Open Label Research Articles

The use of a surgical procedure manager in open liver surgery - an open label RCT

The use of a surgical procedure manager in open liver surgery - an open label RCT

Longitudinal follow-up of metformin treatment in Fragile X Syndrome.

Metformin has been used as a targeted treatment to potentially improve cognition and slow the typical IQ decline that occurs during development among individuals with fragile X syndrome (FXS). In this follow-up study, we are following the trajectory of IQ and adaptive behavior changes over 1 to 3 years in individuals with FXS who are clinically treated with metformin in an open label trial. Individuals with FXS ages 6 to 25 years (mean 13.15 ± 5.50) and nonverbal IQ mean 57.69 (±15.46) were treated for 1-3 years (1.88 ± 0.63). They all had a baseline IQ test using the Leiter-III non-verbal cognitive assessment and the Vineland-III adaptive behavior assessment before the start of metformin. Repeat Leiter-III and Vineland-III were completed after at least 1 year of metformin (500-1,000 mg/dose given twice a day). There were no significant changes in non-verbal IQ or in the adaptive behavior measurements at FDR < 0.05. The findings thus far indicate that both IQ and adaptive behavior are stable over time, and we did not see a significant decline in either measure. Overall, the small sample size and short follow-up duration limit the interpretation of the effects of metformin on cognitive development and adaptive functioning. There is individual variability but overall for the group there was no significant decline in IQ or adaptive behavior.

Comparison of Doppler Guided Seldinger Technique Versus Classic Palpatory Seldinger Technique for Radial Artery Cannulation-an Open Label Randomized Controlled Trial

Objective: Radial artery cannulation is commonly performed by the conventional palpatory technique. However, in circumstances where the cannulation is difficult, other methods such as Doppler or ultrasound are used to guide the cannulation. Incorporating the Seldinger technique can further improve the successful cannulation. The aim of the study was to compare the first attempt success rate of radial artery cannulation between conventional palpatory Seldinger technique and Doppler guided Seldinger technique. Methods: Ninety patients undergoing major open abdominal surgeries were divided into two groups -the Classic palpatory and the Doppler guided radial artery cannulation. The Seldinger Technique was used in both the groups. First attempt success rate of radial artery cannulation and time to cannulation were noted by both the techniques. Results: The number of attempts and the time to cannulation were significantly less in the palpatory Seldinger group as compared with the Doppler Seldinger group. Complication rates were similar in both the groups but there were 4 failure in palpatory Seldinger group. Conclusion: The classic palpatory technique along with the Seldinger technique for radial artery cannulation is better in terms of first attempt cannulation rate and duration of cannulation than the Doppler guided Seldinger technique in patients undergoing elective surgeries. However, Doppler method had no failures and can be a useful rescue method in failed cannulation.

Additional Bicarbonate Infusion Complements WHO Rehydration Therapy in Children with Acute Diarrhea and Severe Dehydration Presenting with Severe Non-anion Gap Metabolic Acidemia: An Open Label Randomized Trial.

To assess the efficacy and safety of bicarbonate infusion in children with Acute Diarrhea and Severe Dehydration (ADSD) having severe Non-Anion Gap Metabolic Acidemia (sNAGMA). Children (aged 1-144 mo) with ADSD and sNAGMA (pH ≤7.2 and/or serum bicarbonate ≤15mEq/L) were enrolled in an open-label randomized design. Controls (n = 25) received WHO-recommended rehydration therapy with Ringer Lactate, while intervention group (n = 25) received additional bicarbonate deficit correction. Primary outcome was time taken to resolve metabolic acidemia (pH >7.30 and/or bicarbonate >15mEq/L). Secondary outcome measures were adverse outcome [composite of pediatric intensive care unit (PICU) transfer and deaths], acute care area free days in 5 d (ACAFD5), hospital stay, and adverse effects. Time taken to resolve metabolic acidemia was significantly lesser with intervention [median (IQR); 8h (4, 12) vs. 12h (8, 24); p = 0.0067]. Intervention led to acidemia resolution in significantly more children by 8h and 16h (17/25 vs. 9/25, p = 0.035 and 23/25 vs. 17/24, p = 0.018, respectively). Patients with fluid refractory shock needed lesser inotropes in intervention group [median Vasoactive Inotrope Score (VIS), 10.5 vs. 34]. Intervention led to significantly lesser adverse outcome (0/25 vs. 5/25, p = 0.049), and noticeably more ACAFD5 [median (IQR); 2 (1, 2) vs. 1 (1, 2); p = 0.12]. Two patients died in the control group while none in the intervention group. No adverse effect was documented. Additional calculated dose of bicarbonate infusion led to significantly early resolution of metabolic acidemia, lesser utilization of critical care facilities, and lesser adverse outcome in children with ADSD and sNAGMA, compared to standard therapy, with no adverse effect.

Comparison between the effect of Empagliflozin and Pioglitazone added to metformin in patients with type 2 diabetes and nonalcoholic fatty liver disease

Background/aimsNon-alcoholic fatty liver disease (NAFLD), defined as the accumulation of >5% fat in the liver, is the most frequently co-exist disease with diabetics up to 70%. Current study was conducted to compare efficacy of combination therapy of empagliflozin (EMPA) or pioglitazone (PGZ) with metformin (MET) in patients with T2DM and NAFLD. MethodsIn this open label, prospective clinical trial, sixty patients were randomly assigned to receive EMPA 10 mg/day or PGZ 30 mg/day in combination Metformin (at least 1500 mg) for six months. NAFLD grade and liver stiffness were defined and measured at the beginning and after 6 months. As the secondary outcomes, anthropometric characteristics, lipid profile, plasma glucose test, and liver enzymes test were measured at the baseline and endpoint. ResultsThe results showed that both combination therapy with EMPA+ MET or PGZ+MET significantly reversed fibrosis stage of NAFLD (P<0.05). Significant reduction in lipid profile test, and liver enzymes test were seen in both groups (P<0.05). However, the greater reduction in waist circumference was observed in EMPA groups compared to PGZ (-4.4 ± 2.39 vs -2.05±1.28, p<0.001), meanwhile weight and BMI decreased significantly only in the patients receiving EMPA (-5.78 ± 3.6 kg vs 0.93 ± 0.33 kg and -2.01± 3.19 kg/m2 vs 0.33 ± 0.12 kg/m2, respectively, P<0.001). Conclusioncombination of EMPA or PGZ with metformin equally improved liver fibrosis stage and stiffness in T2DM patients with NAFLD. The improvements of laboratory tests were observed in the both groups, while, regarding weight reduction, only the regimen containing EMPA was effective.

Mediterranean Diet, Vitamin D, and Hypercaloric, Hyperproteic Oral Supplements for Treating Sarcopenia in Patients with Heart Failure-A Randomized Clinical Trial.

Malnutrition and sarcopenia frequently affect patients with heart failure (HF), in which clinical outcomes and survival is decreased. Thus, appropriate nutritional screening and early nutrition support are highly recommended. Currently, nutritional support is not a standard of care in patients with HF, and the use of commercially available oral supplements (OSs) could provide an additional benefit to medical treatment in these patients. To compare the effect of the Mediterranean diet in combination with hypercaloric, hyperproteic OS in patients with HF. An open label, controlled clinical study in which patients were randomly assigned to receive a Mediterranean diet (control group) vs. hypercaloric, hyperproteic OS (intervention group) for twenty-four weeks. Thirty-eight patients were included; epidemiological, clinical, anthropometric, ultrasound (muscle echography of the rectus femoris muscle of the quadriceps and abdominal adipose tissue), and biochemical evaluations were performed. All patients received additional supplementation with vitamin D. Baseline malnutrition according to the GLIM criteria was observed in 30% of patients, while 65.8% presented with sarcopenia. Body cell mass, lean mass, and body mass increased in the intervention group (absolute increase of 0.5, p = 0.03, 1.2 kg, p = 0.03, and 0.1 kg, p = 0.03 respectively). In contrast, fat mass increased in the control group (4.5 kg, p = 0.05). According to the RF ultrasound, adipose tissue, muscle area, and circumference tended to decrease in the intervention group; it is probable that 24 weeks was too short a period of time for evaluating changes in muscle area or circumference, as previously observed in another group of patients. In contrast, functionality, determined by the up-and-go test, significantly improved in all patients (difference 12.6 s, p < 0.001), including the control (10 s improvement, p < 0.001) and the intervention group (improvement of 8.9 s, p < 0.001). Self-reported QoL significantly increased in all groups, from 68.7 ± 22.2 at baseline to 77.7 ± 18.7 (p = 0.01). When heart functionality was evaluated, LVEF increased in the whole cohort (38.7 ± 16.6 vs. 42.2 ± 8.9, p < 0.01); this increase was higher in the intervention group (34.2 ± 16.1 at baseline vs. 45.0% ± 17.0 after 24 weeks, p < 0.05). Serum values of NT-proBNP also significantly decreased in the whole cohort (p < 0.01), especially in the intervention group (p = 0.02). After adjusting by age and sex, nutritional support, baseline LVEF, NT-proBNP, and body composition parameters of functionality tests were not associated with mortality or new hospital admissions in this cohort. Nutritional support with hypercaloric, hyperproteic OS, Mediterranean diet, and vitamin D supplementation were associated with decreased NT-proBNP and improvements in LVEF, functionality, and quality of life in patients with HF, despite a significant decrease in hospital admissions.

An Analysis of the VELNEZ Nasal Pack's Acceptability and Safety for Use During Nasal Surgery: A Prospective Study.

The primary function of nasal packs is to modulate the bleeding, prevent adhesions and obstruction, with least discomfort to the subjects without risking secondary infection. However, both packing and removal of the pack is an unpleasant experience, with the latter being extremely painful. Therefore the need of the hour is a dressing which prioritizes subject comfort without compromising other desired nasal pack properties.Twenty subjects were enrolled in this interventional, open label study. The subjects had 10 hospital visits, starting from baseline (Visit 1) to postoperative day 28 (Visit 10), at regular intervals. The proportion of the population with postoperative pain alleviation and bleeding control failure (within 10min) were the main objectives. Within 10min of VELNEZ administration, all 20 participants got their bleeding under control. With VELNEZ, the painful nasal pack removal method was totally avoided because it was biodegradable. No moderate/severe pain, infection and adhesions were reported in any of the subjects, but few subjects reported moderate obstruction until Visit 3 (Discharge Day). In the present study, for participants undergoing nasal surgery, VELNEZ proved to be a secure and reliable nasal pack. Trial Registration: CTRI/2021/09/036437, prospectively registered.

How do Employees Experience Digital Monitoring and Coaching to Better Cope with Their Pain: A Pilot Study with a Smartphone Application

Background: Pain complaints are an important problem for employees, employers, and society. Up to 60% of the working population suffers from pain and these complaints are responsible for a third of all absenteeism. Pain is a complex phenomenon influenced by physical and psychosocial factors. Digital technologies such as smartphone applications offer opportunities to empower employees and help them manage and cope with their pain. However, lack of empirical evidence and user-friendly design hinder the adoption of these technologies in practice. This one group open label pilot aimed at evaluating the impact and user experience of an innovative smartphone application that includes monitoring as well as coaching to help employees manage their pain.&#x0D; Methods: An extensive co-design process including 262 end-users and seven domain experts was used to develop an app that contains 1) a monitoring part with questionnaires and integration with an activity tracker and 2) a coaching part including online information and exercises to help improve pain-related cognitions and other pain-management skills. Afterwards, 66 employees (experiencing pain for at least six weeks) of a large Belgian hospital used the smartphone app for six months. Every six weeks, participants were asked to complete a standardized questionnaire measuring work expectations, pain-related perceptions, and pain behavior. Finally, 12 employees participated in a semi-structured interview to help understand the quantitative findings, evaluate the user experience, and formulate recommendations towards the use of pain-management apps for employees. Quantitative and qualitative analyses by means of SPSS (version 28.0.1.0) and NVivo (version 1.0) were conducted to test the hypotheses. &#x0D; Results: Forty-eight participants had complaints, mostly located in the back (80%) and neck (74%), for at least one year. Only pain catastrophizing (χ2=15.934, p = .001) and fear avoidance (χ2=8.934, p = .030) were improved after using the app for six months. Participants experienced the app as useful and well elaborated. Based on the thematic analysis, seven recommendations emerged: 1) awareness and education about pain and pain perceptions stimulates behavior change, but make sure that the focus is on coping with pain and valued activities and not on the pain itself, 2) monitoring should be user friendly, accurate, and relevant, 3) the ability to explore and learn at your own pace is a must, 4) app functionalities should be attractive and provide maximal reward while requiring minimal effort from the user, 5) personalized and job-specific content is a must, 6) a blended approach, i.e. digital tools combined with human contact with a professional expert, is recommended, and 7) integration within a broader well-being policy at work is required.&#x0D; Conclusion: A smartphone application may help employees to monitor and cope with their pain at work. Provided that it meets some specific requirements: 1) an app is not used as a standalone but integrated within a broader wellbeing policy at work, 2) there is the possibility to interact with a professional, and 3) an app contains personal and job-specific recommendations tailored to the workplace and specific needs of the user.

An Open Label Single Arm Clinical Study on Dashamooladi Yamaka Pratimarsha Nasya and Ashtavargam Kashaya in Vishwachi (Cervical Radiculopathy)

Background: Vishwachi is one among the 80 Vatavyadhi. Lakshana of Vishwachi are Bahu Cheshtapaharana, Bahu Karma Kshaya, Stambha, Ruja, Toda, Spandana, Tandra, Gourava and Arochaka. Cervical radiculopathy is a condition similar to Vishwachi, which results from compression of cervical nerve roots. This leads to neck pain radiating along the distribution of the affected nerve root, numbness, altered reflexes and weakness in the muscles of arm. Objectives: To evaluate the combined effectiveness of Dashamooladi Yamaka Pratimarsha Nasya and Ashtavargam Kashaya in Vishwachi (Cervical Radiculopathy). Materials and methods: 30 subjects fulfilling the inclusion criteria were administered with Dashamooladi Yamaka Pratimarsha Nasya in the dose of 2 Bindu twice daily after food and Ashtavargam Kashaya, 15ml thrice daily after food, for 14 days. Ruja, Toda, Spandana, Sthambha, Tandra, Gourava, Arochaka, Bahukarmakshya, Bahucheshtapaharana and Spurling test were assessed on 1 st day, 7th day and 15th day. Data were analyzed using appropriate statistical tests. Results and conclusion: Statistically significant (P &lt; 0.05) improvement was observed in symptoms such as Bahu Karmakshaya, Bahu Cheshtapaharana, Ruja, Toda, Spandana and range of cervical movement. Dashamooladi Yamaka Pratimarsha Nasya and Ashtavargam Kashaya were found to be effective in the management of Vishwachi.

An open label single arm clinical study to evaluate the combined effectiveness of Navakashaya and Vidangadi Lepa in Vicharchika (Dermatitis)

Background: Vicharchika is one among the Kshudra Kushta with predominance of Kapha Dosha and it is characterized by, Kandu (Itching), Bahu Srava (Excessive exudation), Shyava Varna (Greyish black discolouration) and Pidaka (Papule). Vicharchika is similar to Dermatitis (Eczema). Dermatitis is a heterogenous group of disorders that share similarities in clinical appearance and histopathologic findings, but may have different etiologies. Objectives: To evaluate the combined effectiveness of Navakashaya and Vidangadi Lepa in the management of Vicharchika (Dermatitis). Methods: Among 34 registered subjects, 30 of them completed the course of treatment. They were administered with Navakashaya internally and Vidangadi Lepa application externally for a period of 30 days. Ordinal data was analyzed with Friedman’s test followed by Wilcoxon signed rank test as post-hoc and Nominal data was analyzed with Cochran Q test followed by McNemar test as post-hoc. Continuous data was analyzed by Repeated Measures ANOVA and after applying bonferroni correction with Paired t test as post-hoc. Results: There was statistically significant improvement in the subjective and objective parameters of Vicharchika (Dermatitis). Conclusion: Navakashaya and Vidangadi Lepa are effective in the management of Vicharchika (Dermatitis).

Comparative assessment of immunogenicity of recombinant insulin Aspart from BioGenomics and its originator NovoRapid® in adult patients with type 2 diabetes mellitus.

To assess and compare the immunogenicity of recombinant Insulin Aspart [manufactured by BioGenomics Limited (BGL-ASP)] with its originator NovoRapid® (manufactured by Novo Nordisk) in adult patients with type 2 diabetes mellitus. BGL-IA-CTP301 study was a randomized, open label, parallel group, multicenter phase-III clinical study to compare the efficacy and safety of recombinant Insulin Aspart 100U/mL [manufactured by BioGenomics Limited (BGL-ASP)] with its reference medicinal product (RMP); NovoRapid® [manufactured by Novo Nordisk], in adult patients with Type 2 diabetes mellitus(T2DM). The primary objective of the study was to compare the immunogenicity of BGL-ASP and RMP; NovoRapid® in patient serum samples collected from phase-III clinical study. Immunogenicity was studied as the incidence of patients positive for anti-insulin Aspart (AIA) antibodies, developed against BGL-ASP/RMP at baseline, end of 12week and end of 24week of the treatment period. The changes in incidence of patients positive for AIA antibodies post-baseline were also studied to assess and compare the treatment-emergent antibody response (TEAR) between the treatment groups (BGL-ASP and RMP). Statistical evaluation was done by Fisher's exact test to compare the overall incidence of patients positive for AIA antibodies and the TEAR positives observed post-baseline in both the treated groups. An in-vitro neutralizing antibody assay (Nab assay) was also performed to study the effect of AIA antibodies in neutralizing the biological activity/metabolic function of the insulin. The neutralizing potential of AIA was studied by its effect on %glucose uptake. We also evaluated the association between AIA antibody levels and its impact on biological activity by studying the correlation between them. Analysis of immunogenicity data suggested that the percentage of patients positive for AIA antibodies until week 24 was similar and comparable in both the treatment groups, BGL-ASP and RMP; NovoRapid®. The changes in incidence of patients positive for AIA post-baseline in terms of TEAR positives were also similar and comparable between the treatment groups. The results of the Nab assay with confirmed positive AIA samples from BGL-ASP- and RMP-treated groups did not have any negative impact on %glucose uptake by the cells in Nab assay, confirming the absence of neutralizing antibodies in both the treatment groups. The correlation studies also showed absence of association between AIA antibody levels and percentage glucose uptake in both BGL-ASP and RMP-NovoRapid® treatment groups. CONCLUSIONS: The immunogenicity assessment based on the overall incidence of patients positive for AIA, changes in incidence of patients positive for AIA post-baseline, TEAR rates and absence of neutralizing antibodies, were found to be apparently similar and comparable in both the treatment groups (BGL-ASP and RMP). We conclude from our studies that the immunogenicity of BGL-ASP is similar and comparable to RMP and the observed immunogenicity in terms of anti-insulin Aspart antibody levels had no impact on the biological activity of insulin.

Research hotspots and frontiers in acral melanoma: A bibliometric analysis from 1999 to 2023

BackgroundAcral melanoma (AM), an aggressive subtype of melanoma with poor prognosis, has been increasingly studied. The present study aims to discuss the current status, hotspots and future directions of AM studies through visualized analysis with bibliometrics and knowledge graph. MethodPublications related to acral melanoma from January 1999 to May 2023 were searched and retrieved from the Web of Science. Data extraction and visualization of the top 10 publications by year of publication, journal, country and core author were performed using R Studio (Version 4.3.0) and Scimago Graphica (Version 1.0.34). Co-reference graphs regarding country/region, organization, author, and keywords, as well as reference collaborative network, co-occurrence network, and references were plotted using VOSviewer (Version 1.6.19) and CiteSpace (Version 6.2.R3). ResultsA total of 1387 articles related to AM published in English from 1999 to 2023 were included in the present study. A total of 7499 authors were from 2092 organizations in 50 countries. The articles were published in 356 journals, involving 4131 keywords and 28,200 references. The 1387 articles related to AM had been cited a total of 10,014 times by the time of this study. The result showed that Journal of the American Academy of Dermatology had the largest number of citations and citation rate, with a total of 60 publications having been cited 2191 times. Having the top three productivity institutions in the world, the US is the most productive country in this field, with a total of 361 publications. The authors with the highest number of publications were Guo Jun (n = 43) and Si Lu (n = 38) from Peking University. The keyword burstiness test found that “ipilimumab”, “open label”, “efficacy” and “nivolumab” appeared most frequently in recent years. The co-cited reference timeline graph showed that the clustering of “advanced melanoma” and “melanocytic lesion” has been a hotspot since 2016. ConclusionsThe number of AM-related studies has been increasing. The clinical characteristics and immunotherapy of AM are still key research directions, with the US playing a leading role in this field. This bibliometric analysis found up to 1387 publications, which not only comprehensively and quantitatively reflected the research trends and hotspots, but also provided a theoretical basis for future studies of AM. Researchers can benefit from choosing the right journals and finding potential collaborators or partner institutions.

Transcranial focused ultrasound for the treatment of tremor: A preliminary case series

BackgroundEssential tremor (ET) can be debilitating. Treatments for ET include beta-blockers and surgical interventions. Low-intensity focused ultrasound (LIFU) may offer an office-based non-invasive alternative. ObjectiveThis pilot open label clinical trial explores safety, feasibility, and potential efficacy of LIFU in treatment of ET. MethodsWe report outcomes from the first 10 participants in this IRB-approved trial of LIFU for treatment of ET. The ventral intermediate nucleus of the thalamus (Vim) was targeted using structural and functional MRI. Participants underwent eight 10-min sessions of LIFU targeting the contralateral (Vim) to the most affected hand. Safety was closely monitored; Global Rating of Change (GRC) and The Essential Tremor Rating Scale (TETRAS) scores were collected. ResultsNo adverse effects were reported. Eight participants reported a GRC ≥2. TETRAS performance subscale demonstrated clinically significant improvement in all participants. ConclusionPreliminary findings support LIFU's safety and feasibility. The potential efficacy encourages additional sham-controlled studies.

Comparison of Trans-Resveratrol (98% Pure) with Resveratrol (40%) as Rejuvenation Therapy on Ovarian Reserve Parameters and Pregnancy Outcomes in Infertile Adult Women with Poor Ovarian Reserve, Undergoing Assisted Conception Cycles – A Double Arm, Randomized, Open Label Study

This is a Phase IV Randomized, double arm Open labelled trial, conducted at SIMS hospital, Vadapalani, Chennai. It involves all women seeking fertility treatment with poor ovarian reserve, who are planned to undergo assisted conception cycles, including IUI &amp; IVF. The study included women aged between 21 and 45 years, with Poor ovarian reserve with regular menstrual cycles (21–35 days), prestimulation parameters (AFC&lt;5, AMH&lt;1.2 ng/ml), History of previous poor ovarian response &lt;/= 5 oocytes with a conventional stimulation protocol, Couples undergoing the ICSI cycle with ejaculated sperm. The data collected was subjected to statistical testing. The groups were compared in terms of their demographic features and both the groups was found to be equally distributed. Trans-Resveratrol shows that this drug has no advantage over Resveratrol, therapeutically or statistically advantage.

Study protocol on effectiveness of yoga practice on composite biomarker age predictors (yBioAge) in an elderly Indian cohort- two-armed open label randomized controlled trial

IntroductionThe recent development of robust indices to quantify biological aging, along with the dynamic epidemiological transitions of population aging generate the unmet need to examine the extent up to which potential interventions can delay, halt or temporarily modulate aging trajectories.Methods and analysisThe study is a two-armed, open label randomised controlled trial. We aim to recruit 166 subjects, aged 60–75 years from the residential communities and old age clubs in Bangalore city, India, who will undergo randomisation into intervention or control arms (1:1). Intervention will include yoga sessions tailored for the older adults, 1 h per day for 5 days a week, spread for 12 months. Data would be collected at the baseline, 26th week and 52nd week. The primary outcome of the study is estimation in biological age with yoga practice. The secondary outcomes will include cardinal mechanistic indicators of aging- telomere length, interleukin-6 (IL-6), tumor necrosis factor receptor II (TNF-RII), high sensitivity c-reactive protein (hsCRP)], insulin signaling [insulin and IGF1], renal function [cystatin], senescence [growth differentiating factor 15 (GDF-15)] and cardiovascular function [N-terminal B-type natriuretic peptides (NT-proBNP)]. Analyses will be by intention-to-treat model.Ethics & disseminationThe study is approved by the Institutional Ethics Committee of Swami Vivekananda Yoga Anusandhana Samsthana University, Bangalore (ID:RES/IEC-SVYASA/242/2022). Written informed consent will be obtained from each participant prior to inclusion.Trial registration numberCTRI/2022/07/044442.

A study on the effect of Anti- VEGF on retinal venous occlusive disease with macular edema in a tertiary health care centre of southern Assam

Macular oedema is considered to be the primary reason for significant visual loss and impaired visual recovery in patients with retinal venous occlusion and rise in VEGF is strongly implicated in macular edema and as such there is a good rationale in treating these conditions with intravitreal anti-vascular endothelial growth factors. Aim of this study was to assess the effect of anti-VEGF (Bevacizumab) on retinal venous occlusive disease with macular edema.This was prospective open label hospital based interventional study done from June 2021 to May 2022 in fifty eyes of fifty patients diagnosed with macular edema secondary to retinal venous occlusion and Snellen’s visual acuity at presentation of less than 6/12 were included in accordance with the inclusion and exclusion criteria.The results shows statistically significant improvement in mean central macular thickness and mean Snellen’s visual acuity at the end of 12 months and factors like Hypertension, Diabetes mellitus, Dyslipidemia and smoking are found to be highly associated with retinal venous occlusive diseases. The intravitreal anti-VEGF (Bevacizumab) has been found to be effective in improving the macular edema and visual acuity in the study population with retinal venous occlusive diseases to a statistically significant level and that it was more pronounced in cases of BRVO, at the completion of the study period.

Becker Muscular Dystrophy: Could Altering the Natural History of Decline Help Tackle Unmet Medical Need?

This symposium was held as part of the 28th International Annual Congress of the World Muscle Society (WMS), held in Charleston, South Carolina, USA. Speakers reviewed the natural history of Becker muscular dystrophy (Becker), outlined the top line, 12-month data from the ARCH open label study of investigational agent EDG-5506, and aimed to put those results into clinical context. Becker is a serious rare disease with significant physical, emotional, financial, and social impact on the affected individuals and their caregivers. Once function begins to decline, males affected by the progressive X-linked genetic disorder continue to irreversibly lose muscle, ultimately leading to the loss of ambulatory and cardiopulmonary function. After discussing the aetiology of the condition, Erik Niks, Paediatric and Adult Neurologist, Leiden University Medical Center (LUMC), the Netherlands, presented the findings of natural history studies. They showed that while the age at which decline begins varies, once it does start, patients tend to experience a consistent decline in function equivalent to around 1.2–1.3 North Star Ambulatory Assessment (NSAA) points each year. This finding, combined with data on using MRI as a biomarker of disease progression, provides an evidence-based framework for clinical trial design, he argued. Sam Collins, Vice President of clinical development, Edgewise Therapeutics, Boulder, Colorado, USA, then presented topline 12-month data from the ARCH study. It found that EDG-5506 was well tolerated, and, importantly, recorded the stabilisation of functional assessments, including the NSAA, with a trend towards improvement, as well as rapid, sustained, and significant decreases in biomarkers of progression, including those related to muscle damage. Putting the ARCH study data into context, Barry Byrne, Director of the Health Center for Advanced Therapeutics and Powell Gene Therapy Center, University of Florida (UF), Gainesville, USA, explained exactly how declining NSAA status translated into life-altering function loss. Stabilising function, or even reducing the speed of decline, was an important goal for patients, he said, adding that meeting it could help to address significant unmet medical need.

Effectiveness of an amino acid beverage formulation in diarrhea-predominant irritable bowel syndrome: A pragmatic real-world study.

Amino-acid based medical foods have shown promise in alleviating symptoms of drug induced gastrointestinal side effects; particularly, diarrhea-predominant symptoms. Irritable bowel syndrome (IBS) is a gastrointestinal disorder that affects up to 9% of people globally, with diarrhea predominant IBS (IBS-D) being the most prevalent subtype. Further trials are needed to explore potential added benefits when integrated into standard care for IBS-D. To assess the effectiveness of an amino acid-based medical food as an adjunct to standard of care for adults with IBS-D. This is a pragmatic, real world, open label, single arm study comparing a 2-week baseline assessment to a 2-week intervention period. One hundred adults, aged 18 to 65 years, with IBS-D, according to Rome IV criteria, were enrolled after completing a 2-week baseline assessment period and received a 2-week supply of an amino acid based medical food which was consumed at home twice daily on top of their standard of care. The primary outcome was an assessment of tolerability after 2-weeks of consumption, while secondary outcomes included changes in stool consistency (Bristol Stool Form Scale), severity of abdominal pain & discomfort, symptoms of urgency, Global Improvement Survey (GIS), and the IBS severity scoring system (IBS-SSS). The test product was well-tolerated as each participant successfully completed the full 14-day trial, and there were no instances of dropouts or discontinuation of the study product reported. Forty percent of participants achieved a 50% or more reduction in the number of days with type 6-7 bowel movements (IBS-D stool consistency responders). Fifty-three percent of participants achieved a clinically meaningful reduction of 30% in mean weekly pain scores, and 55% experienced the same for mean weekly discomfort scores (IBS-D pain and discomfort responders). Participants experienced a mean -109.4 (95% confidence interval: -130.1, -88.8) point reduction on the IBS-SSS and 52% experienced a minimally clinically important difference of > 95 points. An IBS-SSS category shift from severe to moderate or mild occurred in 69% of participants. For functional symptoms, 76% of participants reported symptom relief on the GIS. The amino acid-based medical food was well-tolerated, when added to the standard of care, and demonstrated improvements in both overall IBS symptom severity and IBS-D symptoms within just 2 wk.

Atezolizumab monotherapy versus chemotherapy in untreated locally advanced or metastatic urothelial carcinoma (IMvigor130): final overall survival analysis from a randomised, controlled, phase 3 study

The primary analysis of IMvigor130 showed a significant progression-free survival benefit with first-line atezolizumab plus platinum-based chemotherapy (group A) versus placebo plus platinum-based chemotherapy (group C) in patients with locally advanced or metastatic urothelial cancer. However, this finding did not translate into significant overall survival benefit for group A versus group C at the final analysis, precluding formal statistical testing of outcomes with atezolizumab monotherapy (group B) versus group C. Here we report the final overall survival results for group B versus group C; this report is descriptive and should be considered exploratory due to the study's statistical design. In this global, partially blinded, randomised, controlled, phase 3 study, patients (aged ≥18 years) who had locally advanced or metastatic urothelial cancer previously untreated in the metastatic setting and Eastern Cooperative Oncology Group performance status of 0-2 were enrolled at 221 hospitals and oncology centres in 35 countries. Patients were randomly assigned (1:1:1), using a permuted block method (block size of six) and an interactive voice and web response system, stratified by PD-L1 status, Bajorin score, and investigator's choice of platinum-based chemotherapy, to receive either atezolizumab plus platinum-based chemotherapy (group A), atezolizumab alone (group B), or placebo plus platinum-based chemotherapy (group C). Sponsors, investigators, and patients were masked to assignment to atezolizumab or placebo in group A and group C; atezolizumab monotherapy in group B was open label. For groups B and C, atezolizumab (1200 mg) or placebo was administered intravenously every 3 weeks. Chemotherapy involved 21-day cycles of gemcitabine (1000 mg/m2 body surface area on day 1 and day 8 of each cycle) plus the investigator's choice of carboplatin (area under the curve 4·5 mg/mL per min or 5 mg/mL per min) or cisplatin (70 mg/m2 body surface area), administered intravenously. Co-primary endpoints were progression-free survival and overall survival in group A versus group C, and overall survival in group B versus group C, tested hierarchically, in the intention-to-treat (ITT) population, and then the populations with high PD-L1 tumour expression (immune cell [IC] expression score of IC2/3) if the results from group A versus group C were significant. Here, we report the co-primary endpoint of overall survival for group B versus group C in the ITT and IC2/3 populations. The ITT population for this analysis comprised concurrently enrolled patients in groups B and C who were randomly assigned to treatment. For the safety analysis, all patients enrolled in group B and group C who received any study treatment were included. The trial is registered with ClinicalTrials.gov, NCT02807636, and is active but no longer recruiting. Between July 15, 2016, and July 20, 2018, 1213 patients were enrolled and randomly assigned to treatment, of whom 362 patients were assigned to group B and 400 to group C, of whom 360 and 359, respectively, were enrolled concurrently (ITT population). 543 (76%) of 719 patients were male, 176 (24%) were female, and 534 (74%) were White. As of data cutoff (Aug 31, 2022), after a median follow-up of 13·4 months (IQR 6·2-30·8), median overall survival was 15·2 months (95% CI 13·1-17·7; 271 deaths) in group B and 13·3 months (11·9-15·6; 275 deaths) in group C (stratified hazard ratio 0·98 [95% CI 0·82-1·16]). The most common grade 3-4 treatment-related adverse events were anaemia (two [1%] in patients who received atezolizumab monotherapy vs 133 [34%] in those who received placebo plus chemotherapy), neutropenia (one [<1%] vs 115 [30%]), decreased neutrophil count (0 vs 95 [24%]), and decreased platelet count (one [<1%] vs 92 [24%]). Serious adverse events occurred in 163 (46%) patients versus 196 (50%). Treatment-related deaths occurred in three (1%; n=1 each, pneumonia, interstitial lung disease, large intestinal obstruction) patients who received atezolizumab monotherapy and four (1%; n=1 each, diarrhoea, febrile neutropenia, unexplained death, toxic hepatitis) who received placebo plus chemotherapy. The final analysis from IMvigor130 did not show a significant improvement in overall survival with first-line atezolizumab monotherapy compared with platinum-based chemotherapy in the intention-to-treat population. The safety profile of atezolizumab monotherapy remained acceptable after extended follow-up, with no new safety signals. F Hoffmann-La Roche.

Effect of a 2-week interruption in methotrexate treatment on COVID-19 vaccine response in people with immune-mediated inflammatory diseases (VROOM study): a randomised, open label, superiority trial

Methotrexate is the first-line treatment for immune-mediated inflammatory diseases and reduces vaccine-induced immunity. We evaluated if a 2-week interruption of methotrexate treatment immediately after COVID-19 booster vaccination improved antibody response against the S1 receptor binding domain (S1-RBD) of the SARS-CoV-2 spike protein and live SARS-CoV-2 neutralisation compared with uninterrupted treatment in patients with immune-mediated inflammatory diseases. We did a multicentre, open-label, parallel-group, randomised, superiority trial in secondary-care rheumatology and dermatology clinics in 26 hospitals in the UK. Adults (aged ≥18 years) with immune-mediated inflammatory diseases taking methotrexate (≤25 mg per week) for at least 3 months, who had received two primary vaccine doses from the UK COVID-19 vaccination programme were eligible. Participants were randomly assigned (1:1) using a centralised validated computer program, to temporarily suspend methotrexate treatment for 2 weeks immediately after COVID-19 booster vaccination or continue treatment as usual. The primary outcome was S1-RBD antibody titres 4 weeks after COVID-19 booster vaccination and was assessed masked to group assignment. All randomly assigned patients were included in primary and safety analyses. This trial is registered with ISRCTN, ISRCTN11442263; following a pre-planned interim analysis, recruitment was stopped early. Between Sept 30, 2021, and March 7, 2022, we screened 685 individuals, of whom 383 were randomly assigned: to either suspend methotrexate (n=191; mean age 58·8 years [SD 12·5], 118 [62%] women and 73 [38%] men) or to continue methotrexate (n=192; mean age 59·3 years [11·9], 117 [61%] women and 75 [39%] men). At 4 weeks, the geometric mean S1-RBD antibody titre was 25 413 U/mL (95% CI 22 227-29 056) in the suspend methotrexate group and 12 326 U/mL (10 538-14 418) in the continue methotrexate group with a geometric mean ratio (GMR) of 2·08 (95% CI 1·59-2·70; p<0·0001). No intervention-related serious adverse events occurred. 2-week interruption of methotrexate treatment in people with immune-mediated inflammatory diseases enhanced antibody responses after COVID-19 booster vaccination that were sustained at 12 weeks and 26 weeks. There was a temporary increase in inflammatory disease flares, mostly self-managed. The choice to suspend methotrexate should be individualised based on disease status and vulnerability to severe outcomes from COVID-19. National Institute for Health and Care Research.