Mean Reduction Research Articles

Extended course accelerated intermittent theta burst stimulation as a substitute for depressed patients needing electroconvulsive therapy.

In response to restrictions on electroconvulsive therapy (ECT) access during COVID-19, we designed a trial to assess the clinical outcomes service impacts, employing an extended course of accelerated intermittent theta burst stimulation (aiTBS), in patients with moderate to severe depression in need of ECT. This open label clinical trial was comprised of 3 phases: (i) an acute phase, where iTBS treatments were administered 8 times daily, for up to 10 days; (ii) a tapering phase of 2 treatment days per week for 2 weeks, followed by 1 treatment day per week for 2 weeks; and (iii) a symptom-based relapse prevention phase, whereby treatments were scheduled based on symptom re-emergence, for up to 6 months. Of the 155 patients who completed the acute phase of the study, the remission rate was 16.1%. The mean reduction from baseline on the HRSD-24 was 29.4% (p < 0.001) and the response rate was 25.2%. Of the 110 patients who completed the tapering phase, the mean reduction from baseline was 42.6% (p < 0.001) and response and remission rates were 49.6% and 34.8%, respectively. Of the 61 patients who were eligible for the relapse prevention phase, 43 completed, with a mean reduction from baseline of 60.1% (p < 0.001); 7 patients relapsed during this phase. This study demonstrated that an extended aiTBS protocol safely led to meaningful clinical outcomes in patients with severe depression, who otherwise would have received ECT, and thus reduced pressure on ECT services during the pandemic. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04384965 ( https://clinicaltrials.gov/study/NCT04384965?term=NCT04384965&rank=1 ).

The benefits of photobiomodulation in animal models of multiple sclerosis: a systematic review and meta-analysis

BackgroundPhotobiomodulation (PBM), using red- or near-infrared light, has been used to treat tendinopathies, nerve injuries, osteoarthritis and wounds and evaluated in experimental allergic encephalomyelitis (EAE). To date, only a few studies have been performed in EAE but surprisingly, a few clinical studies in humans have already been performed, despite the paucity of preclinical evidence.ObjectiveTherefore, this study systematically reviewed the usefulness of PBM in ameliorating the clinical signs of EAE, a commonly used animal model of multiple sclerosis, and determine if there is enough evidence to warrant human studies.MethodsPubMed, EMBASE and Web of Science were searched in July 2024 for studies relating to PBM and EAE without any language restrictions. Since only three studies have been published, all studies were included in the systematic review and data related to clinical signs of EAE was pooled together to conduct a meta-analysis. Non-homogenous data was also reported and thematically synthesized.ResultsA meta-analysis of the pooled data from the three included studies demonstrated a significant reduction of the clinical severity of EAE, with a mean reduction of 1.44, 95% CI (−2.45, −0.42), p = 0.006. PBM also significantly reduced other parameters such as infiltration of mononuclear cells, CNS demyelination, apoptosis markers and pro-inflammatory cytokines. However, there was an overall high risk of bias in all of the studies.ConclusionThe meta-analysis supports the use of PBM to ameliorate the symptoms of EAE, but the paucity of studies and the high risk of bias in the included studies warrants further preclinical investigation before conducting human studies.

Combination Resective or Ablative Epilepsy Surgery with Neurostimulation for Complex Epilepsy Networks: A Case Series

Introduction: Complex epilepsy networks with multifocal onset zones that overlap with eloquent cortex may benefit from combined surgical approaches. However, limited data exist on outcomes associated with performing these therapies in tandem. In this case series, we report on 6 patients who underwent combination surgery with either resection or laser interstitial thermal therapy (LITT) and neuromodulation with responsive neurostimulation (RNS) or deep brain stimulation (DBS). Methods: We performed a retrospective review of adult patients with medically refractory epilepsy who underwent staged combination epilepsy surgeries during the same admission at our institution. Six cases treated between 2019 and 2023 were identified. All patients underwent a presurgical work-up including invasive intracranial monitoring and underwent a combined approach with either surgical resection, LITT, RNS, or DBS. We extracted data on demographic, clinical, and surgical characteristics. The primary outcome was change in seizure frequency from baseline. Results: The mean age was 42.7 years old (4 female). All patients had at least one epileptogenic zone in the temporal lobe, two in extratemporal neocortex, two in periventricular nodular heterotopia. For the staged combination approach, 3 patients underwent LITT followed by RNS, two underwent resection and RNS, and one received LITT and DBS. The mean reduction in seizure frequency per month at last follow-up was 90%. Postoperatively, 1 patient experienced superior visual field deficits related to LITT, and another had postoperative deep vein thrombosis. Conclusion: All patients experienced at least an 83% reduction in seizures. This case series demonstrates the potential benefits of a combined surgical approach in patients with multifocal seizures and at least one lesion that can be safely resected or ablated. Future prospective studies are warranted.

Deucravacitinib, a selective, TYK2 inhibitor, in psoriatic arthritis: Achievement of minimal disease activity components in a phase 2 trial.

Deucravacitinib is a novel, oral, selective, allosteric tyrosine kinase 2 (TYK2) inhibitor belonging to a distinct class of enzyme inhibitors. In a phase 2 trial in psoriatic arthritis (NCT03881059), deucravacitinib was significantly more efficacious than placebo across multiple endpoints, including achieving minimal disease activity (MDA). This post hoc analysis further evaluated the achievement of individual components of the MDA criteria with deucravacitinib treatment and the time course of responses in the phase 2 trial. Patients (N = 203) were randomized 1:1:1 to once daily treatment with placebo, deucravacitinib 6 mg, or deucravacitinib 12 mg. The proportions of patients achieving MDA and each of the 7 individual MDA components through week 16 were assessed. At baseline, although some patients met criteria for individual MDA components, none of the patients met the composite MDA criterion, and all components were balanced overall across treatment arms. Treatment with deucravacitinib was associated with a numerically greater mean reduction from baseline in all MDA components vs placebo over 16 weeks of treatment. At week 16, a greater percentage of patients treated with either dose of deucravacitinib vs placebo achieved the threshold criteria for meeting MDA in each of the components. More patients treated with deucravacitinib met each of the MDA components vs placebo, along with a higher rate of MDA response, after 16 weeks of treatment.

Variable-RBE-induced NTCP predictions for various side-effects following proton therapy for brain tumors – Identification of high-risk patients and risk mitigation

Background and purposeDisregarding the increase of relative biological effectiveness (RBE) may raise the risk of acute and late adverse events after proton beam therapy (PBT). This study aims to explore the relationship between variable RBE (above 1.1)-induced normal tissue complication probabilities (NTCP) and patient-specific factors, identify patients at high risk of RBE-induced NTCP increase, and assess risk mitigation by incorporating RBE variability into treatment planning. Materials and methodsWe retrospectively analyzed 105 primary brain tumor patients treated with PBT (RBE = 1.1). We calculated differences in estimated NTCP (ΔNTCP) using a variable RBE-weighted dose (DRBE, Wedenberg model) and a constant RBE-weighted dose (DRBE=1.1), across 16 NTCP models. These differences were correlated with patient-specific characteristics. Based on ΔNTCP, patients were classified as high risk (32 %) or low risk (68 %) for adverse events due to RBE-induced NTCP. This classification was compared with alternative classifications based on (a) relevant patient-specific characteristics, (b) DRBE=1.1, and (c) the difference between DRBE and DRBE=1.1 (ΔD), assessing the balanced accuracy. The potential to reduce RBE-induced NTCP through track-end and linear energy transfer (LET) optimization was evaluated in six example patients. ResultsUsing a variable RBE instead of a constant one resulted in NTCP increases (up to 32 percentage points). Variable-RBE-induced NTCP increases were strongly negatively correlated with the distance between the clinical target volume (CTV) and the organ at risk (OAR) for most side-effects, and positively correlated with CTV volume for certain side-effects. High increases were associated with (a) specific patient factors, particularly the proximity of the CTV to OARs, (b) DRBE=1.1, and (c) ΔD, with a balanced accuracy of 0.88, 0.94, and 0.86, respectively. Optimization of track-ends and LET considerably reduced NTCP values, achieving a mean reduction of 31 % for optimized OARs. ConclusionThe risk of variable-RBE-induced NTCP strongly depends on patient-specific factors and the considered side-effect. A small distance between the tumor and OARs notably increases the risk. Integrating biologically-guided objectives into treatment planning can effectively mitigate the risk.

Interventions to reduce opioid use for patients with chronic non-cancer pain in primary care settings: A systematic review and meta-analysis.

This systematic review and meta-analysis aimed to assess interventions to reduce opioid use for patients with chronic non-cancer pain (CNCP) versus usual care or active controls in primary care settings. In this registered study (PROSPERO: CRD42022338458), we searched MEDLINE, Embase PsycInfo, CINAHL, and Cochrane Library from inception to December 28th 2021, and updated on Dec 14th 2023 for randomized controlled trials (RCTs) and cohort studies with no restrictions. Methodological quality was assessed using the Cochrane Risk of Bias tool for RCTs and Newcastle Ottawa Scale for cohort studies. Primary outcomes included mean reduction in morphine equivalent daily dose (reported as mean differences [MDs] mg/day; 95% confidence intervals [95%CIs]) and/or opioid cessation proportion. Secondary outcomes were mean changes in pain severity (reported as standardized mean difference [SMDs]; 95%CIs) and (serious) adverse events. Meta-analyses were performed using random-effects models. We identified 3,826 records, of which five RCTs (953 participants) and five cohort studies (901 participants) were included. Overall, opioid dosage was significantly reduced in intervention groups compared to controls (MD: -28.63 mg/day, 95%CI: -39.77 to -17.49; I2 = 31.25%; eight studies). Subgroup analyses revealed significant opioid dose reductions with mindfulness (MD: -29.36 mg/day 95%CI: -40.55 to -18.17; I2 = 0.00%; two trials) and CBT-based multimodalities (MD: -41.68 mg/day; 95%CI: -58.47 to -24.89; I2 = 0.00%; two cohort studies), respectively, compared to usual care. No significant differences were observed in opioid cessation (Odds ratio: 1.10, 95%CI: -0.48 to 2.67, I2 = 58.59%; two trials) or pain severity (SMD: -0.13, 95%CI: -0.37 to 0.11; I2 = 33.51%; three trials). Adverse events were infrequently examined, with withdrawal symptoms commonly reported. The studied interventions were effective in reducing opioid dosage for people with CNCP in primary care. They highlighted the importance of multidisciplinary collaboration. Large-scale RCTs measuring the long-term effects and cost of these interventions are needed before their implementation.

Exogenous ketones exert antiseizure effects and modulate the gut microbiome and mycobiome in a clinically relevant murine model of epilepsy.

Despite growing interest in the potential use of exogenous ketones for the treatment of epilepsy, their impact on seizures and the gut microbiome and mycobiome remain unclear. Here, we examined the effects of both oral gavage and subcutaneous (SC) injection of a ketone ester (KE) in spontaneously epileptic Kcna1-null (KO) mice that model seminal aspects of human temporal lobe epilepsy. Electroencephalographic recordings and biochemical analyses were performed in KE-treated KO mice. Fecal microbial and fungal communities were profiled to determine whether the antiseizure activity of KE involves changes in the gut microbiome. We found that exogenous KE administration by SC injection was more effective than oral gavage in terms of rendering antiseizure effects while generating similar degrees of ketonemia. However, reductions in mean daily seizure counts were accompanied by overall alterations in the fecal bacterial microbiome. Either oral or SC injection imposed a greater impact on the microbiome in male than female mice. In males, oral KE decreased Bacteroidota phylum and genera of Ligilactobacillus and Muribaculaceae, whereas SC injection decreased Bacteroides, Lactobacillus, and Lachnospiraceae. The fecal mycobiome was affected by KE injection to a greater degree than by oral gavage, and more in females than in males, as reflected by an increase in Ascomycota and Saccharomyces. Correlation analysis between microbiome and seizure counts revealed that in mice receiving KE injection, the seizure count was positively correlated with an amplicon sequencing variant of Lactobacillus (Spearman rho = .64, p = .03) and tended toward a negative correlation with Saccharomyces (Spearman rho = -.57, p = .057). Our findings demonstrate that exogenous ketone administration alone can induce antiseizure effects equally via different routes of administration, and that they induce differential shifts in both the bacterial microbiome and mycobiome.

Population Dynamic of Aphis gossypii, and Their Parasitoids, and Effect of Some Insecticides on Aphids, Chlorophyll Content, Non-Enzymatic and Antioxidant Enzymes Activity in Cantaloupe Leaves in Greenhouses

Under green house, the Population density of Aphis gossypii on cantaloupe plants recorded two peaks on May 9th and 23th with 1409 and 1561 individuals/ 10 leaves in season 2022, while one highest peak, on 16th May with 1650 individuals/ 10 leaves in season 2023. Parasitism status of Aphidius colemani and Lysiphlebus fabarum varied from 1.49% on 25 April to 35.79% on 9th of May with seasonal parasitism 2023 in 2022 and ranged between 0.73% on 25th of April and 30.06% on 16th of May with seasonal parasitism 16.57% in 2023. Acetamiprid, imidacloprid, imidacloprid + abamectin, jojoba oil, orange oil and thiamethoxam + abamectin compounds were tested to control aphids during two seasons. Imidacloprid recorded the highest reduction with all average 97.88 ±1.15 and 97.39 ±1.15 in the first and second season respectively. the highest mean reduction of emergence of the two-parasites caused by thiamethoxam + abamectin by 16.92% followed by Imidacloprid with 16.87%. While the least toxicity to emergence of the parasitoids recorded with jojoba oil 0.0% followed by orange oil 1.93% in season 2022, while in season 2023, the higher parasitoid reduction caused by acetamiprid 18.05% followed by Imidacloprid 17.69% and thiamethoxam + abamectin 17.53%. Chlorophyll content increased with treatment jojoba oil followed by Imidacloprid by 47.91 and 44.73 unit in the first season and Thiamethoxam with abamectin lead to the highest content by 44.05 unit in the leaves followed by jojoba oil with 43.65 unit. The least treatment was Imidacloprid + abamectin with 39.55 unit compared with control treatment 40.43 unit. Treatment Thiamethoxam + abamectin recorded the highest content of carbohydrates (48.43) compared with control (47.71). Treatments of insecticides led to increase of protein, fats and total lipid compared with control. Also, Antioxidant enzymes activity in cantaloupe leaves were found to be increased in the treatment of insecticides compared with control.

Emergency Department use of a high-sensitivity Point-of-Care troponin assay reduces length of stay: an implementation study preliminary report.

Point-of-care (POC) high-sensitivity troponin (hs-cTn) assays within a clinical pathway may safely reduce length of stay (LoS) for patients presenting to the emergency department (ED) with possible acute myocardial infarction (AMI). In this early-report we present the first evaluation of a POC hs-cTn in real-life care. In adult patients presenting to ED investigated for possible AMI we compared the LoS in patients assessed with a troponin in the 8-weeks before (usual-care phase) and the 8-weeks following introduction of the Siemens Atellica VTLi POC hs-cTnI for decision-making (intervention phase). The VTLi replaced the laboratory (Beckman Coulter) assay as the default hs-cTn test within the clinical pathway. This was the only change to the pathway process. The safety outcome was first event AMI or cardiac death within 30-days. There were 2376 presentations in the usual-care phase with 188 individuals with AMI and 2392 in the intervention phase with 198 AMI. In the intervention phase there was a mean (95% CI) reduction in LoS of 32 minutes (22 mins to 41 mins) compared with the usual-care phase. This represents 21.4 fewer patient-hours in the ED each day (1196 in the 8-week period). In both phases the pathway correctly identified all cases of AMI at index attendance. There were four follow-up events (2 usual-care, 2 intervention) within 30d. The deployment of a hs-cTn POC analyser into a large ED safely reduced length of stay. If translatable to other EDs this could represent an important advancement to patient care.

Efgartigimod treatment for generalized myasthenia gravis: a single-center case series of 16 patients.

Efgartigimod was approved in Japan in January 2022 for the treatment of generalized myasthenia gravis (gMG), regardless of antibody status. This case series describes a real-world experience in Japan of efgartigimod treatment for gMG patients with diverse backgrounds. We retrospectively analyzed the medical records of 16 Japanese patients (11 females and five males, mean age 40.4 years) with gMG who received efgartigimod at the Kumamoto University Hospital between August 2022 and September 2023. The outcomes were Quantitative Myasthenia Gravis (QMG) responders (≥ 3 point reduction), IgG levels, and change in prednisolone dose, in the first cycle of efgartigimod. Fifteen patients completed one cycle of efgartigimod. Of the 14 patients for whom QMG scores were obtained, 10 patients were QMG responders. Four of the five patients with Myasthenia Gravis Foundation of America class V were QMG responders. Improvement in QMG after efgartigimod treatment was observed in one patient with myasthenic crisis and in one refractory patient who had unsuccessful eculizumab treatment. The mean reductions from baseline in IgG levels at weeks 1, 2, 3, and follow-up were 38.3, 56.1, 63.1, and 43.9%, respectively. A decrease in prednisolone dose was observed in seven patients. The most common adverse events were headache (three patients) and diarrhea (two patients). One patient discontinued efgartigimod treatment due to a treatment-related adverse event of rash. Improvements in the outcomes of patients with gMG, including patients with severe gMG, myasthenic crisis, and refractory to anti-complementary therapy, were observed after the first cycle of efgartigimod treatment. Our real-world experience in Japan suggests the future possibilities for the treatment with efgartigimod for gMG with diverse backgrounds.

Long-term courses of major depressive disorder : Characteristics, risk factors and the definitional challenge of treatment response

The definition of long-term courses of depression is heterogeneous. Chronic and treatment-resistant courses, in particular, represent ahigh-cost factor and greatly reduce the quality of life. Based on the pharmacotherapeutic treatment-resistant depression (TRD), more and more systemic approaches are becoming important. This narrative review provides an overview of the long-term course of depressive disorders, including various definitions and influencing factors. In addition, an overview of biomarker research on treatment response with afocus on neuroimaging is presented. Aselective literature search was conducted in PubMed and Google Scholar for anarrative review. Particular attention was given to larger cohort studies, systematic reviews, meta-analyses and studies on the prediction of treatment response. Chronic and treatment-resistant courses mean arelevant reduction in the quality of life and increased health risks. The assessment of treatment response is adefinitional challenge: An alternative to TRD is the systemically oriented difficult to treat depression (DTD). The focus is thus moving away from symptom reduction towards controlling the level of functioning. Biomarker research for treatment response offers potential but currently mainly serves to gain theoretical knowledge. Recording the long-term course of depressive illnesses is important, but also complex. Clinical interventions should therefore include acontinuous monitoring and the focus on maintaining the quality of life.

Efficacy and Tolerability of Erenumab and Topiramate for Prevention of Chronic Migraine: A Retrospective Cohort Study

Background and Objectives: Migraine is a chronic neurological disorder affecting approximately 14% of the global population. Beyond physical pain, migraines significantly impact individuals’ quality of life, influencing education, employment, and income levels. Topiramate, a second-generation antiepileptic medication, has demonstrated notable efficacy in reducing the occurrence of chronic migraine. Over the past three decades, extensive research has implicated the neuropeptide calcitonin gene-related peptide (CGRP) in migraine pathogenesis. Erenumab, the first FDA-approved CGRP inhibitor, received approval in 2018. This study aims to compare the clinical efficacy of Erenumab and Topiramate for migraine prevention. Materials and Methods: We conducted a retrospective cohort study of adults with episodic or chronic migraine over a 12-month period, comparing Erenumab (n = 52) and Topiramate (n = 56). Outcomes assessed included changes in the Migraine Disability Assessment (MIDAS) scores from baseline over the last three months of treatment and the proportion of patients achieving a ≥50% reduction in MIDAS scores by the end of the study. Results: The Erenumab group showed significant improvement, with nearly 79% of patients achieving a 50% reduction in their MIDAS score, with a mean reduction of 3.76. Notably, only two patients (3.8.5) discontinued treatment due to adverse events. In contrast, the Topiramate group had over 15% of patients achieve a 50% reduction in MIDAS scores, with a mean reduction of 5.89, and a had discontinuation rate of 14.2% due to adverse events. Conclusions: Both Topiramate and Erenumab are effective for migraine prevention. However, Topiramate has lower tolerability and more side effects, while Erenumab offers better tolerability and safety at a higher cost. Treatment decisions should be individualized based on patient needs, efficacy, safety, and cost considerations.

Physiological adaptations of red blood cells during aestivation in the south American lungfish Lepidosiren paradoxa

The South American lungfish Lepidosiren paradoxa inhabits areas with variable pluvial regimes. During aestivation (dormancy state observed in some species during dry seasons), the prolonged period of dryness imposes osmotic stress. We aimed to investigate the physiological and morphological adaptations of RBCs in Lepidosiren paradoxa during aestivation. Here, the lungfish were subjected to aestivation for 20 and 40 days and compared to a control group in an active period. The osmotic fragility, blood osmolality, and pH were measured. Blood smears were performed to assess morphological changes in the RBCs. Lepidosiren paradoxa presented lower hemolysis when compared with a teleost fish and tegu lizard. Hemolysis increased when the lungfish was subjected to 40 days of aestivation (from 6.04 % to 16.51 %; control vs 40-day aestivation). Hematocrit rose in both aestivation groups compared to the control (26.36 %, 41.36 % and 41 %, control, 20 and 40 days, respectively; p < 0.05) indicating changes in RBC volume and hydration status. Moreover, the results revealed increased osmolality in the 40-day aestivation group (244.4 vs 372.1 mmol/Kg; control vs 40-day aestivation). 40 days of aestivation led to a decrease in blood pH when compared to the control and 20-day aestivation groups. Both aestivation durations resulted in a reduction in the perimeter and cell diameters in at least one direction of the RBCs (24 % mean reduction in size from control to 40 days aestivation). These findings suggest that South American lungfish possess remarkable physiological and morphological adaptations in their RBCs during aestivation.

AnFiS-MoH: Systematic exploration of hybrid ANFIS frameworks via metaheuristic optimization hybridization with evolutionary and swarm-based algorithms

The adaptive neuro-fuzzy inference system (ANFIS) has shown promising performance in modeling nonlinear problems, leveraging the strengths of both neural networks and fuzzy inference systems. However, as the problem scale increases, the growing number of tunable parameters in ANFIS can make it challenging to optimize via traditional gradient-based methods alone. This study introduces AnFiS-MoH, a novel framework that synergistically integrates ANFIS with metaheuristic optimization algorithms to address these challenges. By leveraging the global search capabilities of metaheuristics such as ant colony optimization (ACO), particle swarm optimization (PSO), genetic algorithm (GA), and simulated annealing (SA), ANFIS-MOH enhances the parameter tuning process of ANFIS models. We evaluate ANFIS-MOH on benchmark datasets including Boston Housing and Wine Quality, demonstrating significant improvements in prediction accuracy and generalization compared to traditional ANFIS and neural network approaches. The proposed framework achieves up to 20% reduction in Mean Squared Error and 15% increase in R2 scores, particularly excelling in handling high-dimensional, noisy data. This work contributes to the field of hybrid intelligent systems by introducing effective ways to combine the strengths of ANFIS with powerful metaheuristic optimization algorithms. The findings suggest that such hybrid approaches can be effective in tackling challenging nonlinear modeling problems. Our code is available at https://github.com/AmbitYuki/Metaheuristic-Adaptive-ANFIS.

Adjustment of stem anteversion using tapered cone stem in total hip arthroplasty.

The aim of this study was to evaluate the suitability of the tapered cone stem in total hip arthroplasty (THA) in patients with excessive femoral anteversion and after femoral osteotomy. We included patients who underwent THA using Wagner Cone due to proximal femur anatomical abnormalities between August 2014 and January 2019 at a single institution. We investigated implant survival time using the endpoint of dislocation and revision, and compared the prevalence of prosthetic impingements between the Wagner Cone, a tapered cone stem, and the Taperloc, a tapered wedge stem, through simulation. We also collected Oxford Hip Score (OHS), visual analogue scale (VAS) satisfaction, and VAS pain by postal survey in August 2023 and explored variables associated with those scores. Of the 58 patients (62 hips), two (two hips) presented with dislocation or reoperation, and Kaplan-Meier analysis indicated a five-year survival rate of 96.7% (95% CI 92.4 to 100). Mean stem anteversion was 35.2° (SD 18.2°) for the Taperloc stem and 29.8° (SD 7.9°) for the Wagner Cone stem; mean reduction from Taperloc to Wagner Cone was 5.4° (SD 18.8°). Overall, 55 hips (52 patients) were simulated, and the prevalence of prosthetic impingement was lower for the Wagner Cone (5.5%, 3/55) compared with the Taperloc (20.0%, 11/55) stem, with an odds ratio of 0.20 (p = 0.038). Among the 33 respondents to the postal survey (36 hips), the mean scores were VAS pain 10.9, VAS satisfaction 86.9, and OHS 44.7. A multivariable analysis revealed that reduction of stem anteversion from Taperloc to Wagner Cone was more favourable for VAS pain (p = 0.029) and VAS satisfaction (p = 0.002). The mid-term survival rate for THA using the Wagner Cone stem was high, which may be supported by a reduction in prosthetic impingement. The reduction in excessive stem anteversion by using a tapered cone stem was associated with reduced pain and increased patient satisfaction.

Longitudinal outcomes of iStent inject with cataract surgery compared to cataract surgery alone: real-world data from the Fight Glaucoma Blindness registry.

To compare combined phacoemulsification and iStent inject to phacoemulsification alone. Fight Glaucoma Blindness (FGB) registry - Australia. Prospective observational registry study. Eyes that had combined phacoemulsification with iStent inject (iStent group) were compared to eyes that had phacoemulsification only (cataract alone). Primary outcome was percentage of eyes achieving >20% IOP reduction from baseline 12 months after surgery. Secondary outcomes included mean IOP and medication reduction, adverse events and secondary procedures. At 12 months the percentage of eyes achieving >20% reduction of IOP at 12 months was significantly higher in the iStent group compared to the cataract alone group (40.9% vs 30.1% p<0.001). Adverse events occurred at a low rate in both groups, and secondary IOP lowering procedures were significantly less frequent in the iStent group compared to cataract alone. Real-world outcomes from the FGB registry at 12 months show phacoemulsification combined with iStent inject has higher efficacy and a reduced need for secondary IOP lowering surgery compared to phacoemulsification alone.

Deep brain stimulation of the motor thalamus relieves experimentally induced air hunger.

We previously reported that Deep Brain Stimulation (DBS) of motor thalamus (MT), in a patient with post-stroke tremor, relieved breathlessness associated with chronic obstructive pulmonary disease. This raised the question of whether MT DBS mitigates the ascending dyspnoea signal. We therefore sought to conduct a fully powered cohort study of experimentally induced air hunger (AH), an uncomfortable urge to breathe in patients with MT DBS ON and OFF. 16 patients (3 females) with DBS of the ventral intermediate nucleus (VIM) as treatment for tremor, underwent hypercapnic AH tests, with DBS "ON" and "OFF". Patients rated AH on a visual analogue scale (VAS) every 15 s. Hypercapnia and ventilation were matched for ON and OFF states (mean±sd 43±4 and 43±4 mmHg for end-tidal PCO2, 13.7 and 13.4 L·min-1 for ventilation). Participants ventilation was constrained to baseline levels by breathing from a 3-litre inspiratory reservoir with fixed flow of fresh gas while targeting their resting breathing frequency to a metronome. Overall steady state AH was 52±28%VAS for "ON" and 67±20%VAS for "OFF" (p=0.002; two-tailed paired t-test). The mean reduction in AH during VIM DBS was -14.4%VAS. MT DBS relieved AH in thirteen patients, heightened AH in two and caused no change in one. MT DBS for tremor relief also mitigates the AH component of dyspnoea. We posit that DBS of the MT heightens the gating control of the thalamus modulating the ascending air hunger signal. Extent of relief suggests that thalamic DBS may prove to be a viable therapy for intractable dyspnoea.

Quantification of construction and demolition waste disposal behaviors during COVID-19 using satellite imagery

The COVID-19 pandemic disrupted conventional municipal solid waste (MSW) management practices and affected waste generation rates. While MSW streams have been extensively studied and reported, the impact on construction and demolition (C&D) waste remains overlooked. This research develops an innovative analytical framework utilizing satellite imagery to quantify C&D waste disposal rates during COVID-19 restrictions in a mid-sized Canadian city. Supervised classification of Landsat-8 images is conducted to derive the settlement area over a period of 8.8 years (2014–2022). The C&D disposal rates and settlement area relationship is evaluated using regression analysis. Results reveal a 73.4% reduction in mean weekly C&D disposal in 2020 compared to pre-pandemic years, reflecting diminished construction activity. The settlement area exhibits a strong positive correlation (R2 = 0.812) with per capita C&D disposal rate, providing spatial evidence of urbanization patterns affecting C&D waste generation. Among socioeconomic factors examined, the value of building permits issued most influences C&D quantities (R2 = 0.934). The satellite imagery-based approach allows indirect estimation of disrupted C&D waste streams when on-site auditing is restricted during pandemics. The framework offers municipal authorities spatial decision support to formulate data-driven C&D waste management policies that are essential to smart cities and resilient to future public health emergencies.

7363 Comparing the Effectiveness of Various Insulin in Insulin Naive Type 2 Diabetes Mellitus Patients: A Study from Central India

Abstract Disclosure: K. Dash: None. S. Verma: None. U. Ayyagari: None. N. Kumari: None. A. Gwal: None. Introduction: Insulin is the cornerstone of treatment of type 2 diabetes mellitus (T2DM) and is the most efficacious treatment option. The evaluation of efficacy and safety of insulin therapy in real world setting is desirable as numerous options are currently available. This study aimed to compare the efficacy and safety of four different insulins in patients with T2DM. Methods: We conducted a retrospective observational study at our tertiary care hospital using medical records of patients with glycated hemoglobin (HbA1c) &amp;gt;8.5% who were not controlled on oral antidiabetic (OAD) medication and received add-on insulin treatment (Glargine U300, Lispro Biphasic 25/75, Glargine U100, IdegAsp). Glycemic control and incidence of hypoglycemia were analyzed from baseline to 6 months. Results: 101 patients were included. Mean age 56.4 years. 61.4% men. Mean duration of T2DM 13.3 years. 23 (22.8%), 27 (26.7%), 27 (26.7%), and 24 (23.8%) patients received Glargine U300, Lispro Biphasic 25/75, Glargine U-100, IdegAsp insulin respectively. At baseline, the mean (SD) HbA1c were 11.93% (1.85), 10.61% (1.55), 10.65% (1.59), and 10.58% (1.89) in patients receiving Glargine U300, Lispro Biphasic 25/75, Glargine U100, and IdegAsp, respectively. HbA1c, fasting plasma glucose (FPG) &amp; post-prandial plasma glucose (PPG) improved significantly from baseline to 6 months across all four treatment groups (p&amp;lt;0.001). Glargine U300 showed a significantly greater mean reduction in HbA1c by 4.57% compared to Lispro Biphasic 25/75 (3.39%; p=0.032), Glargine U100 (2.88%; p=0.004), and IdegAsp (2.38%; p&amp;lt;0.001). The mean reduction in FPG, PPG, total cholesterol and triglycerides were comparable across all four treatment groups. The mean insulin doses (SD) were 15.48 (5.65) U, 23.83 (9.49) U, 20.44 (8.76) U, and 34.17 (14.57) U at baseline and 18.89 (5.39) U, 35.52 (10.37) U, 26.07 (8.92) U, and 43.58 (15.76) at 6 months, respectively. The doses of all insulins were titrated to fasting, post-meal, or pre-dinner SMBG readings as appropriate. There were no significant changes observed in the mean body weight and insulin dose in all four subgroups. The incidence of hypoglycemia (&amp;lt;70 mg/dL and &amp;lt;54 mg/dL) was numerically lower in Glargine U300 (3 and 1) group, than in Lispro Biphasic 25/75 (8 and 5), Glargine U100 (3 and 2), and IdegAsp (7 and 3) groups. As expected, biphasic insulin had a higher numerical incidence of hypoglycemia. Conclusion: All insulins demonstrated significant improvements in glycemic parameters over the study period. However, Glargine U300 demonstrated a significantly higher reduction in HbA1c with minimal hypoglycemia events compared to other insulins and can be considered in OAD uncontrolled patients. Our results should be interpreted with caution as the study was retrospective and had a small sample size. Presentation: 6/3/2024

6814 Durability of Teprotumumab for the Treatment of Thyroid Eye Disease (TED) in Clinical Trials

Abstract Disclosure: G.J. Kahaly: Consulting Fee; Self; Amgen Inc. Research Investigator; Self; Amgen Inc. P.S. Subramanian: Consulting Fee; Self; Amgen Inc. Research Investigator; Self; Amgen Inc. E. Conrad: Employee; Self; Amgen Inc. Stock Owner; Self; Amgen Inc. R.J. Holt: Employee; Self; Amgen Inc. Stock Owner; Self; Amgen Inc. T.J. Smith: Consulting Fee; Self; Amgen Inc, Viridian, Minghui, Lassen, Lundbeck. Other; Self; US patents covering the use of IGF-1 receptor inhibitors in TED which are held by UCLA and the Lundquist Institute. Introduction: Teprotumumab has demonstrated efficacy for the treatment of thyroid eye disease (TED). To assess durability of responses to teprotumumab over the longer term, pooled clinical trial data were assessed beyond the 24-week treatment period for patients in phase 2, OPTIC, and OPTIC-X studies who received a full course of teprotumumab. Methods: Observed rates for clinical activity score (CAS, ≥2 point improvement), EUGOGO-recommended composite response, diplopia (≥1 Gorman grade improvement), proptosis (≥2 mm improvement), and Overall responder status (≥2 mm improvement proptosis and ≥2 point improvement CAS) were assessed and pooled from study baseline to Week 24 (formal study) and up to Week 72 (51 weeks post-final teprotumumab infusion). Graves’ ophthalmopathy quality-of-life (GO-QOL) scores were also examined. Additional therapies for TED administered up to Week 120 (i.e., 99 weeks post-therapy) were assessed for evidence of persistent benefit from Week 24 through Week 120. Studies differed in the timing of follow-up visits. Data were not available at every time point for all patients. Results: Response rates among patients receiving a full (8-infusion) course of teprotumumab (N=112) were largely maintained 51 weeks after the final teprotumumab infusion at study Week 72: CAS 52/57 (91.2%); composite 51/57 (89.5%); diplopia 35/48 (72.9%); proptosis 38/56 (67.9%); and Overall 37/56 (66.1%). The mean reduction in proptosis was 2.68 (SD 1.92) mm (N=56), mean GO-QOL reduction was 15.22 (SE 2.82, N=56), and disease inactivation (CAS ≤1) was detected in 40/57 (70.2%). Post-teprotumumab treatment, 17.9% (19/106) of reporting patients received additional TED treatment (systemic steroids or teprotumumab) and/or remedial periocular surgery as of 99 weeks after the last dose (to study Week 120). Conclusions: At Week 72, nearly one-year posttherapy, responses to teprotumumab were similar to those at Week 24 formal study end. Both CAS and ophthalmic composite responses were observed in 90% of observed patients. Diplopia and proptosis responses were seen in almost 70%. Additionally, 82% of patients did not require additional treatment for TED nearly two years after therapy completion. Public Presentation: 6/2/2024