scholarly journals TeleNeurological evaluation and Support for the Emergency Department (TeleNS-ED): protocol for an open-label clinical trial

BMJ Open ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. e048293
Author(s):  
Jessica Mandrioli ◽  
Mario Santangelo ◽  
Antonio Luciani ◽  
Stefano Toscani ◽  
Elisabetta Zucchi ◽  
...  
Keyword(s):  
Emergency Department ◽  
Clinical Investigation ◽  
Neurological Diseases ◽  
Medical Personnel ◽  
Primary Objective ◽  
Control Group ◽  
National Guidelines ◽  
Open Label ◽  
Time Saving ◽  
Hospital Networks

IntroductionThe COVID-19 pandemic compelled health systems to protect patients and medical personnel during transit in hospitals by minimising transfers, prompting the use of telehealth systems. In the field of neurology, telemedicine has been used in emergency settings for acute stroke management between spoke and hub hospital networks, where good outcomes have been achieved. However, data on the use of telemedicine in non-stroke acute neurological conditions accessing the emergency department (ED) are currently missing.Methods and analysesThis is an interventional, open-label trial on the use of teleconsultation in the ED for neurological diseases other than stroke. The study aims to develop a remote consultancy system (TeleNeurological Evaluation and Support, TeleNS) for patients with acute neurological symptoms referred to hospital facilities without a 24-hour availability of a neurologist consultant (spoke hospitals). The study population will include 100 ED patients referred to two spoke hospitals in 6 months, who will be asked to perform teleconsultation instead of inperson visits. As a control group, retrospectively available data from patients admitted to the ED of spoke hospitals during the same time period over the last 2 years will be evaluated. The primary objective is to assess whether a TeleNS for the ED guarantees a faster but qualitatively non-inferior diagnostic/therapeutic work-up if compared with inperson examination, assuring the availability of all the necessary examinations and treatments with consistent time-saving.Ethics and disseminationThe trial was designed following the national guidelines on clinical investigation on telemedicine provided by the Italian Ministry of Health and according to the Standard Protocol Items for Randomized Trials statement guidelines. This research protocol was approved by Comitato Etico Area Vasta Emilia Nord in September 2020 (number/identification: 942/2020/DISP/AOUMO SIRER ID 805) and was written without patient involvement. Patients’ associations will be involved in the dissemination of study design and results. The results of the study will be presented during scientific symposia or published in scientific journals.Trial registration numberNCT04611295.

Olanzapine for Prevention of Vomiting in Children and Adolescents Receiving Highly Emetogenic Chemotherapy: Investigator-Initiated, Randomized, Open-Label Trial

2020 ◽  
Vol 38 (32) ◽  
pp. 3785-3793 ◽  
Author(s):  
Ramavath D. Naik ◽  
Sreenivas V ◽  
Vishwajeet Singh ◽  
Ashwati S. Pillai ◽  
Deepa Dhawan ◽  
...  
Keyword(s):  
Safety Evaluation ◽  
Complete Response ◽  
Primary Objective ◽  
Emetogenic Chemotherapy ◽  
Control Group ◽  
Study Group ◽  
Open Label ◽  
Highly Emetogenic Chemotherapy ◽  
Acute Period ◽  
Open Label Trial

PURPOSE Chemotherapy-induced nausea and vomiting (CINV) is a significant toxicity of chemotherapy. Olanzapine is recommended in adult patients for the prevention of CINV but has not been prospectively investigated in children. METHODS This investigator-initiated, randomized, open-label trial evaluated olanzapine in children (ages 5-18 years) scheduled to receive the first cycle of highly emetogenic chemotherapy (HEC). All participants received aprepitant, ondansetron, and dexamethasone during and 2 days after chemotherapy. Participants in the study group additionally received oral olanzapine 0.14 mg/kg/day (rounded to the nearest 2.5 mg; maximum, 10 mg) during the chemotherapy block and 3 days postchemotherapy. The primary objective was to compare complete response (CR) rates (no vomiting and no rescue medication) between the groups in the acute, delayed, and overall periods. Nausea comparison and safety evaluation were secondary and additional objectives, respectively. The collection of outcomes and adverse events was performed daily until the completion of the overall period. RESULTS A total of 240 patients underwent randomization. We performed a modified intention-to-treat analysis on 231 patients (116 in the control group and 115 in the study group). A higher proportion of patients in the olanzapine group achieved CR in the acute period (78% v 59%; P = .001), delayed period (74% v 47%; P < .001) and overall period (64% v 38%; P < .001) than in the control group. The proportion of patients with no nausea was significantly higher in the olanzapine group in the acute period (74% v 52%; P < .001), delayed period (74% v 47%; P < .001), and overall period (64% v 37%; P < .001). Grade 1/2 somnolence was greater in the olanzapine group (35% v 11%; P < .001). There was no grade 3/4 somnolence reported. CONCLUSION Olanzapine significantly improved CR rates for vomiting in children receiving the first cycle of HEC.

302 A phase I trial of intratumoral PVSRIPO in patients with unresectable treatment refractory melanoma

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A329-A329
Author(s):  
Georgia Beasley ◽  
Nellie Farrow ◽  
Karenia Landa ◽  
Maria Angelica Seilm ◽  
Sin-Ho Jung ◽  
...  
Keyword(s):  
Phase I ◽  
Phase I Trial ◽  
Tumor Response ◽  
Clinical Investigation ◽  
Objective Response ◽  
Pathologic Complete Response ◽  
Disease Status ◽  
Primary Objective ◽  
Open Label ◽  
Preclinical Data

BackgroundWhile PD-1/PD-L1 antagonists have improved the prognosis for many patients with melanoma, the majority fail therapy. PVSRIPO is a novel immunotherapy consisting of a non-neurovirulent rhinovirus:poliovirus chimera that activates innate immunity to facilitate a targeted anti-tumor immune response. Preclinical data show that PVSRIPO plus anti-PD-1 therapy leads to a greater anti-tumor response than either agent alone, warranting clinical investigation.MethodsAn open-label phase I trial of intratumoral PVSRIPO in patients with unresectable melanoma (AJCC version 7 stage IIIB, IIIC, or IV) was performed. Eligible patients failed at least prior anti-PD-1 and BRAF/MEK (if BRAF mutant) therapy. The primary objective was to characterize the safety and tolerability of PVSRIPO. 12 patients in 4 cohorts received a total of 1, 2 (into 2 different lesions) or 3 (same lesion 3x or 3 different lesions) injections of PVSRIPO monotherapy, 21 days apart.ResultsPVSRIPO injections were well tolerated with no SAEs or DLTs reported; all TEAEs were grade (G) 1 or 2 (grade 1 pruritus most common at 58%), with all but 2 PVSRIPO-related TEAEs localized to the injected or adjacent lesions ( n=1 G1 hot flash, n=1 G1 fatigue). Despite the limited number of PVSRIPO treatments relative to the overall lesion burden (67% patients >5 lesions), 4 of 12 patients (33%) achieved an objective response per irRC, including 4/6 (66%) who received 3 injections (maximum administered). Pathologic complete response (ie, no viable tumor detected in injected and non-injected lesions biopsied) was observed in 2 of 4 (50%) patients with in-transit disease. PVSRIPO response relative to time since prior anti-PD-1 exposure is summarized in table 1. Following study completion/PVSRIPO therapy, 10/12 patients (83%) again received immune checkpoint inhibitor (ICI)-based therapy and 6/12 patients (50%) remained progression free at the data cutoff.Abstract 302 Table 1PVSRIPO anti-tumor response relative to ICI administration and post-study disease statusConclusionsIntratumoral PVSRIPO was well tolerated. When taken together with preclinical data, the anti-tumor responses observed relative to prior or subsequent ICI therapy suggests that PVSRIPO, either alone or in combination with anti-PD-1, may be an effective treatment in anti-PD-1 refractory melanoma. An amendment exploring higher PVSRIPO dose levels is ongoing and a phase 2 study with and without anti-PD-1 in the refractory population is initiating.Ethics ApprovalThis study (NCT03712358) was approved by WIRB; ID 20181772.

scholarly journals Phase I trial of intratumoral PVSRIPO in patients with unresectable, treatment-refractory melanoma

2021 ◽  
Vol 9 (4) ◽  
pp. e002203
Author(s):  
Georgia M Beasley ◽  
Smita K Nair ◽  
Norma E Farrow ◽  
Karenia Landa ◽  
Maria Angelica Selim ◽  
...  
Keyword(s):  
Adverse Events ◽  
Phase I ◽  
Phase I Trial ◽  
Clinical Investigation ◽  
Objective Response ◽  
Complete Response ◽  
Primary Objective ◽  
Mitogen Activated Protein Kinase ◽  
Open Label ◽  
Serious Adverse Events

BackgroundWhile programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) antagonists have improved the prognosis for many patients with melanoma, around 60% fail therapy. PVSRIPO is a non-neurovirulent rhinovirus:poliovirus chimera that facilitates an antitumor immune response following cell entry via the poliovirus receptor CD155, which is expressed on tumor and antigen-presenting cells. Preclinical studies show that oncolytic virus plus anti-PD-1 therapy leads to a greater antitumor response than either agent alone, warranting clinical investigation.MethodsAn open-label phase I trial of intratumoral PVSRIPO in patients with unresectable melanoma (American Joint Committee on Cancer V.7 stage IIIB, IIIC, or IV) was performed. Eligible patients had disease progression on anti-PD-1 and V-raf murine sarcoma viral oncogene homolog B (BRAF)/mitogen activated protein kinase kinase (MEK) inhibitors (if BRAF mutant). The primary objective was to characterize the safety and tolerability of PVSRIPO. Twelve patients in four cohorts received a total of 1, 2 or 3 injections of PVSRIPO monotherapy, with 21 days between injections.ResultsPVSRIPO injections were well tolerated with no serious adverse events (SAEs) or dose-limiting toxicities (DLTs) reported. All adverse events (AEs) were grade (G) 1 or G2 (G1 pruritus most common at 58%); all but two PVSRIPO-treatment related AEs were localized to the injected or adjacent lesions (n=1 G1 hot flash, n=1 G1 fatigue). Four out of 12 patients (33%) achieved an objective response per immune-related response criteria (two observations, 4 weeks apart), including 4/6 (67%) who received three injections. In the four patients with in-transit disease, a pathological complete response (pCR) was observed in two (50%) patients. Following study completion, 11/12 patients (92%) reinitiated immune checkpoint inhibitor-based therapy, and 6/12 patients (50%) remained without progression at a median follow-up time of 18 months.ConclusionIntratumoral PVSRIPO was well tolerated. Despite the limited number of PVSRIPO treatments relative to the overall lesion burden (67% patients>5 lesions), intratumoral PVSRIPO showed promising antitumor activity, with pCR in injected as well as non-injected lesions in select patients.Trial registration numberNCT03712358

scholarly journals COVID-19 Follow-App. Mobile App-Based Monitoring of COVID-19 Patients after Hospital Discharge: A Single-Center, Open-Label, Randomized Clinical Trial

2022 ◽  
Vol 12 (1) ◽  
pp. 24
Author(s):  
Ester Marquez-Algaba ◽  
Marc Sanchez ◽  
Maria Baladas ◽  
Claudia España ◽  
Hermes Salvatore Dallo ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Emergency Department ◽  
Hospital Discharge ◽  
Mobile App ◽  
Control Group ◽  
Primary Care Center ◽  
Open Label ◽  
Return Visits ◽  
Experimental Group

Introduction: In the midst of a pandemic, apps can be used to provide close follow-up, ensure that patients are monitored at home, avoid excessive pressure on medical facilities, prevent the movement of people (both patients and health professionals), and reduce the risk of infection. Objective: To adapt and validate the use of a smartphone application for outpatient follow-up of COVID-19 patients after hospital discharge. Methods: We conducted an open-label clinical trial at Hospital Universitari Vall d’Hebron in Barcelona, Spain. Patients were randomly assigned in a 1:1 ratio to be followed by the Farmalarm app or by their primary care center. The primary endpoint was the reduction in the need for in-person return visits. Results: From 31 March to 4 May 2020, 150 patients were enrolled in the study at hospital discharge: 74 patients were randomized to the experimental group, and 76 to the control group. All patients in the control group and all except for six in the experimental group completed the study. During hospitalization, before study inclusion, all but 4 (97.3%) had viral pneumonia, 91 (60.7%) required supplemental oxygen, and 16 (10.7%) required intensive care unit (ICU) admission. COVID-19–related return visits to the emergency department were significantly higher in the control group (7.9% vs. 0%; p = 0.028) in the per-protocol analysis. Telephone consultations with the emergency department were performed by 12 (15.8%) patients in the control group and 0 (0%) in the experimental group (p < 0.001). Satisfaction with outpatient monitoring was rated higher by the experimental group (5 vs. 4 points; p < 0.001). Conclusions: Following COVID-19 hospital discharge, home follow-up via a mobile app was effective in reducing in-person return visits without undermining patient satisfaction or perception of health, compared with standard follow-up.

scholarly journals Reactive Exercises with Interactive Objects: Interim Analysis of a Randomized Trial on Task-Driven NMES Grasp Rehabilitation for Subacute and Early Chronic Stroke Patients

Sensors ◽  
2021 ◽  
Vol 21 (20) ◽  
pp. 6739
Author(s):  
Andrea Crema ◽  
Ivan Furfaro ◽  
Flavio Raschellà ◽  
Mauro Rossini ◽  
Johannes Zajc ◽  
...  
Keyword(s):  
Acute Stroke ◽  
Technology Acceptance ◽  
Interim Analysis ◽  
Clinical Investigation ◽  
Training System ◽  
Control Group ◽  
Hand Rehabilitation ◽  
Stroke Patients ◽  
Open Label ◽  
Perceived Usability

Enriched environments and tools are believed to promote grasp rehabilitation after stroke. We designed S2, an interactive grasp rehabilitation system consisting of smart objects, custom orthoses for selective grasp constraining, and an electrode array system for forearm NMES. Motor improvements and perceived usability of a new enriched upper limb training system for sub-acute stroke patients was assessed in this interim analysis. Inclusion criteria: sub-acute stroke patients with MMSE>20, ipsilesional MI>80%, and contralesional MI<80%. Effects of 30-min therapy supplements, conventional vs. S2 prototype, are compared through a parallel two-arms dose-matched open-label trial, lasting 27 sessions. Clinical centres: Asklepios Neurologische Klinik Falkenstein, Königstein im Taunus, Germany, and Clinica Villa Beretta, Costa Masnaga, Italy. Assessment scales: ARAT, System Usability, and Technology Acceptance. Methodology: 26 participants were block randomized, allocated to the study (control N=12, experimental N=14) and underwent the training protocol. Among them, 11 participants with ARAT score at inclusion below 35, n = 6 in the experimental group, and n = 5 in the control group were analysed. Results: participants in the enriched treatment group displayed a larger improvement in the ARAT scale (+14.9 pts, pval=0.0494). Perceived usability differed between clinics. No adverse effect was observed in relation to the treatments. Trial status: closed. Conclusions: The S2 system, developed according to shared clinical directives, was tested in a clinical proof of concept. Variations of ARAT scores confirm the feasibility of clinical investigation for hand rehabilitation after stroke.

scholarly journals Early combination therapy with etanercept and methotrexate in JIA patients shortens the time to reach an inactive disease state and remission: results of a double-blind placebo-controlled trial

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Ekaterina Alexeeva ◽  
Gerd Horneff ◽  
Tatyana Dvoryakovskaya ◽  
Rina Denisova ◽  
Irina Nikishina ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Controlled Trial ◽  
Randomized Study ◽  
Primary Objective ◽  
Disease State ◽  
Inactive Disease ◽  
Open Label ◽  
Standard Regimen ◽  
Double Blind ◽  
Early Combination Therapy

Abstract Background Remission is the primary objective of treating juvenile idiopathic arthritis (JIA). It is still debatable whether early intensive treatment is superior in terms of earlier achievement of remission. The aim of this study was to evaluate the effectiveness of early etanercept+methotrexate (ETA+MTX) combination therapy versus step-up MTX monotherapy with ETA added in refractory disease. Methods A multi-centre, double-blind, randomized study in active polyarticular JIA patients treated with either ETA+MTX (n = 35) or placebo+MTX (n = 33) for up to 24 weeks, followed by a 24-week open-label phase. The efficacy endpoints included pedACR30 criteria improvement at week 12, inactive disease at week 24, and remission at week 48. Patients who failed to achieve the endpoints at week 12 or at week 24 escaped to open-label ETA+MTX. Safety was assessed at each visit. Results By intention-to-treat analysis, more patients in the ETA+MTX group reached the pedACR30 response at week 12 (33 (94.3%)) than in the placebo+MTX group (20 (60.6%); p = 0.001). At week 24, comparable percentages of patients reached inactive disease (11 (31.4%) vs 11 (33.3%)). At week 48, 11 (31.4%) and eight (24.2%) patients achieved remission. The median (+/−IQR) times to achieve an inactive disease state in the ETA+MTX and placebo+MTX groups were 24 (14–32) and 32 (24–40) weeks, respectively. Forty-four (74/100 patient-years) adverse events (AEs) were reported, leading to treatment discontinuation in 6 patients. Conclusions Early combination therapy with ETA+MTX proved to be highly effective compared to the standard step-up regimen. Compared to those treated with the standard regimen, more patients treated with a combination of ETA+MTX reached the pedACR30 response and achieved inactive disease and remission more rapidly.

Investigating the Impact of Cognitive Training for Individuals With Bothersome Tinnitus: A Randomized Controlled Trial

2021 ◽  
pp. 019459982199474
Author(s):  
Maggie Xing ◽  
Dorina Kallogjeri ◽  
Jay F. Piccirillo
Keyword(s):  
Randomized Controlled Trial ◽  
Cognitive Training ◽  
Mixed Model ◽  
Controlled Trial ◽  
Intervention Group ◽  
Control Group ◽  
Functional Index ◽  
Open Label ◽  
Randomized Controlled ◽  
The Impact

Objective To evaluate the effectiveness of cognitive training in improving tinnitus bother and to identify predictors of patient response. Study Design Prospective open-label randomized controlled trial. Setting Online. Methods Participants were adults with subjective idiopathic nonpulsatile tinnitus causing significant tinnitus-related distress. The intervention group trained by using auditory-intensive exercises for 20 minutes per day, 5 days per week, for 8 weeks. The active control group trained on the same schedule with non–auditory intensive games. Surveys were completed at baseline, 8 weeks, and 12 weeks. Results A total of 64 participants completed the study. The median age was 63 years (range, 25-69) in the intervention group and 61 years (34-68) in the control group. Mixed model analysis revealed that within-subject change in Tinnitus Functional Index in the intervention group was not different than the control group, with marginal mean differences (95% CI): 0.24 (–11.20 to 10.7) and 2.17 (–8.50 to 12.83) at 8 weeks and 2.33 (–8.6 to 13.3) and 3.36 (–7.91 to 14.6) at 12 weeks, respectively. When the 2 study groups were compared, the control group had higher Tinnitus Functional Index scores than the intervention group by 10.5 points at baseline (95% CI, –0.92 to 29.89), 8.1 at 8 weeks (95% CI, –3.27 to 19.42), and 9.4 at 12 weeks (95% CI, –2.45 to 21.34). Conclusion Auditory-intensive cognitive training was not associated with changes in self-reported tinnitus bother. Given the potential for neuroplasticity to affect tinnitus, we believe that future studies on cognitive training for tinnitus remain relevant.

scholarly journals A first-in-human, phase 1 study of the NEDD8 activating enzyme E1 inhibitor TAS4464 in patients with advanced solid tumors

2021 ◽  
Author(s):  
Noboru Yamamoto ◽  
Toshio Shimizu ◽  
Kan Yonemori ◽  
Shigehisa Kitano ◽  
Shunsuke Kondo ◽  
...  
Keyword(s):  
Liver Function ◽  
Solid Tumors ◽  
Dose Escalation ◽  
Enzyme Inhibitor ◽  
Phase 1 ◽  
Maximum Tolerated Dose ◽  
Primary Objective ◽  
Open Label ◽  
Phase 1 Study ◽  
Open Label Phase

SummaryBackground This open-label, phase 1 study investigated TAS4464, a potent NEDD8-activating enzyme inhibitor, in patients with advanced/metastatic solid tumors (JapicCTI-173,488; registered 13/01/2017). The primary objective was dose-limiting toxicities (DLTs). Maximum-tolerated dose (MTD) was investigated using an accelerated titration design. Methods The starting 10-mg/m2 dose was followed by an initial accelerated stage (weekly dosing; n = 11). Based on liver function test (LFT) results, a 14-day, 20-mg/m2 dose lead-in period was implemented (weekly dosing with lead-in; n = 6). Results Abnormal LFT changes and gastrointestinal effects were the most common treatment-related adverse events (AEs). DLTs with 56-mg/m2 weekly dosing occurred in 1/5 patients; five patients had grade ≥ 2 abnormal LFT changes at 40- and 56-mg/m2 weekly doses. Further dose escalation ceased because of the possibility of severe abnormal LFT changes occurring. DLTs with weekly dosing with lead-in occurred in 1/5 patients at a 56-mg/m2 dose; MTD could not be determined because discontinuation criteria for additional enrollment at that particular dose level were met. As no further enrollment at lower doses occurred, dose escalation assessment was discontinued. Serious treatment-related AEs, AEs leading to treatment discontinuation, and DLTs were all related to abnormal LFT changes, suggesting that TAS4464 administration could affect liver function. This effect was dose-dependent but considered reversible. Complete or partial responses to TAS4464 were not observed; one patient achieved prolonged stable disease. Conclusions MTD could not be determined due to TAS4464 effects on liver function. Further evaluation of the mechanism of NEDD8-activating enzyme inhibitor-induced abnormal liver function is required. Trial registration number JapicCTI-173,488 (registered with Japan Pharmaceutical Information Center). Registration date 13 January 2017

scholarly journals Effect of Whole-Body Cryotherapy on Morphological, Rheological and Biochemical Indices of Blood in People with Multiple Sclerosis

2021 ◽  
Vol 10 (13) ◽  
pp. 2833
Author(s):  
Bartłomiej Ptaszek ◽  
Aneta Teległów ◽  
Justyna Adamiak ◽  
Jacek Głodzik ◽  
Szymon Podsiadło ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Neurological Diseases ◽  
Venous Blood ◽  
Whole Body ◽  
Controlled Study ◽  
Control Group ◽  
Blood Indices ◽  
Rheological Indices ◽  
Whole Body Cryotherapy ◽  
The Impact

The aim of this study was to examine and assess the impact of a series of 20 whole-body cryotherapy (WBC) treatments on the biochemical and rheological indices of blood in people with multiple sclerosis. In this prospective controlled study, the experimental group consisted of 15 women aged 34–55 (mean age, 41.53 ± 6.98 years) with diagnosed multiple sclerosis who underwent a series of whole-body cryotherapy treatments. The first control group consisted of 20 women with diagnosed multiple sclerosis. This group had no intervention in the form of whole-body cryotherapy. The second control group consisted of 15 women aged 30–49 years (mean age, 38.47 ± 6.0 years) without neurological diseases and other chronic diseases who also underwent the whole-body cryotherapy treatment. For the analysis of the blood indices, venous blood was taken twice (first, on the day of initiation of whole-body cryotherapy treatments and, second, after a series of 20 cryotherapy treatments). The blood counts were determined using an ABX MICROS 60 hematological analyzer (USA). The LORCA analyzer (Laser–Optical Rotational Cell Analyzer, RR Mechatronics, the Netherlands) was used to study the aggregation and deformability of erythrocytes. The total protein serum measurement was performed using a Cobas 6000 analyzer, Roche and a Proteinogram-Minicap Sebia analyzer. Fibrinogen determinations were made using a Bio-Ksel, Chrom-7 camera. Statistically significant differences and changes after WBC in the levels of red blood cells (RBC), hemoglobin (HGB), hematocrit (HCT), elongation index, total extend of aggregation (AMP), and proteins (including fibrinogen) were observed. However, there was no significant effect of a series of 20 WBC treatments on changes in blood counts, rheology, and biochemistry in women with multiple sclerosis. Our results show that the use of WBC has a positive effect on the rheological properties of the blood of healthy women.

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