emergency Department Patients

PurposeTo assess implementation outcomes and potential efficacy of a user-informed, theory-based digital health intervention developed to improve adolescent and young adult (AYA) male sexual health. MethodsWe conducted a pilot randomized controlled trial of sexually active male emergency department (ED) patients aged 14–21 years. Participants were randomized to the intervention (Dr. Eric, Emergency Room Interventions to improve Care) or usual care. Dr. Eric consists of an ED-based sexual health app followed by 3 months of interactive text messages. We assessed the feasibility, adoption, and fidelity among users. Condom use, defined as the number of sexual encounters with condoms divided by the total number of sexual encounters over the past 4 weeks, was the primary efficacy outcome. ResultsWe enrolled 119 patients; mean age was 17.9 years, 87% were Hispanic, and half used condoms at last intercourse. Dr. Eric demonstrated feasibility, with high rates of consent (86.2%) and follow-up (81.5%). Intervention participants found Dr. Eric acceptable, liking (86.2%) and recommending (87.9%) the program. 98% of intervention participants interacted with all five app modules; one-quarter opted out of text messaging. At 6-week follow-up, the intervention group more often used a condom compared to the control group [OR 3.57, 95% confidence interval (1.93, 6.60)], p < .001]; however, this significant difference did not sustain at 13 weeks. DiscussionDr. Eric was feasible to deliver and acceptable to male AYA patients. To our knowledge, Dr. Eric is the first intervention to demonstrate evidence of short-term efficacy for improving condom use among male AYA in the ED.

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.

Efficacy and Safety of Nefecon in Patients with Immunoglobulin A Nephropathy from Mainland China: 2-Year NefIgArd Trial Results.

Immunoglobulin A nephropathy (IgAN), an immune-mediated kidney disease, is particularly prevalent among individuals of East Asian ancestry. Nefecon is a novel, oral, targeted-release budesonide formulation designed to inhibit galactose-deficient-IgA1 formation underlying IgAN pathophysiology. We present findings in patients with IgAN from mainland China participating in the 2-year, multicenter, randomized, double-blind, phase 3 NefIgArd trial of Nefecon. Patients (aged ≥18 years) with primary IgAN (estimated glomerular filtration rate [eGFR] 35-90 ml/min per 1.73 m2, persistent proteinuria [urine protein-creatinine ratio ≥0.8 g/g or proteinuria ≥1 g/24 h] despite optimized renin-angiotensin system blockade) received Nefecon or placebo over 9 months, followed by a 15-month follow-up phase on supportive care alone. The primary efficacy end point was time-weighted average of eGFR over 2 years. Sixty-two patients from mainland China were included in this prespecified analysis. The primary efficacy end point was 9.6 ml/min per 1.73 m2 (95% confidence interval [CI], 2.0 to 19.8) in favor of Nefecon versus placebo. This was consistent with (and numerically greater than) that of the global study population. Time to confirmed 30% eGFR reduction or kidney failure from baseline was substantially delayed with Nefecon (patients with an event: 9%) versus placebo (30%; hazard ratio, 0.21; 95% CI, 0.04 to 0.73]). No deaths were reported in the China cohort. In the Nefecon group, treatment-emergent serious adverse events were reported by one patient during treatment and two patients during follow-up (versus no patients and seven patients, respectively, in the placebo group). No severe infections requiring hospitalization were reported. Nefecon treatment for 9 months showed greater preservation of eGFR over 2 years compared with placebo. The efficacy outcomes were consistent with global study results, with a numerically greater treatment benefit observed in patients from China. Nefecon was well tolerated, with no unexpected safety signals.

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.

Practical application of teledentistry in orthodontic patients during the Covid-19 pandemic

Aim: Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) or COVID-19 infection has been an unusual plummet in dentistry. Various measures were adopted to slow or halt the spread of COVID-19. Many countries suspended activities that are deemed “non-essential.” Several dental procedures fall into this category, and only emergencies that cannot be postponed are still allowed. Therefore, followup visits for active orthodontic treatment should be treated with special new standard precautions. This review aims to reduce orthodontic treatment appointments by providing an overview of the available methods and their purpose in patient monitoring, i.e., teleorthodontic. Methods: A total of 5 articles demonstrating the practical application of teledentistry including teleorthodontic were included. Result: Most emergencies can be handled via teleorthodontics, which can reassure and follow patients from afar. Teleorthodontics achieved its goal of reducing patient visits while keeping regular monitoring without sacrificing results. Conclusion: Teleorthodontics can handle most emergencies assist and follow up patients remotely while at their homes. It can reduce the number of patient visits while maintaining regular monitoring without compromising the results of orthodontics treatment. These findings still need further development in efficacy, cost-effectiveness, and long-term outcomes, but we believe teleorthodontics plays an essential role during the COVID-19 outbreaks.

Impact of systemic steroids on the efficacy of first line imatinib treatment of patients with advanced gastrointestinal stromal tumors (GISTs).

Effective management of adverse events is required to maintain sufficient imatinib dosing when treating patients with gastrointestinal stromal tumors (GISTs). Skin rash is a common adverse event of imatinib, which can be effectively controlled by systemic steroid treatment without imatinib dose modification or interruption. However, the impact of the use of systemic steroids on the efficacy of imatinib treatment remains unclear. Between October 2014 and February 2022, 277 consecutive patients from a prospective registry of GIST patients were included as the study population. Patients who started systemic steroids due to grade ≥ 3 skin rash or grade 2 skin rash with grade 2 pruritis were classified as the steroid group, whereas patients who did not develop a skin rash or those who did not require steroids for a mild skin rash were classified as the control group. Efficacy outcomes were compared between the two groups. Among the 277 patients, 30 (10.8%) were treated with systemic steroids for skin rash. There was no significant difference in progression free survival (PFS) or overall survival (OS) between the steroid and control groups (3-year PFS, 67.7% vs. 65.1%, p = 0.53; 3-year OS, 91% vs. 89.9%, p = 0.67, respectively). The use of systemic steroids was not an independent factor associated with PFS (hazard ratio 0.73, 95% confidence interval 0.36-1.49, p = 0.39) and OS (hazard ratio 0.37, 95% confidence interval 0.12-1.18, p = 0.09). In the steroid group, patients who successfully maintained the imatinib dosage showed a trend toward more favorable survival outcomes than those who did not (3-year PFS, 73.3% vs. 44.4%, p = 0.34; 3-year OS, 95.8% vs. 75.0%, p = 0.15, respectively). The use of systemic steroids for the control of imatinib induced severe skin rash did not adversely affect the efficacy outcomes of imatinib in patients with advanced GIST.

The influence of partisan news on climate mitigation support: An investigation into the mediating role of perceived risk and efficacy.

Perceptions of efficacy play a central role in motivating people to engage in climate actions. However, there has been little investigation into how different climate efficacy beliefs are formed and how they may be associated with support for climate mitigation policies. This study, based on the motivated control framework, examines how risk perceptions may differentially be associated with four types of efficacy constructs (self-efficacy, personal outcome expectancy, collective efficacy, and collective outcome efficacy). It also places the motivated control framework in the context of the partisan information sphere and examines how exposure to partisan news may influence mitigation policy support through the mediators of risk perceptions and the efficacy constructs. Results suggest that liberal- and conservative-leaning news exposure, respectively, associate with higher and lower supports for policies. Overall, risk perception was a significant mediator, and the mediating function of efficacy varied depending on the specific construct being examined. For liberal news use, increased risk perceptions had a positive association with policy support through self-efficacy and collective outcome expectancy but also had an unexpected negative association with policy support through personal outcome expectancy and collective efficacy. For conservative news use, decreased risk perceptions resulted in further decreased beliefs of self-efficacy and collective outcome expectancy, resulting in lower levels of support for climate policies. We also find that political ideology is a significant moderator for the mediation model. Implications for climate change communication are discussed.

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.