Subjects In Arm Research Articles

Trompe-la-mort

BackgroundUncertainty is consubstantial with psychoanalytic practice, which is based on an openness to the unknown. The fundamental rule institutes the experience on which the treatment is based, and is, at the same time, the most appropriate methodological answer to the logics of infantile sexuality and the motor of its subjective appropriation. ObjectivesTo this fertile uncertainty, the author opposes an uncertainty based on vital dependancy that, on account of passionate bonding, tends to freeze the analytic process and threatens to destroy the cure. Therefore, it is a question of problematizing the regime of uncertainty proper to limit-experiences. This experience of “death struggle against death” is engaged when an apparently hopeless hold is exerted on a human being and dispossesses him/her “of an impersonal right to life” (N. Zaltzman, 1998). What resources does psychoanalytic practice have in such a context? MethodThe author draws on both his clinical practice as a psychoanalyst and his work as a supervisor of teams confronted with situations of extreme precarity. Anthropological and artistic fields are also called upon to explore the logic of the limit-experience. The author examines the concept of the anarchist drive theorized by Nathalie Zaltzman: he proposes a critical re-examination while underlining its great value on the clinical level. In the wake of this questioning, the author questions psychoanalysis with regard to the environmental crisis, conceived of a limit-experience to come. ResultsWhat resources does psychoanalysis possess in its struggles with limit-experiences? Clinical work in the anarchist regime secures the constitution of a singular resistance in the heart of the death zones. Its vocation is to psychically arm subjects with a capacity to enjoy existence in spite of everything, without sinking into psychosis, apathy, or alienation. Marked by a limit-experience (the Covid-19 crisis, for example), a psychoanalysis worked-through by the anarchist drive can, in return, undertake the work of re-examining of its foundations and of displacing its founding paradigms. ConclusionThis text questions the clinical and theoretical paradigm shifts required by a specific regime of uncertainty, that of the limit-experience. The clinical questioning is coupled with an anthropological questioning, against the background of the environmental crisis. This text constitutes a first approach and tries to lay down some milestones in the heart of a considerable construction site.

THE ROLE OF HERBAL IMMUNOMODULATORS AS ADJUVANT THERAPY FOR ASYMPTOMATIC AND MILDLY SYMPTOMATIC COVID-19: AN EXPLORATORY CLINICAL STUDY

Objectives: The objective of the study is to evaluate herbal immunomodulators (Septilin and Bresol) as a possible adjuvant therapy for the treatment of asymptomatic and mildly symptomatic COVID-19. Methods: Randomized, open-label, comparative clinical study. Subjects were randomized to either arm I [Septilin and Bresol+standard of care (SOC)] or arm II (SOC). This study was registered on CTRI (CTRI/2020/06/025801). Results: Subjects in arm I showed a greater reduction in levels of interleukin-6 tumor necrosis factor-α following treatment than in arm II. Subjects in arm I showed a greater increase in levels of interferon (IFN)-β and IFN-λ than those in arm II. There was a greater reduction in D-dimer in arm I than in arm II subjects (64.28% vs. 35.59%) and all arm I subjects had D-dimer values in the normal range compared to 70% of arm II subjects. There were statistically significant reduction in lactate dehydrogenase and neutrophil-to-lymphocyte ratio in arm I (p<0.016 and p<0.013, respectively). Clinical assessments during the post-illness convalescence period showed significant improvements in fatigue assessment scores and quality of life. Conclusion: This herbal combination as an adjuvant to SOC may provide additional long-term benefits in COVID-19 infection by reducing inflammation. This treatment may offer a good addendum for the management of post-COVID-19 illness.

Intestinal Absorption of Lipids Using a Pancreatic Enzyme-Free Nutritional Supplement in Patients with Cystic Fibrosis: A Randomized, Double-Blind, Crossover Pilot Trial.

Nutritional supplements for patients with exocrine pancreatic insufficiency (EPI) typically utilize pancreatic enzyme replacement therapy (PERT) which is associated with gastrointestinal side effects. We evaluated serum triglyceride levels in patients with cystic fibrosis following consumption of an enzyme-modified oil oral nutritional supplement (EMO-ONS) versus a standard triacylglycerol-based ONS product (TAG-ONS) used concomitantly with PERT and patient tolerability between the two approaches. Ten subjects with CF and EPI taking PERT were enrolled in a single-center, double-blind, cross-over proof of concept trial. Five subjects randomized to Arm 1 were administered a PERT placebo and EMO-ONS and 5 subjects in Arm 2 were administered TAG-ONS+PERT. After 4 to 14 days, subjects received the opposite ONS. Serum triglyceride levels were measured at baseline and hourly for 6 h. Following the above, subjects were randomly assigned to receive 2 daily servings of EMO-ONS+PERT placebo or TAG-ONS+PERT at home for 7-days, self-reporting gastrointestinal symptoms daily. Mean change in peak serum triglyceride levels were similar for both groups (EMO-ONS = 41.9 ± 46.7 mg/dL vs. TAG-ONS+PERT = 46.4 ± 44.1 mg/L; p = 0.85). There was no difference in mean ratio of the serum triglyceride AUC between the two groups (p = 0.58) or self-reported gastrointestinal tolerance. EMO-based products may provide a PERT-free alternative to traditional ONS products in patients with cystic fibrosis.

A Randomized Double-blind Placebo-controlled Trial of Oral Aspirin for Protection of Melanocytic Nevi Against UV-induced DNA Damage.

DNA damage plays a role in ultraviolet (UV)-induced melanoma. We previously showed that aspirin (ASA) can suppress prostaglandin-E2 (PGE2) and protect melanocytes from UV-induced DNA damage in mice, and suggested that taking ASA before acute sun exposure may reduce melanoma risk. We conducted a prospective randomized placebo-controlled trial to determine if orally administered ASA could suppress PGE2 in plasma and nevi and protect nevi from UV-induced DNA damage. After obtaining plasma and determining the minimal erythemal dose (MED) in 95 subjects at increased risk for melanoma, they were randomized to receive a daily dose of placebo, 81 mg ASA, or 325 mg ASA, in double-blind fashion for one month. After this intervention, one nevus was irradiated (dose = 1 or 2 MED) using a solar simulator. One day later, MED was re-determined, a second plasma sample was obtained, and the UV-irradiated nevus and an unirradiated nevus were removed. ASA metabolites were detected in the second plasma sample in subjects in the ASA arms. There were no significant differences in the pre- and post-intervention MED between those patients receiving ASA and placebo. Significantly reduced PGE2 levels were detected in plasma (second vs. first samples) and in nevi (both unirradiated and UV-treated) in subjects receiving ASA compared to placebo. Comparing UV-treated nevi from the ASA and placebo cohorts, however, did not reveal significant reductions in CD3-cell infiltration or 8-oxoguanine and cyclobutane pyrimidine dimers. Thus ASA did not effectively protect nevi from solar-simulated UV-induced inflammation and DNA damage under the conditions examined. PREVENTION RELEVANCE: Despite promising rationale, ASA at conventional dosing was not able to protect nevi against UV-induced DNA damage under the conditions examined.See related Spotlight, p. 71.

Progression from human papillomavirus (HPV) infection to cervical lesion or clearance in women (18–25 years): Natural history study in the control arm subjects of AS04-HPV-16/18 vaccine efficacy study in China between 2008 and 2016

ABSTRACT Background Cervical cancer is the third most frequent cancer in Chinese women aged 15–44 years old. Human papillomavirus (HPV) is recognized as the main etiologic agent of cervical carcinomas. This study aims to better understand the natural history of HPV infections in Chinese women aged 18–25 years. Research Design and Methods Data from 3,025 control arm women (AS04-HPV-16/18 vaccine trial) were analyzed to assess the probability of progression or clearance from a 6-month persistent infection (6MPI) to a cervical intraepithelial neoplasia grade 2 or greater (CIN2+), and the association with clinical determinants. Data were analyzed using univariate and multivariable Cox models. Results A total of 1,324 women with 3,814 HPV infections were included, and 65.7% of the women had at least one 6MPI. Among those 6MPI, 5.0% progressed to CIN2+, while 61.0% cleared within 6 months. The risk of progression from 6MPI to CIN2+ was substantially higher for oncogenic versus non-oncogenic HPV types. Conclusions Oncogenic HPV infections showed lower clearance and higher risk to progress to CIN2 +. These findings observed in a population of Chinese women, confirmed previous findings from multinational studies. Trial Registration The PATRICIA and AS04-HPV-16/18 vaccine trials are registered at ClinicalTrials.gov (NCT00779766 and NCT00122681).

Effect of mulmina mango as an adjunct to standard of care treatment on COVID-19 positive subjects undergoing treatment for COVID-19 in hospital quarantine (Dedicated Covid Health Centre)

There are no approved drugs to treat COVID-19, and the vaccine is likely to be ready by early 2021. Many clinical studies are ongoing around the globe to find a cure or prevention of the disease. The objective of the proposed study is to determine the efficacy and safety profile of Mulmina Mango as an adjunct to standard of care treatment on COVID-19 positive subjects undergoing treatment for COVID-19 in Hospital Quarantine. Settings and Design: The enrolled subjects were randomized into either of the two treatment arms in the ratio of 1:1. The freshly diagnosed (24-48 hrs.) COVID-19 positive Male or Female is aged 20 to 65 years (both inclusive) hospitalized patients were approached and checked for their eligibility. They were recruited after signing the written informed consent form. The number of patients included in the study is 48. In efficacy, both the treatment arms and the reduction in clinical symptom scale value and ordinal scale value are seen on day 7. On the ordinal scale, 41.7% of subjects in Treatment arm A showed a reduction of 2 points on the day, and 16.7% of subjects show 2 points reduction in Treatment arm B. In Safety results, there was no clinically significant finding in safety parameters in Treatment arm B. Mulmina Mango showed encouraging results concerning RTPCR, CRP, Dopamine, IgG, CD4, and CD8 parameters. The properties of Mulmina Mango are highlighted below, along with the parameters for each property. Mulmina Mango, COVID-19, Treatment Arm A, Treatment Arm B, MoHFW (Ministry of Health and Family Welfare)

Matching design for augmenting the control arm of a randomized controlled trial using real-world data

ABSTRACT Randomized clinical trials (RCTs) have often been considered as the gold standard in drug development, but they may not be fully powered due to limited patient population and can even lead to ethical concerns in rare disease studies. In situations like this, real-world data (RWD)/historical data can be utilized to augment or possibly serve as the control arm for the current trial. If a subset of subjects from the RWD/historical trial could be matched to the concurrent control arm subjects and they are deemed comparable following certain criteria, then pooling the matched subjects from the historical control arm and the concurrent control arm can boost the power. In this paper, we propose two matching methods of borrowing historical control data that not only balance key observed baseline covariates but also ensure the comparability of responses between the historical and concurrent controls. Close similarity in response variables among controls reduces Type I error inflation and provides further protection against unmeasured confounding bias, which is a major challenge in using RWD. Simulation studies are conducted to evaluate the empirical performance of the two matching methods in terms of Type I error rate and power, and an illustrative description of a planned study is presented.

Single-dose versus multiple-dose antibiotics prophylaxis for preventing caesarean section postpartum infections: A randomized controlled trial.

Background:Caesarean section, a common obstetric surgical procedure, is a major predisposing factor for puerperal infections, requiring the need for antibiotic prophylaxis. Evidence suggests that single-dose antibiotic prophylaxis has comparable efficacy to multiple-dose antibiotic prophylaxis, but with a lower cost and risk of antibiotic resistance. However, single-dose antibiotic prophylaxis after caesarean section is not generally used in many centres in sub-Saharan Africa.Objective:This study aimed to compare the effectiveness of single- versus multiple-dose antibiotic prophylaxis to prevent post-caesarean section infections.Methodology:This open-label, randomized controlled trial involved 162 consenting patients admitted for caesarean section (elective or emergency) at the Federal Medical Centre Keffi. They were distributed randomly into treatment arm A or B. Subjects in both arms received intravenous ceftriaxone (1 g) and metronidazole (500 mg) 30–60 min before incision; subjects in arm B received additional parenteral doses for 48 h and then cefuroxime 500 mg tablets every 12 h and metronidazole 400 mg tablets every 8 h for 5 days. The patients were monitored for 2 weeks for evidence of wound infection, febrile morbidity and clinical endometritis.Result:There was no statistical difference in the incidence of wound infection (6.6% versus 7.4%; p = .882) and febrile morbidity (11.8% versus 11.1%, p = .807). However, clinical endometritis (0.0% versus 6.1%, p = .028) was statistically significant with none reported in the single-dose arm.Conclusion:Single-dose ceftriaxone and metronidazole is as effective as multiple doses for antibiotic prophylaxis to prevent post-caesarean section infections. Adoption of this approach in low-risk patients would reduce the cost of prophylactic antibiotics, workload for staff and antibiotic resistance.

Evaluation of the Immunomodulatory Effects of C-Vx on the Innate and Adaptive"Immune" System:Preliminary Results

Objectives: In this preliminary study, the in vitro effect of C-Vx in human PBMCs and the in vivo effect of C-Vx in rats were investigated. Methods: The human part was analyzed in PBMCs isolated from healthy subjects. Apoptotic index, cytotoxic activity of CD8+ T and NK cells, and cell proliferation of CD3+, CD4+, CD8+ T and NK cells in response to different doses of C-Vx were investigated. Also the hematological and biochemical parameters of the rats administered subcutaneously in three different doses of C-Vx were monitored for 14-days. Results: Increased CD107a expression in response to C-Vx on NK cells but not on CD8+ T cells support the increasing of NK cell cytotoxicity. C-Vx alone was capable of triggering proliferation of T and NK cells. The PHA-induced proliferation of CD3+ and CD4+ T cells was diminished in response to C-Vx, while PHA-induced CD8+ T cell proliferation was up-regulated. PHA-triggered proliferation of total NK cells was enhanced with the existence of C-Vx. C-Vx was well tolerated in rats with no serious adverse effects or mortality (death) after 14-days of follow-up. Biochemical-parameters (creatinine, blood urea nitrogen, etc.) were not significantly different among treated and control groups. The levels of white blood cells and lymphocytes were increased up to two-folds in the C-Vx group (especially 0.25 ml/day) as compared to the control group. Conclusion: Taken together, these preliminary findings support the immunomodulatory effects of C-Vx. But these findings should cautiously be evaluated due to the low numbers of subjects in both human and experimental arms.

Genicular Artery Embolization: Beyond the Placebo Effect, and Planning for the Long Road Ahead

Genicular artery embolization (GAE) has emerged in the field of interventional radiology as a treatment for knee pain related to osteoarthritis. This novel treatment is based on the hypothesis by Okuno et al and supported by multiple small single-arm studies ( 1 Okuno Y. Korchi A.M. Shinjo T. et al. Transcatheter arterial embolization as a treatment for medial knee pain in patients with mild to moderate osteoarthritis. Cardiovasc Intervent Radiol. 2015; 38: 336-343 Crossref PubMed Scopus (50) Google Scholar , 2 Okuno Y. Korchi A.M. Shinjo T. et al. Midterm clinical cutcomes and MR imaging changes after transcatheter arterial Embolization as a treatment for mild to moderate radiographic knee osteoarthritis resistant to conservative treatment. J Vasc Interv Radiol. 2017; 28: 995-1002 Abstract Full Text Full Text PDF PubMed Scopus (59) Google Scholar , 3 Lee S.H. Hwang J.H. Kim D.H. et al. Clinical outcomes of transcatheter arterial embolisation for chronic knee pain: mild-to-moderate versus severe knee osteoarthritis. Cardiovasc Intervent Radiol. 2019; 42: 1530-1536 Crossref PubMed Scopus (40) Google Scholar , 4 Landers S. Hely R. Page R. et al. Genicular artery embolization to improve pain and function in early-stage knee osteoarthritis-24-month pilot study results. J Vasc Interv Radiol. 2020; 31: 1453-1458 Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar , 5 Bagla S. Piechowiak R. Hartman T. et al. Genicular artery embolization for the treatment of knee pain secondary to osteoarthritis. J Vasc Interv Radiol. 2020; 31: 1096-1102 Abstract Full Text Full Text PDF PubMed Scopus (44) Google Scholar , 6 Little M.W. Gibson M. Briggs J. et al. Genicular artEry embolizatioN in patiEnts with oSteoarthrItiS of the knee (GENESIS) using permanent microspheres: interim analysis. Cardiovasc Intervent Radiol. 2021; 44: 931-940 Crossref PubMed Scopus (26) Google Scholar ) that pain is in part due to hypervascularity and inflammation, but several considerations need to be addressed. These include GAE's indications, mode of action, mechanism of clinical success achieved by short-term embolization using imipenem/cilastatin crystals vs other embolics, and the possibility of symptom improvement due to the placebo effect. In particular, concern about the placebo effect is plausible given that embolization using imipenem/cilastatin crystals, which are smaller and more rapidly soluble than typical embolic materials ( 7 Yamada K. Jahangiri Y. Li J. et al. Embolic characteristics of imipenem-cilastatin particles in vitro and in vivo: implications for transarterial embolization in joint arthropathies. J Vasc Interv Radiol. 2021; 32: 1031-1039.e2 Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar ), have yielded outcomes similar to those of permanent embolic materials ( 2 Okuno Y. Korchi A.M. Shinjo T. et al. Midterm clinical cutcomes and MR imaging changes after transcatheter arterial Embolization as a treatment for mild to moderate radiographic knee osteoarthritis resistant to conservative treatment. J Vasc Interv Radiol. 2017; 28: 995-1002 Abstract Full Text Full Text PDF PubMed Scopus (59) Google Scholar ). Osteoarthritic pain response is also highly susceptible to the placebo effect ( 8 Doherty M. Dieppe P. The “placebo” response in osteoarthritis and its implications for clinical practice. Osteoarthritis Cartilage. 2009; 17: 1255-1262 Abstract Full Text Full Text PDF PubMed Scopus (89) Google Scholar ). Therefore, a sham-controlled study is extremely valuable to assess the efficacy of GAE. However, it is difficult to justify a sham-controlled study in the field of interventional radiology because subjects in the control arm would be at risk of adverse events that may not be trivial, such as infection or bleeding after arterial access.

Piloting a randomized, double-blind, placebo-controlled study design at a community hospital to evaluate prophylactic antibiotics in endoscopic carpal tunnel release: Clinical, logistic, and economic considerations

Surgical site infection is low following endoscopic carpal tunnel release (ECTR), yet antibiotic prophylaxis is still common in these procedures. This study piloted a randomized, double-blind, placebo-controlled study design at a community hospital to generate discourse in support of discontinuing antibiotic prophylaxis in ECTR procedures. Patients undergoing dual-incision endoscopic carpal tunnel release at a single community hospital between May 1, 2018 and December 31, 2020 were enrolled in a pilot study. Subjects were randomized to prophylactic antibiotics or placebo saline solution arms. Infection rates and complications were compared. Study workflow processes were streamlined to facilitate eventual study duplication at additional sites. One hundred twenty-four subjects (140 hands) were included in the final analysis. No subjects in either study arm sustained an infection. The race and ethnic distributions of the study sample closely resembled those of the census-reported community distributions. Implementing a randomized, double-blind, placebo-controlled study at a community hospital presented numerous challenges. Although statistical nor clinical significance could be established in the absence of infection, these results validate what is presently known regarding the low likelihood of infection in clean hand surgery and demonstrated the feasibility of designing and implementing methodologically sound research in a community setting. Duplicating this study design at additional research sites can provide the level of evidence necessary to discourage unnecessary prophylactic antibiotic administration in clean hand surgery. • Surgical site infection following endoscopic carpal tunnel release is very low. • Prophylactic antibiotics may not be necessary in carpal tunnel procedures. • A randomized-controlled trial was successfully piloted at a community hospital. • This study design can be duplicated at more sites to obtain higher power.

Oral intake of a new full-spectrum hyaluronan improves skin profilometry and ageing: a randomized, double-blind, placebo-controlled clinical trial.

Skin aging is a physiological condition which leads to structural and functional changes in skin. Common signs of aging are the gradual decrease of hyaluronic acid (HA) in the skin and the appearance of wrinkles. Therefore, effective HA supplementation could counteract HA deficiency and improve skin parameters, providing a safe profile for use which is easily incorporated into daily routine. To evaluate a food supplement containing a wide range of hyaluronans of different molecular weights (full-spectrum hyaluronan [FS-HA]) in order to ameliorate skin conditions in adult females. Sixty subjects showing mild-to-moderate skin aging signs were enrolled in a double-blind, randomized, placebo-controlled clinical trial to receive 200mg/day of FS-HA (ExceptionHYAL® Star), or placebo, for 28 days. Dermatological parameters were evaluated at T0d and T28d. Product efficacy and tolerance were further evaluated using a self-assessment questionnaire. In addition, HA serum levels were weekly evaluated in a proportion of enrolled subjects. After only 28 days, subjects in the active arm showed a statistically significant improvement in all evaluated dermatological parameters related to skin aging. Skin became more hydrated (+10.6%) and protected from dehydration, with a decrease in both wrinkle depth (-18.8%) and volume (-17.6%) and increase in elasticity and firmness (+5.1%). Instrumental results were further confirmed by self-assessment questionnaire outcomes. Administration of a food supplement based on innovative hyaluronans from bio-fermentation, characterized by a wide range of molecular weights, resulted in a quick and significant amelioration of typical signs of skin aging.

Shining new light on dementia treatment: ADAS‐Cog and quantitative EEG evidence of cognitive improvement in early and mid‐stage dementia using self‐administered 1070 nm transcranial near‐infrared photobiomodulation

AbstractBackgroundThe current evidence supporting nonpharmacologic treatment of dementia has focused mainly on environmental or interactive interventions, e.g., music, sensory stimulation, simulated presence, and validation therapies. Exercise and light therapy improved/maintained activities of daily living, while cognitive stimulation, exercise and reminiscence improved cognition. The strongest evidence for reducing emotional disorders so far has employed music, psychological interventions and reminiscence. PubMed lists 918 citations related to non‐pharmacological treatments for dementia with music therapy and behavioral management techniques being the most efficacious showing modest improvements at best. Non‐pharmacologic treatment interventions directed at reversing both cognitive and behavioral symptom of dementia are small, few in number and with wide variation in defining outcome measures, and little comparative data across approaches to guide further research efforts or systematic clinical applicability. Photobiomodulation using brief, daily, pulsed LED‐driven transcranial infrared light stimulation, has been shown to markedly alter both cognitive and behavioral symptoms in people with mild to moderate dementia. Improved functioning has been documented by both standard neuropsychological testing and noninvasive Quantitative electroencephalographic (QEEG) measures of functional connectivity. This presentation describes a multi‐site, randomized, placebo controlled, at‐home, self‐administered treatment protocol employing pulsed transcranial and intraocular 1068nm near‐infrared light to achieve reversal of cognitive decline, and improve dementia patient’s physical and interpersonal behavior. Study subjects (n=100) were evaluated at two locations at baseline, midpoint (30 days) and termination (60 days) using both Quantitative EEG and ADAS‐Cog and caregiver evaluation of subject’s change in ADLs. This trial was a replication of an earlier pilot trial and a recent safety/feasibility trial with no adverse events reported in any study. MMSE improved 21.0%, 4.8 points in the active treatment group and 1.6 points in the placebo group. Sleep duration increased in the active treatment group by an hour after 8 days of treatment and caregivers noted improved mood, energy, and positive engagement in daily activities. None of these functional changes were noted in the placebo arm subjects. Active group’s clock drawing improved 20% and no change in the control group. Logical memory recall improved 3.3 points (p< .03) and time to completion of Trails A&B decreased 23.7% (p<.03).

Incidental Findings on Low-Dose CT Scan Lung Cancer Screenings and Deaths From Respiratory Diseases

Incidental respiratory disease-related findings are frequently observed on low-dose CT (LDCT) lung cancer screenings. This study analyzed data from the National Lung Screening Trial (NLST) to assess the relationship between such findings and respiratory disease mortality (RDM), excluding lung cancer. Are incidental respiratory findings on LDCT scanning associated with increased RDM? Subjects in the NLST LDCT arm received three annual screens. Trial radiologists noted findings related to possible lung cancer, as well as respiratory-related incidental findings. Demographic characteristics, smoking history, and medical history were captured in a baseline questionnaire. Kaplan-Meier curves were used to assess cumulative RDM.Multivariate proportional hazards models were used to assess risk factors for RDM; in addition to incidental CT scan findings, variables included respiratory disease history (COPD/emphysema, and asthma), smoking history, and demographic factors (age, race, sex, and BMI). Of 26,722 subjects in the NLST LDCT arm, 25,002 received the baseline screen and a subsequent LDCT screen. Overall, 59%were male, 26.5%were aged≥ 65 years at baseline, and 10.6%reported a history of COPD/emphysema. Emphysema on LDCT scanning was reported in 30.7%of subjects at baseline and in 44.2%at any screen. Of those with emphysema on baseline LDCT scanning, 18%reported a history of COPD/emphysema. Median mortality follow-up was 10.3 years. There were 3,639 deaths, and 708 were from respiratory diseases. Among subjects with no history of COPD/emphysema, 10-year cumulative RDM ranged from 3.9% for subjects with emphysema and reticular opacities to 1.1% for those with neither condition; the corresponding range among subjects with a COPD/emphysema history was 17.3% (both) to 3.7% (neither). Emphysema on LDCT imaging was associated with a significantly elevated RDM hazard ratio (2.27; 95%CI, 1.92-2.7) in the multivariate model. Reticular opacities (including honeycombing/fibrosis/scar) also had a significantly elevated hazard ratio (1.39; 95%CI, 1.19-1.62). Incidental respiratory disease-related findings observed on NLST LDCT screens were frequent and associated with increased mortality from respiratory diseases.

CTIM-28. MDNA55, AN INTERLEUKIN-4 RECEPTOR TARGETED IMMUNOTHERAPY, FOR RECURRENT GBM DELIVERED BY CONVECTION ENHANCED DELIVERY (CED)

Abstract BACKGROUND MDNA55 is an IL4R-targeted toxin in development for treatment of recurrent glioblastoma (rGBM). MDNA55 binds to IL4R expressed by tumor cells and non-malignant cells of the tumor microenvironment. METHOD MDNA55-05 was an open-label, single-arm study of MDNA55 delivered by CED as a single treatment in patients with 1st or 2nd recurrence following de novo GBM, IDH wild type status and not indicated for resection at relapse. Dose volumes (up to 60mL) and concentration of MDNA55 (1.5 to 9.0 μg/mL) were studied. RESULTS MDNA55 showed an acceptable safety profile at all doses tested. Median OS (mOS) amongst all subjects was 11.9 months, OS-24 was 20%, and PFS-12 was 27%. Among subjects expressing high levels of IL4R (irrespective of MDNA55 dose) and low levels of IL4R expression administered high dose (≥ 180μg) of MDNA55 (IL4Rhi + IL4Rlo/hd), mOS further improved to 14.0 months with OS-24 of 20%. Unmethylated MGMT promoter status did not affect MDNA55 treatment outcomes. In the IL4Rhi + IL4Rlo/hd population (N=17), mOS was 14.9 months with OS-24 of 22%. Following treatment with high concentrations of MDNA55 (6.0 or 9.0 μg/mL), transient (median of 3 cycles) low dose Avastin (5mg/kg q2w or 7.5mg/kg q3w) was used for symptom control and steroid sparring. Among these subjects, mOS amongst all comers (N=9) and the IL4Rhi + IL4Rlo/hd group (N=8) increased to 21.8 and 18.6 months with OS-24 of 44% and 38%, respectively. CONCLUSIONS MDNA55 shows potential to benefit all rGBM patients treated at high dose irrespective of IL4R expression. In the 1:1 randomized Phase 3 trial, the study will enrol two-thirds of subjects in the SOC arm from a matched external control arm. Unlike conventional RCTs, the hybrid design sets a new precedent for GBM trials, allowing robust OS analysis while significantly reducing the number of subjects randomized to SOC arm.

Health-Related Quality of Life in a Biologic Assignment Trial of Reduced Intensity Hematopoietic Cell Transplantation Based on Donor Availability in Patients Aged 50-75 with Advanced Myelodysplastic Syndrome

Health-Related Quality of Life in a Biologic Assignment Trial of Reduced Intensity Hematopoietic Cell Transplantation Based on Donor Availability in Patients Aged 50-75 with Advanced Myelodysplastic Syndrome

A randomised, controlled trial of meditation and yoga in permanent atrial fibrillation: the MAYA study

Abstract Background The role of yoga in paroxysmal atrial fibrillation (AF) is known. But its role in permanent AF has not been studied. Purpose The objectives of our study are to evaluate the effects of yoga on symptoms, heart rate, quality of life, hospitalisations, medication adherence and echocardiographic parameters in permanent AF. Methods We conducted a single centre, randomised, participant blinded, parallel group, sham-controlled study between October 2019 and September 2020. We included patients aged 18–65 years with permanent AF due to any cause. Patients in New York Heart Association (NYHA) class≥3, modified European Heart Rhythm Association (mEHRA) class ≥3 and left ventricular ejection fraction (LVEF)<30% were excluded. Total of 84 patients underwent randomisation into two groups of 42 each. None of the participants had prior knowledge or contraindications to yoga. Subjects in yoga arm underwent supervised and self-performed yoga sessions consisting of various asanas, pranayamas and dhyana, while those in the sham arm underwent supervised and self-performed joint exercises, each session lasting for 60 minutes/day for 6 days a week along with guideline directed medical therapy in both arms. The primary endpoints were improvement in NYHA class, mEHRA class, heart rate at rest and after 6 minute walk test, 6 minute walk distance, quality of life, medication adherence, hospitalisations, LVEF and left atrial volume index at 3 months. The secondary endpoints included the same parameters assessed at 1month. Quality of life was assessed by the short form (SF)-36 questionnaire which has eight domains. Scores for each domain range from 0 to 100, with a higher score defining a more favourable health state. All analyses were based on intention to treat principle. Results The groups were well-matched at baseline. The mean age of study participants was 50.62±12.97 years, 56% were women and the most common risk factor was rheumatic heart disease found in 47.6% of the cases. Four patients in the yoga group and 3 in the sham group were lost to follow up. There was significant improvement in various parameters in the yoga arm at 1 and 3 months. (Figures 1 and 2). Hospitalisation at 3 months was lower in the yoga arm (0.73±0.81) versus sham arm (1.13±0.93); p=0.044. Out of 38 patients in the yoga arm, 6 patients had improvement in the medication adherence compared to 9 patients (out of 39) in the sham arm at 3 months, p=0.419, OR (95% CI) = 0.62 (0.19–1.96). Higher the compliance to yoga, defined by the number of sessions per week, more was the improvement in various parameters. No harms were noted. Conclusion Among patients of permanent AF already on medical therapy, yoga significantly improves symptoms, heart rate, functional capacity, quality of life and hospitalisations when compared to a sham procedure. Larger, multicentre, double blinded studies are required to generalise the results, though participant blinding cannot be 100% assured. Funding Acknowledgement Type of funding sources: None.

Comparative evaluation of anesthetic efficacy of inferior alveolar nerve block and inferior alveolar nerve block plus buccal or lingual infiltration using articaine in mandibular molars with irreversible pulpitis: a preliminary prospective randomized single-blind clinical trial.

This study was designed as a prospective randomized single-blind clinical trial to compare the anesthetic efficacy of inferior alveolar nerve block (IANB), IANB plus buccal infiltration, and IANB plus lingual infiltration of 4% articaine with 1:100,000 epinephrine in mandibular molars with irreversible pulpitis. Sixty healthy volunteers who had a first or second mandibular molar diagnosed with irreversible pulpitis participated in the present study. This study was composed of three arms for the first molar and three arms for the second molar. Subjects in test arm A received two IANB injections (3.6 mL). Subjects in test arm B received 1.8 mL IANB injection plus 1.8 mL buccal infiltration. Subjects in test arm C received 1.8 mL IANB injection plus 1.8 mL lingual infiltration. Articaine (4%) with 1:100,000 epinephrine was used for all injections. The subject's pain during access preparation and pulp extirpation was recorded on the Heft-Parker visual analog scale. Success was defined as "none" or "mild" pain during treatment. Kruskal-Wallis test was used to compare pain categories in three groups of interventions for each mandibular molar. IANB with a supplemented buccal infiltration provided more success than IANB alone or IANB plus lingual infiltration, in first molars (P = .019). There were no significant differences between the three injection techniques in second molars (P = .795). Adding a supplemental buccal infiltration to a standard IANB was more successful in providing pain-free treatment for patients experiencing irreversible pulpitis in mandibular first molars.

Safety and Immunogenicity of a novel three-dose recombinant nanoparticle rabies G protein vaccine administered as simulated post exposure immunization: A randomized, comparator controlled, multicenter, phase III clinical study

ABSTRACT Background Rabies vaccines are lifesaving in human post animal exposure. However, the compliance to the complete course of vaccine is found to be only 60%. Hence, there is a need for safe and immunogenic, shorter course vaccine that can enhance the compliance and effectively prevent the disease. Objectives To establish a noninferiority of a novel three-dose recombinant rabies G protein vaccine to be administered as simulated postexposure prophylaxis when compared to five-dose WHO prequalified vaccine for better safety and immunogenicity. Methods A multi-centric, open label, assessor blind, center-specific block randomized, parallel design, phase III clinical study was conducted among 800 subjects. The eligible subjects were randomized in 2:1 ratio for recombinant rabies G protein vaccine and the reference vaccine. Subjects in recombinant rabies G protein vaccine arm received three doses of vaccine on days 0, 3, and 7, while subjects in reference vaccine arm received five doses of WHO prequalified vaccine on days 0, 3, 7, 14, and 28. Results The socio-demographic characteristics of the two arms were comparable. About 9.9% subjects in recombinant rabies G protein vaccine arm and 17.2% subjects in reference arm reported adverse events. The sero-protection on day 14 was found to be 99.24% and 97.72% in recombinant rabies G protein vaccine arm and reference vaccine arm respectively and the difference was statistically nonsignificant. Conclusion The novel three-dose recombinant rabies G protein vaccine administered as simulated postexposure prophylaxis was noninferior to five dose WHO prequalified vaccine in terms of safety and immunogenicity.

Effect of intravenous sedation on patients’ visual experience and vital signs during cataract surgery under topical anesthesia: A randomized controlled trial

PurposeEffect of intravenous sedation on patients’ visual experience and vital signs during cataract surgery under topical anesthesia: a randomized controlled trial. DesignProspective, double masked, randomized controlled trial. Methods150 eyes of 150 patients undergoing phacoemulsification and IOL implantation under topical anesthesia were randomized to receive either intravenous midazolam (0.015 ​mg/kg) or normal saline. The patients’ experience was evaluated using a questionnaire. Vital signs including blood pressure and heart rate were measured before, during and after surgery. Mean arterial pressure (MAP) was calculated. ResultsBoth groups were comparable except that fewer patients in the control group were pseudophakic in the fellow eye (25.3% vs. 41.3%). More patients in the control group perceived hand movements (p ​< ​0.01), surgeon/medical staff (p ​= ​0.04) and sudden increase in vision during surgery (p ​< ​0.01) compared to midazolam group. More control group patients experienced fear (p ​< ​0.001), pain (p ​= ​0.06) and unpleasant surgical experience (20.3% vs. 1.3%, p ​< ​0.001). They also experienced greater fluctuation in MAP (16.9 ​± ​7.9 vs.7.2 ​± ​5.3, p ​< ​0.001) and this was accentuated in hypertensives. After adjusting for age, gender, hypertension status and other eye lens status, multivariable logistic regression analysis revealed that subjects in the control arm (OR ​= ​11.7, 95% [CI] ​= ​1.3–108, p ​= ​0.03), had a longer duration of surgery, experienced pain and more likely to report unpleasant experience. Adjusting for similar covariates, multivariable linear regression analysis showed that control group patients (β ​= ​8.5 ​mmHg, 95% CI ​= ​6.2–10.8, p ​= ​0.03) had hypertension, experienced fear during surgery and greater fluctuations in the MAP. ConclusionsA sedative dose of intravenous midazolam during phacoemulsification under topical anesthesia significantly reduces patients’ visual experience, fear and fluctuations in MAP and improves overall surgical experience.