Preventing cardiomyopathy in DMD: A randomized, placebo-controlled drug-trial

2020 ◽  
pp. 10.1212/CPJ.0000000000001023
Author(s):  
John P. Bourke ◽  
Gillian Watson ◽  
Stefan Spinty ◽  
Andrew Bryant ◽  
Helen Roper ◽  
...  
Keyword(s):  
Adverse Event Reporting ◽  
Controlled Study ◽  
Lv Function ◽  
Cardiac Events ◽  
Serious Adverse Events ◽  
East Midlands ◽  
Heart Study ◽  
Parallel Group ◽  
Class 1

AbstractObjective:To determine whether a combination of two heart medications would be tolerated and could prevent / delay the onset of cardiomyopathy in boys with DMD compared to placebo.Methods:This multi-centre, parallel group,1:1 patient randomised, placebo-controlled study of prophylactic perindopril and bisoprolol recruited boys with DMD aged 5-13 years, with normal ventricular function. Repeat assessments of LV-function, ECG and Adverse Event reporting were performed six-monthly. The primary outcome was change in ejection fraction between arms after 36 months. The study was approved by the NRES Committee East Midlands - Derby.Results:Eighty-five boys were recruited (76% on steroid therapy) and randomised to combination heart drugs or matched placebo. Group change in LVEF% at 36 months from baseline was -2.2 + 6.0% and -2.9 + 6.1% in active and placebo arms (adjusted mean difference: -2.1, 95% CI -5.2 to 1.1). There was no difference between arms over repeated assessments (ANOVA) up to 36 months (trial arms p = 0.53); arm-over-time (p = 0.44). Four participants on placebo but none on active therapy were withdrawn due to deteriorations in LV-function. Secondary outcomes did not differ between arms either. Thirty-six Serious Adverse Events occurred none due to cardiac events or trial medication.Conclusions:Combination therapy was well tolerated. Consistent with the previous prophylactic perindopril heart study, there was no evidence of group benefit after 36-months treatment.Classification of evidence:This study provides Class 1 evidence that combination perindopril-bisoprolol therapy was well tolerated but did not change decline in LVEF significantly in boys with DMD.

scholarly journals Effect of cardiosphere-derived cells on segmental myocardial function after myocardial infarction: ALLSTAR randomised clinical trial

Open Heart ◽  
2021 ◽  
Vol 8 (2) ◽  
pp. e001614
Author(s):  
Mohammad R Ostovaneh ◽  
Raj R Makkar ◽  
Bharath Ambale-Venkatesh ◽  
Deborah Ascheim ◽  
Tarun Chakravarty ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Clinical Trial ◽  
Myocardial Function ◽  
Randomised Clinical Trial ◽  
Scar Tissue ◽  
Left Ventricular ◽  
Lv Function ◽  
Cardiac Events ◽  
Lv Dysfunction ◽  
Registration Number

BackgroundMost cell therapy trials failed to show an improvement in global left ventricular (LV) function measures after myocardial infarction (MI). Myocardial segments are heterogeneously impacted by MI. Global LV function indices are not able to detect the small treatment effects on segmental myocardial function which may have prognostic implications for cardiac events. We aimed to test the efficacy of allogeneic cardiosphere-derived cells (CDCs) for improving regional myocardial function and contractility.MethodsIn this exploratory analysis of a randomised clinical trial, 142 patients with post-MI with LVEF <45% and 15% or greater LV scar size were randomised in 2:1 ratio to receive intracoronary infusion of allogenic CDCs or placebo, respectively. Change in segmental myocardial circumferential strain (Ecc) by MRI from baseline to 6 months was compared between CDCs and placebo groups.ResultsIn total, 124 patients completed the 6-month follow-up (mean (SD) age 54.3 (10.8) and 108 (87.1%) men). Segmental Ecc improvement was significantly greater in patients receiving CDC (−0.5% (4.0)) compared with placebo (0.2% (3.7), p=0.05). The greatest benefit for improvement in segmental Ecc was observed in segments containing scar tissue (change in segmental Ecc of −0.7% (3.5) in patients receiving CDC vs 0.04% (3.7) in the placebo group, p=0.04).ConclusionsIn patients with post-MI LV dysfunction, CDC administration resulted in improved segmental myocardial function. Our findings highlight the importance of segmental myocardial function indices as an endpoint in future clinical trials of patients with post-MI.Trial registration numberNCT01458405.

scholarly journals Coaxial Access for Microcatheter Stabilization During Aneurysm Coiling: 2-Dimensional Operative Video

2021 ◽  
Author(s):  
Miri Kim ◽  
Rachyl Shanker ◽  
Anthony Kam ◽  
Matthew Reynolds ◽  
Joseph C Serrone
Keyword(s):  
Artery Aneurysm ◽  
Anterior Communicating Artery ◽  
Distal Catheter ◽  
Anterior Communicating Artery Aneurysm ◽  
Class 1 ◽  
Previously Treated ◽  
Aneurysm Occlusion ◽  
Intracranial Circulation ◽  
Aneurysm Coiling

Abstract Coaxial support is a fundamental technique utilized by neurointerventionalists to optimize distal catheter control within the intracranial circulation. Here we present a 41-yr-old woman with a previously coiled ruptured anterior communicating artery aneurysm with progressive recurrence harboring tortuous internal carotid anatomy to demonstrate the utility of coaxial support. Raymond-Roy classification of initial aneurysm coiling of class 1 resulted as class 3b over the 21 mo from initial treatment.1 The patient consented to stent-assisted coiling for retreatment of this aneurysm. Coaxial support was advanced as distally as possible in the proximal vasculature to improve catheter control, reducing dead space within which the microcatheter could move, decreasing angulations within proximal vasculature, limiting the movement of the native vessels, and providing a surface of lower friction than the endothelium. As the risk of recurrent subarachnoid hemorrhage in previously treated coiled aneurysms approaches 3%, retreatment occurs in 16.4% within 6 yr2 and in 17.4% of patients within 10 yr.3 Rerupture is slightly higher in patients who underwent coiling vs clipping, with the rerupture risk inversely proportional to the degree of aneurysm occlusion,4 further substantiating that coaxial support provides technical advantage in selected patients where additional microcatheter control is necessary for optimal occlusion. Pitfalls of this technique include vasospasm and vascular injury, which can be ameliorated by pretreatment of the circulation with vasodilators to prevent catheter-induced vasospasm. This case and model demonstration illustrates the technique of coaxial access in the stent-assisted coiling of a recurrent anterior communicating artery aneurysm and identification and management of catheter-induced vasospasm.

scholarly journals Mii-vitaliSe: a pilot randomised controlled trial of a home gaming system (Nintendo Wii) to increase activity levels, vitality and well-being in people with multiple sclerosis

BMJ Open ◽  
2017 ◽  
Vol 7 (9) ◽  
pp. e016966 ◽  
Author(s):  
Sarah Thomas ◽  
Louise Fazakarley ◽  
Peter W Thomas ◽  
Sarah Collyer ◽  
Sarah Brenton ◽  
...  
Keyword(s):  
Physical Activity ◽  
Multiple Sclerosis ◽  
Controlled Trial ◽  
Well Being ◽  
Recruitment Rate ◽  
Controlled Study ◽  
Activity Levels ◽  
Nintendo Wii ◽  
Serious Adverse Events ◽  
Randomised Controlled

ObjectivesWhile the health and well-being benefits of physical activity are recognised, people with multiple sclerosis (MS) often face greater barriers than the general population. The Nintendo Wii potentially offers a fun, convenient way of overcoming some of these. The aim was to test the feasibility of conducting a definitive trial of the effectiveness and cost-effectiveness of Mii-vitaliSe; a home-based, physiotherapist-supported Nintendo Wii intervention.DesignA single-centre wait-list randomised controlled study.SettingMS service in secondary care.ParticipantsAmbulatory, relatively inactive people with clinically confirmed MS.InterventionThirty participants were randomised to receive Mii-vitaliSe either immediately (for 12 months) or after a 6-month wait (for 6 months). Mii-vitaliSe consisted of two supervised Nintendo Wii familiarisation sessions in the hospital followed by home use (Wii Sports, Sports Resort and Fit Plus software) with physiotherapist support and personalised resources.OutcomesIncluded self-reported physical activity levels, quality of life, mood, self-efficacy, fatigue and assessments of balance, gait, mobility and hand dexterity at baseline, 6 and 12 months. Interviews (n=25) explored participants’ experiences and, at study end, the two Mii-vitaliSe facilitators’ experiences of intervention delivery (main qualitative findings reported separately).ResultsMean (SD) age was 49.3 (8.7) years, 90% female, with 47% diagnosed with MS <6 years ago and 60% new to active gaming. The recruitment rate was 31% (95% CI 20% to 44%). Outcome data were available for 29 (97%) at 6 months and 28 (93%) at 12 months. No serious adverse events were reported during the study. Qualitative data indicated that Mii-vitaliSe was well-received. Mean Wii use across both groups over the initial 6-month intervention period was twice a week for 27 min/day. Mean cost of delivering Mii-vitaliSe was £684 per person.DiscussionMii-vitaliSe appears acceptable and a future trial feasible and warranted. These findings will inform its design.Trial registrationISRCTN49286846

scholarly journals Effectiveness of brushing teeth in patients with reduced oral hygiene by laypeople: a randomized, controlled study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Anna Greta Barbe ◽  
Aya Al-Barwari ◽  
Stefanie Hamacher ◽  
Renate Deinzer ◽  
Ulrike Weik ◽  
...  
Keyword(s):  
Oral Hygiene ◽  
Group Intervention ◽  
Controlled Study ◽  
Care Gap ◽  
Parallel Group ◽  
Dental Professional ◽  
The Individual ◽  
Time Required ◽  
Powered Toothbrush ◽  
Dental Professionals

Abstract Background To evaluate the success of plaque reduction after external toothbrushing by instructed laypeople versus dental professionals using either a manual or powered toothbrush. Longitudinal, randomized, parallel-group intervention study in periodontitis patients with reduced oral hygiene quality undergoing anti-infective therapy. Patients were randomly and equally assigned to one of four groups: laypeople using a manual or powered toothbrush or dental professionals using a manual or powered toothbrush. Plaque reduction (Quigley–Hein-Index (QHI), Marginal Plaque Index (MPI)), gingivitis (papilla bleeding index), and cleaning time (seconds) were investigated. Results Thirty-nine patients participated in the study. Neither the choice of toothbrush (p = 0.399) nor the use of a dental professional (p = 0.790) had a significant influence on plaque levels achieved. However, multivariate modeling indicated statistically significant differences in the external cleaning time between brushing groups, with longer time required by laypeople (p = 0.002) and longer use of the powered toothbrush (p = 0.024). Conclusion When the ability to carry out personal oral hygiene is reduced, external brushing by dental professionals or instructed laypeople who meet previously defined criteria such as sufficient personal oral hygiene at home could help to fill the emerging dental care gap. A combination of oral hygiene approaches adapted to the individual needs of the patients in need of external help is necessary for optimum oral hygiene. Trial registration: German Clinical Trials register (https://www.germanctr.de; number DRKS00018779; date of registration 04/11/2019).

Acetyl L-Carnitine Slows Decline in Younger Patients With Alzheimer's Disease: A Reanalysis of a Double-Blind, Placebo-Controlled Study Using the Trilinear Approach

1998 ◽  
Vol 10 (2) ◽  
pp. 193-203 ◽  
Author(s):  
John O. Brooks ◽  
Jerome A. Yesavage ◽  
Angelico Carta ◽  
Daniele Bravi
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Average Rate ◽  
The United States ◽  
Rate Of Change ◽  
Disease Assessment ◽  
Controlled Study ◽  
Double Blind ◽  
Parallel Group ◽  
Longitudinal Effects

Objectives: To assess the longitudinal effects of acetyl-L-carnitine (ALC) on patients diagnosed with Alzheimer's disease. Design: Longitudinal, double-blind, parallel-group, placebocontrolled. Setting: Twenty-four outpatient sites across the United States. Participants: A total of 334 subjects diagnosed with probable Alzheimer's disease by NINCDS-ADRDA criteria. These data were originally reported by Thal and colleagues (1996). Measurements: Cognitive subscale of the Alzheimer Disease Assessment Scale (ADAS) given every 3 months for 1 year. Results: The average rate of change was estimated using the trilinear approach, which allows for periods of both change and stability. Both the ALC group and the placebo group exhibited the same mean rate of change on the ADAS (0.68 points/month). However, a multiple regression analysis revealed a statistically significant Age × Drug interaction characterized by younger subjects benefiting more from ALC treatment than older subjects. Further analyses suggested that the optimal, though not statistically significant, cutpoint for ALC benefit was 61 years of age. Conclusions: ALC slows the progression of Alzheimer's disease in younger subjects, and the use of the trilinear approach to estimate the average rate of change may prove valuable in pharmacological trials.

scholarly journals Safety, Immunogenicity, and Antibody Persistence following an Investigational Streptococcus pneumoniae and Haemophilus influenzae Triple-Protein Vaccine in a Phase 1 Randomized Controlled Study in Healthy Adults

2013 ◽  
Vol 21 (1) ◽  
pp. 56-65 ◽  
Author(s):  
Johan Berglund ◽  
Peter Vink ◽  
Fernanda Tavares Da Silva ◽  
Pascal Lestrate ◽  
Dominique Boutriau
Keyword(s):  
T Cell ◽  
Haemophilus Influenzae ◽  
Phase 1 ◽  
Geometric Mean ◽  
Controlled Study ◽  
Protein Vaccine ◽  
Serious Adverse Events ◽  
Content Type ◽  
Antibody Persistence ◽  
Systemic Symptoms

ABSTRACTWe investigated a protein-based nontypeableHaemophilus influenzae(NTHi) and pneumococcal (HiP) vaccine containing pneumococcal histidine triad D (PhtD), detoxified pneumolysin (dPly), and NTHi protein D (PD) in adults. In a phase I study, 40 healthy 18- to 40-year-old subjects were randomized (2:2:1) to receive two HiP doses administered 60 days apart, with or without AS03 adjuvant (HiP-AS and HiP groups, respectively), or Engerix B (GlaxoSmithKline, Belgium) as a control. Safety, antibodies, and antigen-specific CD4+T-cell immune responses were assessed before and until 480 days after vaccination. No serious adverse events were reported, and no subject withdrew due to an adverse event. Local and systemic symptoms were reported more frequently in the HiP-AS group than in the other two groups. The frequency and intensity of local and systemic symptoms appeared to increase after the second dose of HiP-AS or HiP but not Engerix B. Antibody geometric mean concentrations (GMCs) for PhtD, dPly, and PD increased after each dose of HiP-AS or HiP, with higher GMCs being observed in the HiP-AS group (statistically significant for anti-PD after dose 1 and anti-Ply after dose 2). GMCs remained higher at day 420 than prior to vaccination in both the HiP-AS and HiP groups. Antigen-specific CD4+T cells increased after each dose but were unmeasurable by day 480. Two doses of an investigational PhtD-dPly-PD protein vaccine induced humoral immunity and antigen-specific CD4+T-cell responses after each dose, with generally higher responses when the vaccine was administered with AS03. HiP combined with AS03 appeared to be more reactogenic than the antigens alone. (This study has been registered at ClinicalTrials.gov under registration no. NCT00814489.)

scholarly journals A Classification of Baire Class 1 Functions

1990 ◽  
Vol 318 (1) ◽  
pp. 209 ◽  
Author(s):  
A. S. Kechris ◽  
A. Louveau
Keyword(s):  
Baire Class ◽  
Class 1
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