Effectiveness of Botulinum Toxin Injection With Casting in Children With Spastic Cerebral Palsy: A Randomized Controlled Trial.

BACKGROUND: The most common form of movement disorder presented in children with cerebral palsy is spasticity, and dynamic equinus is the most common spastic ankle deformity. Botulinum toxin (BT) injection is now an established first-line treatment for focal spasticity. AIM: To assess the effects of BT injection with casting in the treatment of dynamic equinus in children diagnosed with cerebral palsy with spastic diplegia. SETTING AND DESIGN: A prospective randomized controlled trial was conducted among patients aged 2-12 years with cerebral palsy and spastic diplegia, attending the general outpatient department and admitted to the indoor facility of the Department of Physical Medicine and Rehabilitation and the Department of Pediatric Orthopedics at King George's Medical University, Lucknow. MATERIAL AND METHODS: Two groups of 19 patients each were formed. Group A received BT injection with casting, whereas in group B, only a cast was applied. Outcome measures including spasticity by Modified Ashworth Scale (MAS), Modified Tardieu Scale (MTS), range of motion (ROM), passive ankle dorsiflexion, and Gross Motor Function Measure (GMFM-66) (dimensions D and E) were assessed before and after the intervention. RESULTS: The participants in groups A and B were age-matched. A statistically significant difference was seen within group A and group B for MAS, passive ROM-dorsiflexion (PROM-DF), and passive ROM-plantarflexion (PROM-PF) at various follow-ups. In the 3rd week, MAS in each group was statistically insignificant (p-value> 0.05). CONCLUSION: There was a significant improvement in tone and a significant increase in the passive range of motion in both groups.

Bone Marrow Sparing by Intensity Modulated Proton Beam Therapy in Postoperative Irradiation of Gynecologic Malignancies.

Purpose: The aim of this matched-pair cohort study was to evaluate the potential of intensity-modulated proton therapy (IMPT) for sparring of the pelvic bone marrow and thus reduction of hematotoxicity compared to intensity-modulated photon radiotherapy (IMRT) in the setting of postoperative irradiation of gynaecological malignancies. Secondary endpoint was the assessment of predictive parameters for the occurrence of sacral insufficiency fractures (SIF) when applying IMPT. Materials and Methods: Two cohorts were analyzed consisting of 25 patients each. Patients were treated with IMPT compared with IMRT and had uterine cervical (n = 8) or endometrial cancer (n = 17). Dose prescription, patient age, and diagnosis were matched. Dosimetric parameters delivered to the whole pelvic skeleton and subsites (ilium, lumbosacral, sacral, and lower pelvis) and hematological toxicity were evaluated. MRI follow-up for evaluation of SIF was only available for the IMPT group. Results: In the IMPT group, integral dose to the pelvic skeleton was significantly lower (23.4GyRBE vs 34.3Gy; p < 0.001), the average V5Gy, V10Gy, and V20Gy were reduced by 40%, 41%, and 28%, respectively, compared to the IMRT group (p < 0.001). In particular, for subsites ilium and lower pelvis, the low dose volume was significantly lower. Hematotoxicity was significantly more common in the IMRT group (80% vs 32%; p = 0009), especially hematotoxicity ≥ CTCAE II (36% vs 8%; p = 0.037). No patient in the IMPT group experienced hematotoxicity > CTCAE II. In the IMPT cohort, 32% of patients experienced SIF. Overall SIF occurred more frequently with a total dose of 50.4 GyRBE (37.5%) compared to 45 GyRBE (22%). No significant predictive dose parameters regarding SIF could be detected aside from a trend regarding V50Gy to the lumbosacral subsite. Conclusion: Low-dose exposure to the pelvic skeleton and thus hematotoxicity can be significantly reduced by using IMPT compared to a matched photon cohort. Sacral insufficiency fracture rates appear similar to reported rates for IMRT in the literature.

Enhancing COVID-19 Vaccine Uptake among Tribal Communities: A Case Study on Program Implementation Experiences from Jharkhand and Chhattisgarh States, India.

Tribal populations in India have health care challenges marked by limited access due to geographical distance, historical isolation, cultural differences, and low social stratification, and that result in weaker health indicators compared to the general population. During the pandemic, Tribal districts consistently reported lower COVID-19 vaccination coverage than non-Tribal districts. We assessed the MOMENTUM Routine Immunization Transformation and Equity (the project) strategy, which aimed to increase access to and uptake of COVID-19 vaccines among Tribal populations in Chhattisgarh and Jharkhand using the reach, effectiveness, adoption, implementation, and maintenance framework. We designed a qualitative explanatory case study and conducted 90 focus group discussions and in-depth interviews with Tribal populations, community-based nongovernmental organizations that worked with district health authorities to implement the interventions, and other stakeholders such as government and community groups. The active involvement of community leaders, targeted counseling, community gatherings, and door-to-door visits appeared to increase vaccine awareness and assuage concerns about its safety and efficacy. Key adaptations such as conducting evening vaccine awareness activities, holding vaccine sessions at flexible times and sites, and modifying messaging for booster doses appeared to encourage vaccine uptake among Tribal populations. While we used project resources to mitigate financial and supply constraints where they arose, sustaining long-term uptake of project interventions appears dependent on continued funding and ongoing political support.

Efficacy of Triglyceride Glucose Index-Neck Circumference and Triglyceride Glucose Index-Neck-to-Height Ratio in the Diagnosis of Cardiovascular Diseases and Metabolic Syndrome.

BACKGROUND: A group of characteristics known as metabolic syndrome raises the chance of developing diabetes and cardiovascular disease. Insulin resistance (IR) and obesity are regarded as critical metabolic syndrome pathophysiology. OBJECTIVES: The diagnostic accuracy of IR indicators, triglyceride (TG) glucose index-neck circumference (TyG-NC), and TG glucose index-neck-to-height ratio (TyG-NHtR) to be evaluated for the detection of cardiovascular diseases and metabolic syndrome in nondiabetic individuals. MATERIALS AND METHODS: A cross-sectional study was conducted and passed by the Ethics Committee of the institute. The age should be 18 years or older, and subjects should not have diabetes. Each patient's clinical information was gathered, and lab tests were run. The study was done for a period of 1 year. RESULTS: The study has 100 participants. Around 74% of the group was women. Only 26.5% of the group had an obesity diagnosis. Poor fasting plasma glucose levels were found in 19.4% of the research team. Receiver operating characteristic (ROC)-area under the curve (AUC) testing revealed that all examined IR indices can differentiate individuals with metabolic syndrome from those who are healthy. Our analysis laid out the soaring high area under the ROC curve for TyG index and the low stunted area under the ROC curve for TyG-NC. For obesity, all indices showed appreciable diagnostic efficacy, indicating the maximum achieved area under the ROC curve for TyG index and the minimum recorded metabolic score for IR. The AUC in the case of the metabolic score for IR (METS-IR) male sample population was found to be not statistically compelling. CONCLUSION: The exploration of indirect indices, the proposed ones, namely TyG-NC and TyG-NHtR, emphasized an intricate link between cardiovascular diseases and metabolic syndrome.

Navigating the Complexities: Addressing the Challenges of Aneurysmal Atrial Septal Defects.

Aneurysmal atrial septal defects (ASDs) represent a rare subset of congenital cardiac anomalies, characterized by bulging of the interatrial septum. This condition poses unique challenges in diagnosis, management, and outcomes due to its variable clinical presentation and associated complications. While echocardiography remains the cornerstone of diagnosis, advanced imaging modalities such as cardiac magnetic resonance imaging (MRI) and computed tomography (CT) may provide additional insights. Optimal management strategies for aneurysmal ASDs require careful consideration of patient-specific factors, including the size and location of the defect, associated cardiovascular abnormalities, and the presence of pulmonary hypertension. Surgical repair, whether through conventional open-heart techniques or transcatheter interventions, remains the primary treatment modality; however, the approach may vary based on individual patient characteristics. Anesthetic considerations, including hemodynamic monitoring and perioperative care, are crucial in optimizing outcomes and reducing the risk of complications during surgical interventions. Long-term follow-up is essential to monitor potential complications such as residual shunting, arrhythmias, and the development of pulmonary vascular disease. Collaborative efforts among cardiologists, cardiothoracic surgeons, anesthesiologists, and other multidisciplinary specialists are paramount in providing comprehensive care for patients with aneurysmal ASDs.

Design and Fabrication of Broad-Spectrum Antimicrobial Porous Metallo-Polymeric Microsphere for Water Disinfection.

An expedient and efficient approach is used to synthesize a new class of metallo-polymeric microspheres (MPMs) as antimicrobials to succumb the wide range of bacteria from water. Three types of MPMs, that is, poly[Silver (I)-methacrylate-co-methylmethacrylate] (pAgMA), poly[Copper (II)-methacrylate-co-methyl methacrylate] (pCuMA), and poly[Nickel (II)-methacrylate-co-methylmethacrylate] (pNiMA), are prepared via radical suspension polymerization technique in 3D shape with porous texture. The structural and morphological characterization of the prepared microspheres are examined by analytical techniques. The antimicrobial potentialities of prepared MPMs are investigated at the laboratory scale study, revealing that the MPMs exhibit strong antibacterial activity (≈99.9% killing) against Gram-negative and Gram-positive bacteria [Enterobacter hormaechei (EH), Bacillus megatarium (BM), and Bacillus bataviensis (BB)]. The MacConkey agar medium test reveals that MPMs have substantial biocidal efficacy against broad-spectrum Gram-negative bacteria present in tap water. The MPMs exhibit significant antimicrobial efficacy via contact killing owe to the presence of integrated biocidal metal moiety, which represents that the MPMs are safe for water disinfection.

Dosimetric comparison of O-ring versus conventional C-arm linear accelerator for volumetric modulated arc therapy (VMAT) of head and neck cancer and carcinoma cervix patients.

The objective of this study is dosimetric comparison between the O-ring Halcyon and C-arm Clinac iX linac for volumetric modulated arc therapy (VMAT) plans for head & neck (H&N) cancer and carcinoma cervix patients. Total 60 patients of H&N cancer and carcinoma cervix were enrolled prospectively from March 2021 to March 2023. VMAT plans with 6 MV photons for Halcyon and Clinac iX were generated and compared for each patient by dose volume histogram for planning target volume coverage and organ at risk (OAR) sparing. There were no differences in between both the linacs for PTV D2% and D98%, homogeneity index, conformity index, Dmax (maximum dose) and Dmean (mean dose) of OAR. Halcyon had significantly shorter treatment time compared to Clinac iX. Halcyon delivered higher integral dose and monitor units. O-ring Halcyon produces VMAT plans comparable to other C-arm linacs for H&N and carcinoma cervix patients.

Pathological findings associated with the updated European Society of Cardiology 2022 guidelines for preoperative cardiac testing: an observational cohort modelling study.

BACKGROUND: In 2022, the European Society of Cardiology updated guidelines for preoperative evaluation. The aims of this study were to quantify: (1) the impact of the updated recommendations on the yield of pathological findings compared with the previous guidelines published in 2014; (2) the impact of preoperative B-type natriuretic peptide (NT-proBNP) use for risk estimation on the yield of pathological findings; and (3) the association between 2022 guideline adherence and outcomes. METHODS: This was a secondary analysis of MET-REPAIR, an international, prospective observational cohort study (NCT03016936). Primary endpoints were reduced ejection fraction (EF<40%), stress-induced ischaemia, and major adverse cardiovascular events (MACE). The explanatory variables were class of recommendations for transthoracic echocardiography (TTE), stress imaging, and guideline adherence. We conducted second-order Monte Carlo simulations and multivariable regression. RESULTS: In total, 15,529 patients (39% female, median age 72 [inter-quartile range: 67-78] yr) were included. The 2022 update changed the recommendation for preoperative TTE in 39.7% patients, and for preoperative stress imaging in 12.9% patients. The update resulted in missing 1 EF <40% every 3 fewer conducted TTE, and in 4 additional stress imaging per 1 additionally detected ischaemia events. For cardiac stress testing, four more investigations were performed for every 1 additionally detected ischaemia episodes. Use of NT-proBNP did not improve the yield of pathological findings. Multivariable regression analysis failed to find an association between adherence to the updated guidelines and MACE. CONCLUSIONS: The 2022 update for preoperative cardiac testing resulted in a relevant increase in tests receiving a stronger recommendation. The updated recommendations for TTE did not improve the yield of pathological cardiac testing.

Revolutionizing cancer treatment in India: Evaluating the unmet need, economics, and a roadmap for project implementation of particle therapy.

INTRODUCTION: This study aims to quantitatively assess eligible patients and project the demand for particle therapy facilities in India from 2020 to 2040. In addition, an economic analysis evaluates the financial feasibility of implementing this technology. The study also examines the prospective benefits and challenges of adopting this technology in India. METHODOLOGY: Cancer incidence and projected trends were analyzed for pediatric patients using the Global Childhood Cancer microsimulation model and adult patients using the Globocan data. Economic cost evaluation is performed for large-scale combined particle (carbon and proton-three room fixed-beam), large-scale proton (one gantry and two fixed-beam), and small-scale proton (one gantry) facility. RESULTS: By 2040, the estimated number of eligible patients for particle therapy is projected to reach 161,000, including approximately 14,000 pediatric cases. The demand for particle therapy facilities is projected to rise from 81 to 97 in 2020 to 121 to 146 by 2040. The capital expenditure is estimated to be only 3.7 times that of a standard photon linear accelerator over a 30-year period. Notably, the treatment cost can be reduced to USD 400 to 800 per fraction, substantially lower than that in high-income countries (USD 1000 to 3000 per fraction). CONCLUSION: This study indicates that, in the Indian scenario, all particle therapy models are cost-beneficial and feasible, with large-scale proton therapy being the most suitable. Despite challenges such as limited resources, space, a skilled workforce, referral systems, and patient affordability, it offers substantial benefits. These include the potential to treat many patients and convenient construction and operational costs. An iterative phased implementation strategy can effectively overcome these challenges, paving the way for the successful adoption of particle therapy in India. PLAIN LANGUAGE SUMMARY: In India, the number of eligible patients benefiting from high-precision particle therapy technology is projected to rise till 2040. Despite high upfront costs, our study finds the long-term feasibility of all particle therapy models, potentially offering a substantial reduction in treatment cost compared to high-income countries. Despite challenges, India can succeed with an iterative phased approach.

Discovery of CMX990: A Potent SARS-CoV-2 3CL Protease Inhibitor Bearing a Novel Warhead.

There remains a need to develop novel SARS-CoV-2 therapeutic options that improve upon existing therapies by an increased robustness of response, fewer safety liabilities, and global-ready accessibility. Functionally critical viral main protease (Mpro, 3CLpro) of SARS-CoV-2 is an attractive target due to its homology within the coronaviral family, and lack thereof toward human proteases. In this disclosure, we outline the advent of a novel SARS-CoV-2 3CLpro inhibitor, CMX990, bearing an unprecedented trifluoromethoxymethyl ketone warhead. Compared with the marketed drug nirmatrelvir (combination with ritonavir = Paxlovid), CMX990 has distinctly differentiated potency (∼5× more potent in primary cells) and human in vitro clearance (>4× better microsomal clearance and >10× better hepatocyte clearance), with good in vitro-to-in vivo correlation. Based on its compelling preclinical profile and projected once or twice a day dosing supporting unboosted oral therapy in humans, CMX990 advanced to a Phase 1 clinical trial as an oral drug candidate for SARS-CoV-2.

Alleviating summer heat stress in cowpea-baby corn intercropping with stress-reducing chemicals and fertility variations.

Over the past century, the average surface temperature and recurrent heatwaves have been steadily rising, especially during the summer season, which is affecting the yield potential of most food crops. Hence, diversification in cropping systems with suitable fertilizer management is an urgent need to ensure high yield potential during the summer season. Since intercropping has emerged as an important strategy to increase food production, the present study comprises five intercropping systems in the main plot (sole cowpea, sole baby corn, cowpea + baby corn in 2:1, 3:1, and 4:1 row ratio), three levels of fertilizer viz. 100 (N20 P40), 125 (N25 P50), and 150% (N30 P60) recommended dose of fertilizer (RDF) in the subplot, along with two stress-mitigating chemicals (0.5% CaCl2 and 1% KNO3) in the sub-sub plots. A split-split plot system with four replications was established to carry out the field experiment. The effect of intercropping, fertilizer levels, and stress-mitigating chemicals on crop growth rate (CGR), relative growth rate (RGR), plant temperature, relative water content (RWC) and chlorophyll content of cowpea and baby corn, as well as cowpea equivalent yield (CEY), was investigated during the summer seasons of 2019 and 2020. The experiment was conducted at Agriculture University, Kota (Rajasthan), India. Results showed that CGR, RGR, RWC and chlorophyll content of both crops and CEY were maximum under intercropping of cowpea and baby corn in a 2:1 row ratio compared to other intercropping systems. However, the plant temperature of both crops was significantly lower under this system. CEY, CGR, RGR, and chlorophyll content were considerably greater in the subplots with a fertilizer application of 150% RDF compared to lower levels of fertilizer (100 and 125% RDF). Our findings further show that foliar application of CaCl2 0.5% at the flowering and pod-developing stages of cowpea dramatically boosted CEY, CGR, RGR, RWC, and chlorophyll content of both crops and lowered the plant temperature.

RNA Interference With Zilebesiran for Mild to Moderate Hypertension: The KARDIA-1 Randomized Clinical Trial.

Importance: Angiotensinogen is the most upstream precursor of the renin-angiotensin-aldosterone system, a key pathway in blood pressure (BP) regulation. Zilebesiran, an investigational RNA interference therapeutic, targets hepatic angiotensinogen synthesis. Objective: To evaluate antihypertensive efficacy and safety of different zilebesiran dosing regimens. Design, Setting, and Participants: This phase 2, randomized, double-blind, dose-ranging study of zilebesiran vs placebo was performed at 78 sites across 4 countries. Screening initiation occurred in July 2021 and the last patient visit of the 6-month study occurred in June 2023. Adults with mild to moderate hypertension, defined as daytime mean ambulatory systolic BP (SBP) of 135 to 160 mm Hg following antihypertensive washout, were randomized. Interventions: Randomization to 1 of 4 subcutaneous zilebesiran regimens (150, 300, or 600 mg once every 6 months or 300 mg once every 3 months) or placebo (once every 3 months) for 6 months. Main Outcomes and Measures: The primary end point was between-group difference in least-squares mean (LSM) change from baseline to month 3 in 24-hour mean ambulatory SBP. Results: Of 394 randomized patients, 377 (302 receiving zilebesiran and 75 receiving placebo) comprised the full analysis set (93 Black patients [24.7%]; 167 [44.3%] women; mean [SD] age, 57 [11] years). At 3 months, 24-hour mean ambulatory SBP changes from baseline were -7.3 mm Hg (95% CI, -10.3 to -4.4) with zilebesiran, 150 mg, once every 6 months; -10.0 mm Hg (95% CI, -12.0 to -7.9) with zilebesiran, 300 mg, once every 3 months or every 6 months; -8.9 mm Hg (95% CI, -11.9 to -6.0) with zilebesiran, 600 mg, once every 6 months; and 6.8 mm Hg (95% CI, 3.6-9.9) with placebo. LSM differences vs placebo in change from baseline to month 3 were -14.1 mm Hg (95% CI, -19.2 to -9.0; P < .001) with zilebesiran, 150 mg, once every 6 months; -16.7 mm Hg (95% CI, -21.2 to -12.3; P < .001) with zilebesiran, 300 mg, once every 3 months or every 6 months; and -15.7 mm Hg (95% CI, -20.8 to -10.6; P < .001) with zilebesiran, 600 mg, once every 6 months. Over 6 months, 60.9% of patients receiving zilebesiran had adverse events vs 50.7% patients receiving placebo and 3.6% had serious adverse events vs 6.7% receiving placebo. Nonserious drug-related adverse events occurred in 16.9% of zilebesiran-treated patients (principally injection site reactions and mild hyperkalemia) and 8.0% of placebo-treated patients. Conclusions and Relevance: In adults with mild to moderate hypertension, treatment with zilebesiran across a range of doses at 3-month or 6-month intervals significantly reduced 24-hour mean ambulatory SBP at month 3. Trial Registration: ClinicalTrials.gov Identifier: NCT04936035.

Resistance analysis following sotrovimab treatment in participants with COVID-19 during the phase III COMET-ICE study.

Aim: Sotrovimab is an engineered human monoclonal antibody that binds a conserved region of the SARS-CoV-2 spike protein. The COMET-ICE phase III study evaluated sotrovimab for treatment of mild to moderate COVID-19 in nonhospitalized participants with ≥1 risk factor for severe disease progression. Materials & methods: We evaluated the presence of circulating SARS-CoV-2 variants of concern or interest (VOCs/VOIs) and characterized the presence of baseline, post-baseline and emergent amino acid substitutions detected in the epitope of sotrovimab in SARS-CoV-2. Results: None of the sotrovimab-treated participants with baseline epitope substitutions, and 1 of 48 sotrovimab-treated participants with post-baseline epitope substitutions, met the primary clinical endpoint for progression. Conclusion: Overall, progression was not associated with identified VOC/VOI or the presence of epitope substitutions in sotrovimab-treated participants.

Analysis of the genetics of the SARS-CoV-2 virus from participants in a clinical study for treatment of COVID-19 In a large clinical study, the ability of the monoclonal antibody sotrovimab to treat patients with mild to moderate COVID-19 was looked at. This paper focuses on the genetics of the SARS-CoV-2 viruses from participants in this clinical study. Overall, most participants in the study were infected with the original 'wild type' variant of SARS-CoV-2. We also looked for changes in the virus at the positions on the viral spike protein where sotrovimab binds. In participants treated with sotrovimab, changes in the virus at the site where sotrovimab binds on the viral surface protein were not associated with negative outcomes in participants. Clinical Trial Registration: NCT04545060 (ClinicalTrials.gov).

Assessment of symptoms in COMET-ICE, a phase 2/3 study of sotrovimab for early treatment of non-hospitalized patients with COVID-19.

BACKGROUND: The COMET-ICE trial demonstrated that sotrovimab clinically and statistically significantly reduces the risk of all-cause > 24-h hospitalization or death due to any cause among patients with COVID-19 at high risk of disease progression. Patient-reported outcomes are important to capture symptom burden of COVID-19 and assess treatment effectiveness. This study investigated symptoms and their impact over the acute phase of COVID-19 infection among patients on sotrovimab versus placebo. METHODS: Randomized (1:1), double-blind, multicenter, placebo-controlled, phase 2/3 study in 57 centers across five countries. Participants were non-hospitalized patients with symptomatic, mild-to-moderate COVID-19 and ≥ 1 baseline risk factor for disease progression (aged ≥ 55 years or ≥ 1 of the following: diabetes requiring medication, obesity, chronic kidney disease, congestive heart failure, chronic obstructive pulmonary disease, or moderate-to-severe asthma). An intravenous infusion of sotrovimab 500 mg or placebo was administered on Day 1. The FLU-PRO Plus questionnaire was administered once-daily with 24-h recall from Day 1-21, and at Day 29. Intensity and duration of COVID-19 symptoms were determined from area under the curve (AUC) and mean change in total and individual domain scores through Days 7, 14, and 21. Time to symptom alleviation was assessed. RESULTS: In total, 1057 patients were randomized to sotrovimab (n = 528) or placebo (n = 529). At Day 7, mean decrease in FLU-PRO Plus total score (measured by AUC) was statistically significantly greater for patients on sotrovimab (-3.05 [95% confidence interval (CI) -3.27 to -2.83]) than placebo (-1.98 [95% CI -2.20 to -1.76]; difference -1.07 [95% CI -1.38 to -0.76]; p < 0.001). Significant differences were also observed at Days 14 and 21. A more rapid decline in symptom severity was observed with sotrovimab versus placebo through Week 1 and the first 21 days post-treatment. By Day 21, 41% of patients on sotrovimab and 34% on placebo reported symptom resolution. In a post-hoc analysis, median time to symptom alleviation was 4 and 6 days, respectively. CONCLUSIONS: Sotrovimab provides significant and rapid improvements in patient-reported COVID-19 symptoms, as measured by the FLU-PRO Plus. These results further show the benefits of sotrovimab in alleviating symptoms among high-risk patients with COVID-19. Trial registration ClinicalTrials.Gov: NCT04545060 ( https://clinicaltrials.gov/ct2/show/NCT04545060 ). Date of registration: September 10, 2020 (retrospectively registered).

Construction of arsenic selective chelating resin with iron precursor for removal of low-concentration arsenic: Breakthrough modeling and field deployment.

The presence of exorbitant arsenic contamination in the aquatic environment causes astronomically immense health quandaries affecting millions of people, which may lead to death in the case of prolonged indigestion of arsenic-containing drinking water. Herein, we are reporting porous chelating resin with an iron precursor for the removal of arsenic ions from water. Weak acid cation resin was functionalized under varying experimental conditions to get a suitable resin with high arsenic uptake. The theoretical results revealed that the maximum Langmuir adsorption capacities of 3.27 mg g-1 and 1.13 mg g-1 were achieved for As(V) and As(III), respectively. The kinetics of adsorption followed the pseudo-second-order (PSO) model with a high determination coefficient (R2) of 0.9963 and 0.9895 for As(V) and As(III), respectively. The Adams-Bohart, Thomas, Yoon-Nelson, and Pore diffusion models were used to identify the breakthrough curve in the fixed bed adsorption column. The column performance improved with a larger bed height (55 cm), low concentration of influent (0.25 mg L-1), and low flow rate of influent (80 mL min-1). Under this condition, the breakthrough time and exhaustion time were 314 min and 408 min for As(V) and 124 min and 185 min for As(III), respectively.

A pilot phase 2a, randomized, double-blind, placebo-controlled study to explore the antiviral activity, clinical outcomes, safety, and tolerability of rilematovir at two dose levels in non-hospitalized adults with respiratory syncytial virus infection.

OBJECTIVES: To assess the antiviral effect, clinical outcomes, and safety of the respiratory syncytial virus (RSV) fusion inhibitor rilematovir in non-hospitalized RSV-infected adults. METHODS: This phase 2a, double-blind, multicentre study randomly assigned RSV-positive adult outpatients ≤5 days from symptom onset 1:1:1 to receive rilematovir 500 mg, 80 mg, or placebo once-daily for 7 days. Antiviral effect was assessed by RSV RNA viral load (VL), measured by quantitative RT-PCR, and Kaplan-Meier (KM) estimates of time to undetectable VL. Clinical course was assessed by KM estimates of median time to resolution of key RSV symptoms assessed through patient-reported outcomes. RESULTS: RSV-positive patients (n = 72) were randomly assigned; 66 had confirmed RSV infection and received rilematovir 500 mg (n = 23), 80 mg (n = 21) or placebo (n = 22). Differences versus placebo in mean RSV RNA VL area under the curve (90% CI) through days 3, 5 and 8, respectively, were 0.09 (-0.837; 1.011), -0.10 (-2.171; 1.963), and -1.03 (-4.746; 2.682) log10 copies.day/mL for rilematovir 500 mg, and 1.25 (0.291; 2.204), 2.53 (0.430; 4.634), and 3.85 (0.097; 7.599) log10 copies.day/mL for rilematovir 80 mg. KM estimates of median (90% CI) time-to-first confirmed undetectable VL were 5.9 (3.85; 6.90), 8.0 (6.86; 12.80) and 7.0 (6.62; 10.88) days and 5.7 (2.93; 7.01), 8.1 (6.74; 12.80) and 7.9 (6.62; 11.74) days in patients with symptom onset ≤3 days, for rilematovir 500 mg, 80 mg, and placebo, respectively. KM estimates of median (90% CI) time to resolution of key RSV symptoms were 7.1 (5.03; 11.43), 7.6 (5.93; 8.32), and 9.6 (5.95; 14.00) days for rilematovir 500 mg, 80 mg, and placebo, respectively; and in patients with symptom onset ≤3 days, median 8.0, 7.6, and 11.8 days, respectively. DISCUSSION: Rilematovir use, initiated early, suggests a potential clinical benefit in RSV-infected adults, with data supporting development of RSV therapeutic options. TRIAL REGISTRATION: This study is registered with clinicaltrials.gov (NCT03379675).

A prospective study to assess and quantify the setup errors with cone-beam computed tomography in head-and-neck cancer image-guided radiotherapy treatment.

Introduction: This study was done to quantify the translational setup errors with cone-beam computed tomography (CBCT) in the image-guided radiation therapy (IGRT) treatment of head-and-neck cancer (HNC) patients. Aims: The objective was to quantify the setup errors by CBCT. Methodology: One hundred patients of HNC were enrolled from March 2020 to March 2021 for IGRT treatment. Pretreatment kV-CBCT images were obtained at the first 3 days of irradiations, and setup error corrections were done in the mediolateral (ML), superior-inferior (SI), and anterior-posterior (AP) directions. Subsequently, a weekly kV-CBCT was repeated for whole duration of radiotherapy for the next 6-7 weeks. Adequacy of planning target volume (PTV) margins was assessed by van Herk's formula. Results: Total 630 CBCT scans of 100 patients were analyzed. Setup errors greater than 3 mm and 5 mm were seen in 11.4% and 0.31% of the patients, respectively. Systematic errors and random errors before correction in ML, SI, and AP directions were 0.10 cm, 0.11 cm, and 0.12 cm and 0.24 cm, 0.20 cm, and 0.21 cm, respectively. Systematic errors and random errors after correction in ML, SI, and AP directions were 0.06 cm, 0.07 cm, and 0.07 cm and 0.13 cm, 0.10 cm, and 0.12 cm, respectively. Conclusion: CBCT at the first 3 fractions and then weekly during radiotherapy is effective to detect the setup errors. An isotropic PTV margin of 5 mm over clinical target volume is safe to account for setup errors, however, in the case of close organ at risk, or with IGRT, a PTV margin of 3 mm can be considered.