Retrospective analysis of the effectiveness of a reduced dose of idarucizumab in dabigatran reversal

2021 ◽  
Author(s):  
Louisa Stone ◽  
Eileen Merriman ◽  
Gordon Royle ◽  
Merit Hanna ◽  
Henry Chan
Keyword(s):  
Dose Group ◽  
Primary Outcome ◽  
Dabigatran Etexilate ◽  
Clinical Effectiveness ◽  
Similar Proportion ◽  
Published Data ◽  
Reversal Agent ◽  
Reduced Dose ◽  
Real World Setting ◽  
Urgent Procedure

Background The recommended dose of idarucizumab, the specific reversal agent for dabigatran etexilate, is 5g. However, published data showed biochemical reversal after an initial 2.5g dose. Objectives This study aims to retrospectively compare the clinical effectiveness of 2.5g and 5g doses of idarucizumab used in dabigatran reversal in three hospitals in Auckland, New Zealand. Methods All patients receiving idarucizumab for dabigatran reversal between 1st April 2016 and 31st December 2018 were included. The primary outcome was the likelihood of receiving a second dose of idarucizumab during the same admission. Secondary outcomes included normalisation of coagulation profiles; and 30-day thrombotic, bleeding and mortality rates. Results Of 329 patients included, 206 received an upfront 2.5g dose and 123 received a 5g dose. The median age was 78 years and median creatinine clearance was 50mL/min. Most patients (62.6%) required idarucizumab for an urgent procedure, while 37.4% presented with bleeding. A 2.5g dose was not associated with an increased rate of receiving a second dose (OR 0.686, 95% CI 0.225-2.090). A similar proportion of patients in each group achieved a normal APTT (73.8% vs 80.0%, p=0.464) and dTCT (95.9% vs 91.4%, p=0.379) following idarucizumab infusion. There was no increase in the rate of death (OR 0.602, 95% CI 0.292-1.239), thrombosis (OR 0.386, 95% CI 0.107-1.396) or bleeding (OR 0.96, 95% CI 0.27-3.33) in the 2.5g dose group compared to the 5g dose group. Conclusions An initial 2.5g dose of idarucizumab appears effective for dabigatran reversal in the real-world setting.

scholarly journals Haemodynamic effects of a prehospital emergency anaesthesia protocol consisting of fentanyl, ketamine and rocuronium in patients with trauma: a retrospective analysis of data from a Helicopter Emergency Medical Service

BMJ Open ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. e056487
Author(s):  
Ewoud ter Avest ◽  
Dassen Ragavan ◽  
Joanne Griggs ◽  
Michael Dias ◽  
Sophie A Mitchinson ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Emergency Medical Service ◽  
Dose Group ◽  
Primary Outcome ◽  
Medical Service ◽  
Helicopter Emergency Medical Service ◽  
Trauma Patients ◽  
Full Dose ◽  
Reduced Dose ◽  
Blood Pressures

ObjectivesPrehospital rapid sequence induction (RSI) of anaesthesia is an intervention with significant associated risk. In this study, we aimed to investigate the haemodynamic response over time of a prehospital RSI protocol of fentanyl, ketamine and rocuronium in a heterogeneous population of trauma patients.Design, setting and participantWe performed a retrospective study of all trauma patients who received a prehospital RSI for trauma by a physician staffed Helicopter Emergency Medical Service in the UK between 1 June 2018 and 1 February 2020.Primary outcome measurePrimary outcome was defined as the incidence of clinically relevant hypotensive (systolic blood pressure (SBP) or mean arterial pressure (MAP) >20% below baseline, with an absolute SBP <90 mm Hg or MAP <65 mm Hg) or hypertensive (SBP or MAP >20% above baseline) episodes in the first 10 minutes post-RSI.ResultsIn total, 322 patients were included. 204 patients (63%) received a full-dose induction of 3 μg/kg fentanyl, 2 mg/kg ketamine and 1 mg/kg rocuronium, whereas 128 patients (37%) received a reduced-dose induction. Blood pressures decreased on average 12 mm Hg (95% CI 7 to 16) in the full-dose group and 6 mm Hg (95% CI 1 to 11) in the reduced-dose group, p=0.10). A hypotensive episode (mean SBP drop 53 mm Hg) was noted in 29 patients: 17 (8.3%) receiving a full dose and 12 (10.2%) receiving a reduced-dose induction, p=0.69. The blood pressure nadir was recorded on average 6–8 min after RSI. A hypertensive episode was present in 22 patients (6.8%). The highest blood pressures were recorded in the first 3 min after RSI.ConclusionPrehospital induction of anaesthesia for trauma with fentanyl, ketamine and rocuronium is not related to a significant change in haemodynamics in most patients. However, a (delayed) hypotensive response with a significant drop in SBP should be anticipated in a minority of patients irrespective of the dose regimen chosen.

scholarly journals Real-World Clinical Outcomes Associated with Canagliflozin in Patients with Type 2 Diabetes Mellitus in Spain: The Real-Wecan Study

2020 ◽  
Vol 9 (7) ◽  
pp. 2275
Author(s):  
Juan J. Gorgojo-Martínez ◽  
Manuel A. Gargallo-Fernández ◽  
Alba Galdón Sanz-Pastor ◽  
Teresa Antón-Bravo ◽  
Miguel Brito-Sanfiel ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Real World ◽  
Primary Outcome ◽  
Baseline Hba1c ◽  
Real World Setting ◽  
Antihyperglycemic Therapy ◽  
The Mean ◽  
Hba1c Levels

The aims of this multicentric retrospective study were to assess in a real-world setting the effectiveness and safety of canagliflozin 100 mg/d (CANA100) as an add-on to the background antihyperglycemic therapy, and to evaluate the intensification of prior sodium–glucose co-transporter type 2 inhibitor (SGLT-2i) therapy by switching to canagliflozin 300 mg/d (CANA300) in patients with T2DM. One cohort of SGLT2i-naïve patients with T2DM who were initiated on CANA100 and a second cohort of patients with prior background SGLT-2i therapy who switched to CANA300 were included in the study. The primary outcome of the study was the mean change in HbA1c over the follow-up time. In total, 583 patients were included—279 in the cohort of CANA100 (HbA1c 8.05%, weight 94.9 kg) and 304 in the cohort of CANA300 (HbA1c 7.51%, weight 92.0 kg). Median follow-up periods in both cohorts were 9.1 and 15.4 months respectively. CANA100 was associated to significant reductions in HbA1c (−0.90%) and weight (−4.1 kg) at the end of the follow-up. In those patients with baseline HbA1c > 8% (mean 9.25%), CANA100 lowered HbA1c levels by 1.51%. In the second cohort, patients switching to CANA300 experienced a significant decrease in HbA1c (−0.35%) and weight (−2.1 kg). In those patients with baseline HbA1c > 8% (mean 8.94%), CANA300 lowered HbA1c levels by 1.12%. There were significant improvements in blood pressure in both cohorts. No unexpected adverse events were reported. In summary, CANA100 (as an add-on therapy) and CANA300 (switching from prior SGLT-2i therapy) significantly improved several cardiometabolic parameters in patients with T2DM.

scholarly journals Lactobacillus Kefiri LKF01 (Kefibios®) for Prevention of Diarrhoea in Cancer Patients Treated with Chemotherapy: A Prospective Study

Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 385
Author(s):  
Michele Ghidini ◽  
Mariaceleste Nicoletti ◽  
Margherita Ratti ◽  
Gianluca Tomasello ◽  
Veronica Lonati ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Prospective Observational Study ◽  
Primary Outcome ◽  
Final Analysis ◽  
Clinical Effectiveness ◽  
High Grade ◽  
Combination Therapies ◽  
Grade 3 ◽  
Lactobacillus Kefiri ◽  
A Prospective Study

Diarrhoea is one of the main side effects that cancer patients face. The literature showsthat the incidence of chemotherapy (CT)-induced diarrhoea (grade 3–4) in treated patients is in the range of 10–20%, particularly after 5-fluorouracil (5-FU) bolus or some combination therapies of irinotecan and fluoropyrimidines. The aim of the present study was to evaluate the clinical effectiveness of Lactobacillus kefiri LKF01 (Kefibios®) in the prevention or treatment of CT-related diarrhoea in the cancer population. We conducted a prospective observational study. Patients enrolled were adults treated for at least four months with 5-FU-based CT. Kefibios® was administered to patients every day. The primary outcome was the evaluation of the incidence of grade 3–4 CT-induced diarrhoea. We included 76 patients in the final analysis. A 6.6% incidence of high-grade diarrhoea was found in the evaluated population (4.7% of patients treated with 5-FU-based therapy and 8.5% of patients treated with capecitabine-based CT). The overall incidence of high-grade diarrhoea observed was higher in the 1st and 2nd cycles (3.9%), with a subsequent sharp reduction from the 3rd cycle (1.3%) and negativisation from the 5th cycle. Lactobacillus kefiri LKF01 (Kefibios®) is safe and effective in preventing severe diarrhoea in cancer patients receiving 5-FU or capecitabine-based treatment.

Abstract P467: Clinical Effectiveness of Endovascular Stroke Treatment in the Early and Extended Time Windows

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Raul Nogueira ◽  
Diogo C Haussen ◽  
David S Liebeskind ◽  
Tudor G Jovin ◽  
Rishi Gupta ◽  
...  
Keyword(s):  
Randomized Clinical Trials ◽  
Time Windows ◽  
Clinical Effectiveness ◽  
Inclusion Criteria ◽  
Open Label ◽  
Time To Treatment ◽  
Stroke Treatment ◽  
Real World Setting ◽  
Lower Baseline ◽  
Iv Tpa

Background and Purpose: The clinical efficacy of mechanical thrombectomy (MT) has been unequivocally demonstrated in multiple randomized clinical trials (RCTs). However, these studies were performed in carefully selected centers and utilized strict inclusion criteria. We aim to assess the clinical effectiveness of MT by comparing the specific RCT populations with corresponding patient cohorts derived from a prospective registry. Methods: A total of 2008 patients from 76 sites across 12 countries were enrolled in a prospective open-label MT registry. Patients were categorized into the corresponding cohorts of the SWIFT-Prime, DAWN, and DEFUSE 3 trials based on the age, baseline NIHSS, occlusion site, IV tPA use, pre-morbid mRS and time to treatment criteria used in the RCTs without considering specific parenchymal imaging findings. Baseline and outcome variables were compared across the corresponding groups. Results: As compared to the treated patients in the actual trials, registry-derived patients tended to be younger and had lower baseline ASPECTS. In addition, time to treatment was earlier and the use of IV tPA and general anesthesia were higher in DAWN- and DEFUSE 3-registry derived patients versus their corresponding trials. Reperfusion rates were higher in the registry patients. The rates of 90-day good outcome (mRS 0-2) in registry-derived patients were comparable to those of the patients treated in the corresponding RCTs (SWIFT-Prime, 64.5% vs 60.2%; DAWN, 50.4% vs 48.6%; Beyond-DAWN: 52.4% vs 48.6%; DEFUSE 3, 52% vs 44.6%, respectively; all P>0.05). Registry-derived patients had significant less disability than the corresponding RCT controls (ordinal mRS shift OR, P <0.05 for all). Conclusion: Our study provides favorable generalizability data for the safety and efficacy of thrombectomy in the “real-world” setting and supports that patients may be safely treated outside the constraints of RCTs and strict guidelines.

scholarly journals Estimation of the effect size of clinical intervention in otorhinolaryngology

2020 ◽  
Vol 19 (2) ◽  
pp. 42-50
Author(s):  
A. A. Korneenkov ◽  
◽  
I. V. Fanta ◽  
Keyword(s):  
Local Anesthesia ◽  
Effect Size ◽  
Quantitative Methods ◽  
Clinical Intervention ◽  
Clinical Effectiveness ◽  
Relative Effect ◽  
Therapeutic Modality ◽  
Published Data ◽  
Therapeutic Effects ◽  
Clinical Effects

The article discusses the concepts of measures of the effect of clinical effects, quantitative methods for their calculation and interpretation, their importance for making medical decisions. Algorithms for calculating effect measures are described for different clinical trial endpoints represented by quantitative (numerical) or binary types of variables, and for different types of effect size indicator (absolute, relative effect size, or clinical effectiveness indicator). It is shown that in the context of assessing the effect of therapeutic effects and clinical efficacy in general, measuring the size of the effect provides a valuable tool for data analysis. Evaluation and interpretation of the effect of the therapeutic modality only on the basis of the level of significance p obtained by testing statistical hypotheses without specifying the size of the effect is not sufficient to understand the importance of using the effect in clinical practice. To obtain an adequate quantitative assessment of the effect and its interpretation, the concept of the size of the effect is a convenient system of methods that is widely used. To illustrate the calculation and interpretation of the size of the effect, published data from clinical studies of the effectiveness of local anesthesia to reduce pain after septoplasty were used. It is shown how, using the presented technique, it is possible to efficiently calculate and easily interpret measures of the effect of the application of local anesthesia. All calculations were performed in the statistical program R.

scholarly journals Clinical effectiveness and cost-effectiveness of a multifaceted podiatry intervention for falls prevention in older people: a multicentre cohort randomised controlled trial (the REducing Falls with ORthoses and a Multifaceted podiatry intervention trial)

2017 ◽  
Vol 21 (24) ◽  
pp. 1-198 ◽  
Author(s):  
Sarah Cockayne ◽  
Sara Rodgers ◽  
Lorraine Green ◽  
Caroline Fairhurst ◽  
Joy Adamson ◽  
...  
Keyword(s):  
Cost Effectiveness ◽  
Usual Care ◽  
Incidence Rate ◽  
Primary Outcome ◽  
Controlled Trial ◽  
Intervention Group ◽  
Clinical Effectiveness ◽  
Cost Effective ◽  
Falls Prevention ◽  
Randomised Controlled

BackgroundFalls are a serious cause of morbidity and cost to individuals and society. Evidence suggests that foot problems and inappropriate footwear may increase the risk of falling. Podiatric interventions could help reduce falls; however, there is limited evidence regarding their clinical effectiveness and cost-effectiveness.ObjectivesTo determine the clinical effectiveness and cost-effectiveness of a multifaceted podiatry intervention for preventing falls in community-dwelling older people at risk of falling, relative to usual care.DesignA pragmatic, multicentred, cohort randomised controlled trial with an economic evaluation and qualitative study.SettingNine NHS trusts in the UK and one site in Ireland.ParticipantsIn total, 1010 participants aged ≥ 65 years were randomised (intervention,n = 493; usual care,n = 517) via a secure, remote service. Blinding was not possible.InterventionsAll participants received a falls prevention leaflet and routine care from their podiatrist and general practitioner. The intervention also consisted of footwear advice, footwear provision if required, foot orthoses and foot- and ankle-strengthening exercises.Main outcome measuresThe primary outcome was the incidence rate of falls per participant in the 12 months following randomisation. The secondary outcomes included the proportion of fallers and multiple fallers, time to first fall, fear of falling, fracture rate, health-related quality of life (HRQoL) and cost-effectiveness.ResultsThe primary analysis consisted of 484 (98.2%) intervention and 507 (98.1%) usual-care participants. There was a non-statistically significant reduction in the incidence rate of falls in the intervention group [adjusted incidence rate ratio 0.88, 95% confidence interval (CI) 0.73 to 1.05;p = 0.16]. The proportion of participants experiencing a fall was lower (50% vs. 55%, adjusted odds ratio 0.78, 95% CI 0.60 to 1.00;p = 0.05). No differences were observed in key secondary outcomes. No serious, unexpected and related adverse events were reported. The intervention costs £252.17 more per participant (95% CI –£69.48 to £589.38) than usual care, was marginally more beneficial in terms of HRQoL measured via the EuroQoL-5 Dimensions [mean quality-adjusted life-year (QALY) difference 0.0129, 95% CI –0.0050 to 0.0314 QALYs] and had a 65% probability of being cost-effective at the National Institute for Health and Care Excellence threshold of £30,000 per QALY gained. The intervention was generally acceptable to podiatrists and trial participants.LimitationsOwing to the difficulty in calculating a sample size for a count outcome, the sample size was based on detecting a difference in the proportion of participants experiencing at least one fall, and not the primary outcome. We are therefore unable to confirm if the trial was sufficiently powered for the primary outcome. The findings are not generalisable to patients who are not receiving podiatry care.ConclusionsThe intervention was safe and potentially effective. Although the primary outcome measure did not reach significance, a lower fall rate was observed in the intervention group. The reduction in the proportion of older adults who experienced a fall was of borderline statistical significance. The economic evaluation suggests that the intervention could be cost-effective.Future workFurther research could examine whether or not the intervention could be delivered in group sessions, by physiotherapists, or in high-risk patients.Trial registrationCurrent Controlled Trials ISRCTN68240461.FundingThis project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full inHealth Technology Assessment; Vol. 21, No. 24. See the NIHR Journals Library website for further project information.

A Low-Dose 4F-PCC Protocol for DOAC-Associated Intracranial Hemorrhage

2019 ◽  
Vol 35 (11) ◽  
pp. 1203-1208 ◽  
Author(s):  
Karen Berger ◽  
Melissa Santibañez ◽  
Lina Lin ◽  
Christine A. Lesch
Keyword(s):  
Intracranial Hemorrhage ◽  
Primary Outcome ◽  
Low Dose ◽  
Oral Anticoagulants ◽  
Secondary Outcome ◽  
Thrombotic Risk ◽  
Real World Setting ◽  
Direct Acting ◽  
Current Guidelines ◽  
Direct Acting Oral Anticoagulants

Purpose: Current guidelines favor 4F-PCC over plasma for reversal of warfarin. Uncertainty remains on the hemostatic effectiveness and thrombotic risk of 4F-PCC for direct-acting oral anticoagulants (DOACs), particularly in patients with intracranial hemorrhage (ICH). This study sought to evaluate the effectiveness and safety of a lower dose protocol of 25 units/kg 4F-PCC for the management of DOAC-associated ICH in a real-world setting. Materials and Methods: This was a retrospective study of adult patients who received at least one dose of 4F-PCC from March 2014 to December 2015 for DOAC-associated ICH. The primary outcome was hemostatic effectiveness within 24 hours. The secondary outcome was thromboembolic events within 14 days. Results: Twenty-two patients received 4F-PCC for DOAC-associated ICH and were included in the analysis. Hemostasis was evaluable in 19 patients with post-4F-PCC imaging available and occurred in 18/19 (94.7%) patients. Thromboembolism occurred in 2 out of 22 patients (9.1%). Conclusions: The use of a lower dose protocol of 25 units/kg of 4F-PCC resulted in high rates of hemostasis in patients with DOAC-associated ICH. Two patients developed thrombotic events within 14 days of 4F-PCC administration.

scholarly journals Retrospective Assessment of the Efficacy of Modified Progressive Tinnitus Management Skills Education in a Military Medical Treatment Facility

2019 ◽  
Vol 184 (9-10) ◽  
pp. e468-e473 ◽  
Author(s):  
LaGuinn P Sherlock ◽  
Candice E Ortiz ◽  
Georgina P Blasco ◽  
Daniel I Brooks
Keyword(s):  
Medical Treatment ◽  
Outcome Measures ◽  
Primary Outcome ◽  
Secondary Outcome ◽  
Published Data ◽  
Treatment Facility ◽  
Coping Ability ◽  
Medical Treatment Facility ◽  
Treatment Facilities ◽  
Skills Education

Abstract Introduction The number-one service-connected disability is tinnitus. Tinnitus currently has no cure, but the functional impact of tinnitus has been shown to be mitigated by Progressive Tinnitus Management (PTM), a multi-level management approach. The duration of PTM Level 3 skills education (PTM-SE) and the inclusion of mental health providers have been identified as barriers to implementation of PTM-SE in Department of Defense (DOD) medical treatment facilities. The goal of this study was to determine if a version of PTM-SE modified for use in DOD medical treatment facilities resulted in positive changes in tinnitus-related outcomes. Materials and Methods A retrospective study was conducted by examining the medical records of patients who attended modified PTM-SE appointments. The study was approved by the Walter Reed National Military Medical Center Institutional Review Board. The study sample included 130 patients who completed modified PTM-SE between January 2015 and June 2016. Primary outcome measures were tinnitus awareness and tinnitus annoyance; secondary outcome measures were effect on life and self-perceived coping ability. Outcome measures were analyzed with nonparametric statistics and logistic regression. Results Modified PTM-SE resulted in clinically significant improvements in the primary outcome measures (awareness, p &lt; 0.0001; annoyance, p &lt; 0.0001). The proportion of patients who indicated an improvement in coping with tinnitus was similar to other published data with similar modifications to PTM-SE. Conclusions The evidence supports the assumption that PTM is a flexible program of tinnitus management that even when modified to be suitable for use in a DOD medical treatment facility provides meaningful reductions in tinnitus awareness and annoyance and improves tinnitus coping ability among military beneficiaries. These findings should encourage audiologists to modify PTM to work within their military medical treatment facility.

Treatment switch in Fabry disease- a matter of dose?

2020 ◽  
pp. jmedgenet-2020-106874
Author(s):  
Malte Lenders ◽  
Peter Nordbeck ◽  
Sima Canaan-Kühl ◽  
Lukas Kreul ◽  
Thomas Duning ◽  
...  
Keyword(s):  
Fabry Disease ◽  
Dose Group ◽  
Clinical Symptoms ◽  
Organ Damage ◽  
Agalsidase Beta ◽  
Disease Epidemiology ◽  
Reduced Dose ◽  
Clinical Events ◽  
Agalsidase Alfa ◽  
Switch Group

BackgroundPatients with Fabry disease (FD) on reduced dose of agalsidase-beta or after switch to agalsidase-alfa show a decline in chronic kidney disease epidemiology collaboration-based estimated glomerular filtration rate (eGFR) and a worsened plasma lyso-Gb3 decrease. Hence, the most effective dose is still a matter of debate.MethodsIn this prospective observational study, we assessed end-organ damage and clinical symptoms in 78 patients who had received agalsidase-beta (1.0 mg/kg) for >1 year, which were assigned to continue this treatment (agalsidase-beta, regular-dose group, n=17); received a reduced dose of agalsidase-beta and subsequent switch to agalsidase-alfa (0.2 mg/kg) or a direct switch to 0.2 mg/kg agalsidase-alfa (switch group, n=22); or were re-switched to agalsidase-beta after receiving agalsidase-alfa for 12 months (re-switch group, n=39) with a follow-up of 88±25 months.ResultsNo differences for clinical events were observed for all groups. Patients within the re-switch group started with the worst eGFR values at baseline (p=0.0217). Overall, eGFR values remained stable in the regular-dose group (p=0.1052) and decreased significantly in the re-switch and switch groups (p<0.0001 and p=0.0052, respectively). However, in all groups males presented with an annual loss of eGFR by –2.9, –2.5 and −3.9 mL/min/1.73 m² (regular-dose, re-switch, switch groups, all p<0.05). In females, eGFR decreased significantly only in the re-switch group by −2.9 mL/min/1.73 m² per year (p<0.01). Lyso-Gb3 decreased in the re-switch group after a change back to agalsidase-beta (p<0.05).ConclusionsOur data suggest that a re-switch to high dosage of agalsidase results in a better biochemical response, but not in a significant renal amelioration especially in classical males.

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