scholarly journals How to Establish the Outer Limits of Reperfusion Therapy

Stroke ◽  
2021 ◽  
Author(s):  
Lawrence R. Wechsler ◽  
Ashutosh P. Jadhav ◽  
Tudor G. Jovin ◽  
Opeolu Adeoye ◽  
Greg Albers ◽  
...  
Keyword(s):  
Treatment Effects ◽  
Statistical Significance ◽  
Minimum Clinically Important Difference ◽  
Reperfusion Therapy ◽  
Medical Community ◽  
Imaging Features ◽  
Significant Treatment ◽  
Stroke Treatment ◽  
Clinically Significant ◽  
Alternative Sources

Reperfusion therapy with intravenous alteplase and endovascular therapy are effective treatments for selected patients with acute ischemic stroke. Guidelines for treatment are based upon randomized trials demonstrating substantial treatment effects for highly selected patients based on time from stroke onset and imaging features. However, patients beyond the current established guidelines might benefit with lesser but still clinically significant treatment effects. The STAIR (Stroke Treatment Academic Industry Roundtable) XI meeting convened a workgroup to consider the “outer limits” of reperfusion therapy by defining the current boundaries, and exploring optimal parameters and methodology for determining the outer limits. In addition to statistical significance, the minimum clinically important difference should be considered in exploring the limits of reperfusion therapy. Societal factors and quality of life considerations should be incorporated into assessment of treatment efficacy. The threshold for perception of benefit in the medical community may differ from that necessary for the Food and Drug Administration approval. Data from alternative sources such as platform trials, registries and large pragmatic trials should supplement randomized controlled trials to improve generalizability to routine clinical practice. Further interactions between industry and academic centers should be encouraged.

scholarly journals Acute effects of mustard, horseradish, black pepper and ginger on energy expenditure, appetite,ad libitumenergy intake and energy balance in human subjects

2012 ◽  
Vol 109 (3) ◽  
pp. 556-563 ◽  
Author(s):  
N. T. Gregersen ◽  
A. Belza ◽  
M. G. Jensen ◽  
C. Ritz ◽  
C. Bitz ◽  
...  
Keyword(s):  
Energy Balance ◽  
Treatment Effects ◽  
Human Subjects ◽  
Statistical Significance ◽  
Black Pepper ◽  
Normal Weight ◽  
Acute Effects ◽  
Significant Treatment ◽  
Ad Libitum ◽  
Few Data

Chilli peppers have been shown to enhance diet-induced thermogenesis (DIT) and reduce energy intake (EI) in some studies, but there are few data on other pungent spices. The primary aim of the present study was to test the acute effects of black pepper (pepper), ginger, horseradish and mustard in a meal on 4 h postprandial DIT. The secondary aim was to examine the effects on subjective appetite measures,ad libitumEI and energy balance. In a five-way placebo-controlled, single-blind, cross-over trial, twenty-two young (age 24·9 (sd4·6) years), normal-weight (BMI 21·8 (sd2·1) kg/m2) males were randomly assigned to receive a brunch meal with either pepper (1·3 g), ginger (20 g), horseradish (8·3 g), mustard (21 g) or no spices (placebo). The amounts of spices were chosen from pre-testing to make the meal spicy but palatable. No significant treatment effects were observed on DIT, but mustard produced DIT, which tended to be larger than that of placebo (14 %, 59 (se3)v.52 (se2) kJ/h, respectively,P= 0·08). No other spice induced thermogenic effects approaching statistical significance. Subjective measures of appetite (P>0·85),ad libitumEI (P= 0·63) and energy balance (P= 0·67) also did not differ between the treatments. Finally, horseradish decreased heart rate (P= 0·048) and increased diastolic blood pressure (P= 0·049) compared with placebo. In conclusion, no reliable treatment effects on appetite, EI or energy balance were observed, although mustard tended to be thermogenic at this dose. Further studies should explore the possible strength and mechanisms of the potential thermogenic effect of mustard actives, and potential enhancement by, for example, combinations with other food components.

scholarly journals Removing the Mask of Average Treatment Effects in Chronic Lyme Disease Research Using Big Data and Subgroup Analysis

Healthcare ◽  
2018 ◽  
Vol 6 (4) ◽  
pp. 124 ◽  
Author(s):  
Lorraine Johnson ◽  
Mira Shapiro ◽  
Jennifer Mankoff
Keyword(s):  
Lyme Disease ◽  
Treatment Effects ◽  
Group Analysis ◽  
Treatment Protocol ◽  
Medical Community ◽  
Patient Registries ◽  
Average Treatment ◽  
Individualized Care ◽  
Patient Reported ◽  
Average Treatment Effects

Lyme disease is caused by the bacteria borrelia burgdorferi and is spread primarily through the bite of a tick. There is considerable uncertainty in the medical community regarding the best approach to treating patients with Lyme disease who do not respond fully to short-term antibiotic therapy. These patients have persistent Lyme disease symptoms resulting from lack of treatment, under-treatment, or lack of response to their antibiotic treatment protocol. In the past, treatment trials have used small restrictive samples and relied on average treatment effects as their measure of success and produced conflicting results. To provide individualized care, clinicians need information that reflects their patient population. Today, we have the ability to analyze large data bases, including patient registries, that reflect the broader range of patients more typically seen in clinical practice. This allows us to examine treatment variation within the sample and identify groups of patients that are most responsive to treatment. Using patient-reported outcome data from the MyLymeData online patient registry, we show that sub-group analysis techniques can unmask valuable information that is hidden if averages alone are used. In our analysis, this approach revealed treatment effectiveness for up to a third of patients with Lyme disease. This study is important because it can help open the door to more individualized patient care using patient-centered outcomes and real-world evidence.

scholarly journals A Reappraisal of Rhythmic Coma Patterns in Children

2005 ◽  
Vol 32 (4) ◽  
pp. 518-523 ◽  
Author(s):  
Rajesh RamachandranNair ◽  
Rohit Sharma ◽  
Shelly K. Weiss ◽  
Hiroshi Otsubo ◽  
Miguel A. Cortez
Keyword(s):  
Statistical Significance ◽  
Prognostic Significance ◽  
Favourable Outcome ◽  
Category Scale ◽  
Rhythmic Pattern ◽  
Performance Category ◽  
Exact Test ◽  
Significant Difference ◽  
Overall Performance ◽  
Clinically Significant

ABSTRACT:Objective:This study was designed to determine the prevalence of rhythmic coma patterns in comatose children and to ascertain the prognostic significance of reactive rhythmic coma patterns.Methods:We retrospectively analyzed and classified electroencephalogram (EEGs) in comatose children between two months and 18 years of age during the period 1996 - 2003 according to modified Young's classification. Outcome at one-year was scored according to the Paediatric Cerebral and Overall Performance Category Scale. Outcomes were compared using Fisher's exact test and Mann-Whitney test.Results:Analysis of 63 electroencephalogram (EEG) records in 38 patients showed rhythmic patterns in 19 records (30.2%; 9 alpha, 4 spindle, 4 theta and 2 beta coma patterns, total number of children = 14). Aetiology and outcome of alpha coma patterns and other rhythmic coma patterns were similar. In five children, one type of rhythmic pattern changed to another. Records with reactive rhythmic coma 66.7% (6/9), were associated with favourable outcome. Sixty percent of the records (6/10 records in seven children) with non-reactive pattern were associated with unfavourable outcome. This clinically significant difference did not reach statistical significance (lower Paediatric Cerebral and Overall Performance Category Scale score p= 0.14; favourable outcome p=0.19).Conclusion:Rhythmic coma patterns in comatose children are not uncommon. Aetiology, reactivity and outcome of individual patterns are similar and thus make the rhythmic coma patterns distinct EEG signatures in comatose children. There was a clinically significant better outcome with reactive rhythmic coma patterns.

Abstract WMP17: Early DWI Reversal Following Endovascular Reperfusion Is Typically Transient

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Manabu Inoue ◽  
Hayley M Wheeler ◽  
Michael Mlynash ◽  
Aaryani Tipirneni ◽  
Matus Straka ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Endovascular Therapy ◽  
Independent Predictor ◽  
Infarct Volume ◽  
Prognostic Significance ◽  
Reperfusion Therapy ◽  
Ischemic Lesion ◽  
Stroke Treatment ◽  
Median Volume

Background and Purpose: There are conflicting reports regarding the incidence and prognostic significance of DWI reversal following reperfusion therapy. The aim of this study was to assess the frequency and extent of early DWI reversal following endovascular therapy and to determine if early reversal is sustained or transient. Methods: This is a substudy of the DEFUSE 2. MRI with DWI and PWI was performed before (DWI 1) and within 12 hours after (DWI 2) endovascular stroke treatment and again at 5 days. Acute DWI lesions were outlined and quantified using mipav software (http://mipav.cit.nih.gov/). Ischemic lesion volumes were outlined on the Day 5 FLAIR then corrected for edema using a validated technique to determine the final infarct volume. Early DWI reversal was defined as (DWI 1 - DWI 2) >3 ml and permanent DWI reversal was defined (DWI 1 - final infarct volume) > 1 ml. Reperfusion was defined as a >50% reduction in PWI volume (Tmax >6 sec) on the MRI performed after endovascular therapy. The prognostic significance of early reversal was assessed in a regression model. Results: 104 patients had a technically adequate DWI and PWI prior to endovascular therapy (performed 4.4 [3.0-6.0] hours after symptom onset). Of these, 77 had an acute DWI lesion >3 ml and a follow-up MRI (156 min [72-342] after completion of endovascular therapy) and a 5 day MRI. Seventeen percent (13/77) of the patients had early DWI reversal representing a median (IQR) of 42.4% (25.0-57.6) of the initial DWI lesion (median volume 10.9 ml [IQR 7.3-18.2]). The incidence of early DWI reversal was 21% (11/52) following reperfusion vs. 8% (2/25) in patients who did not reperfuse (p=0.20). Of the 13 patients with early DWI reversal, permanent DWI reversal occurred in only 2 (volume of permanent DWI reversal 6.9 ml and 4.7 ml). Early DWI reversal was not an independent predictor of clinical outcome. Conclusion: Early DWI reversal occurs in about 15-20% of patients following endovascular therapy and can involve a substantial percentage of the initial DWI volume. However, early DWI reversal is usually transient and does not appear to signify tissue salvage.

Abstract WP22: Reperfusion Therapy After Neurological Deterioration in Acute Ischemic Stroke

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Mooseok Park ◽  
Tai Hwan Park ◽  
Sang-Soon Park ◽  
Jong-Moo Park ◽  
Yong-Jin Cho ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Clinical Features ◽  
Statistical Significance ◽  
Multivariable Analysis ◽  
Reperfusion Therapy ◽  
Neurological Deterioration ◽  
Large Artery ◽  
Good Outcome ◽  
Intravenous Tissue Plasminogen Activator

Background: Guidelines do not recommend reperfusion therapy in acute ischemic stroke patients with mild symptoms considering low gain compared to the risk. However, some patients with mild first symptoms experience neurological deterioration (ND) after hospitalization. We aimed to analyze clinical features and outcomes of patient who received reperfusion therapy after ND occurred. Methods: We enrolled patients who were admitted within 7 days after acute ischemic stroke or TIA between January 2012 and July 2018 from a multicenter stroke registry database in Korea (CRCS-K). Patients who 1) admitted via emergency room, and 2) received reperfusion therapy including intravenous tissue plasminogen activator and/or endovascular treatment were included. Clinical features and outcomes such as modified Rankin Scale (mRS) score distribution at 3 months after stroke were compared between patients received reperfusion therapy after ND and those without ND before the treatment. Results: Among 51325 patients, 6577 (12.8%) received reperfusion therapy were identified. Reperfusion therapy was performed after ND in 136 patients (2.1%). Mean time of onset to needle is 342.1 and 167.2, and onset to perfusion is 1351.6 and 422.0 in patients treated after ND, and those without, respectively. TIA history was more frequent and atrial fibrillation history was less frequent in patients treated after ND. Initial median (IQR) National Institute of Health Stroke Scale (NIHSS) score was 8 (5 - 12), 10 (6 - 16) in patients treated after ND, and those without, respectively. Large artery atherosclerosis was more frequent in patients treated after ND (42.9 % vs. 26.7%). There was higher rate of good outcome at 90 days in patients treated after ND (84 [61.8%]) compared with those without ND before treatment (3359 [52.2%]; OR, 1.38 [95% CI, 1.02-1.87]). In multivariable analysis, good outcome at 90 days in patients treated after ND lacked statistical significance (OR, 1.06 [95% CI, 0.71-1.62]). There is no significant statistical difference of death at 90 days (13.2% vs. 10.4%, p = 0.364). Conclusion: Reperfusion therapy could apply patients with mild first symptoms experience ND after hospitalization and expect similar prognosis compared to those without ND before the treatment.

A PSA for Radiologists: Pictorial Review of Incidentalomas on Prostate Magnetic Resonance Imaging

2019 ◽  
Vol 70 (2) ◽  
pp. 134-146 ◽  
Author(s):  
Amanzo A. Ho ◽  
S. Sejal Khara ◽  
David J. Ferguson ◽  
Mohammed F. Mohammed ◽  
Silvia D. Chang ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Magnetic Resonance ◽  
Incidental Findings ◽  
Imaging Study ◽  
Imaging Features ◽  
Resonance Imaging ◽  
Patient Anxiety ◽  
Prostate Mri ◽  
Pictorial Review ◽  
Clinically Significant

Multiparametric magnetic resonance imaging (MRI) of the prostate is a powerful and increasingly utilized imaging study for the diagnosis, staging, and surveillance of prostate cancer. With greater adoption by clinicians, it is becoming more common for incidental findings to be first detected on prostate MRI. Inadequate description of clinically significant findings may not prompt appropriate patient management, while over-reporting of indolent findings comes at increased patient anxiety, cost of workup, and iatrogenic risk. This review article aims to improve awareness, review pathophysiology, and present key imaging features of incidental findings seen on prostate MRI, ranging from common to rare and from benign to clinically significant.

Sterility and performance of open and closed extracorporeal circuits after long-term dry-wet setups

Perfusion ◽  
2020 ◽  
pp. 026765912093789
Author(s):  
Joseph Deptula ◽  
Catrina McGrath ◽  
Thomas Preston ◽  
Hayden Miller ◽  
Bianca Yen ◽  
...  
Keyword(s):  
Lactate Dehydrogenase ◽  
Statistical Significance ◽  
Blood Gases ◽  
Free Hemoglobin ◽  
Randomized Clinical Study ◽  
Minute Post ◽  
Extracorporeal Circuits ◽  
Clinically Significant ◽  
Run Up ◽  
And Performance

Background: The timeframe for safely using previously setup dry, crystalloid, and blood-primed extracorporeal circuits has long been debated. This study was undertaken to determine a safe deviation from standardized recommendations. Methods: Open (cardiopulmonary bypass) circuits and closed extracorporeal membrane oxygenation circuits were setup dry for up to 60 days and wet primed for up to 6 weeks with one control inoculated with Escherichia coli. Open circuits were cultured daily, closed circuits weekly. Circuits were primed with blood, albumin, heparin, NaHCO3, and CaCl2. Baseline pCO2, pO2, hemoglobin, lactate dehydrogenase, and plasma free hemoglobin were measured. Circuits were recirculated at a blood flow of 6 Liters/minute with a sweep gas of 1 Liter/minute at 100% FiO2 for 1 minute. Post oxygenator blood gases were collected at 8-, 16-, and 24-hour intervals. Results: There was no observed compromise to the sterility of the circuits and no clinically significant gas exchange abnormalities observed over the duration of the study period. Statistical significance (p < 0.01) was seen in free hemoglobin and lactate dehydrogenase levels, most significant in between the 16- and 24-hour time point in the closed systems intentionally inoculated with E. coli. Conclusion: Open and closed circuits can be safely setup dry for up to 60 days. Open, wet-primed circuits can be used safely up to 5 days. Closed, wet-primed circuits can be used safely up to 6 weeks. Blood-primed circuits can be safely run up to 16 hours prior to patient use but should be validated in a randomized clinical study.

scholarly journals Unravelling the mystery of the ‘minimum important difference’ using practical outcome measures in chronic respiratory disease

2019 ◽  
Vol 16 ◽  
pp. 147997311881649 ◽  
Author(s):  
Linzy Houchen-Wolloff ◽  
Rachael A Evans
Keyword(s):  
Outcome Measures ◽  
Outcome Measure ◽  
Statistical Significance ◽  
Minimum Clinically Important Difference ◽  
Chronic Respiratory Disease ◽  
Important Change ◽  
P Value ◽  
Minimum Important Difference ◽  
The Mean ◽  
Functional Outcome Measures

It is important for clinicians and researchers to understand the effects of treatments on their patients, both at an individual and group level. In clinical studies, treatment effects are often reported as a change in the outcome measure supported by a measure of variability; for example, the mean change with 95% confidence intervals and a probability ( p) value to indicate the level of statistical significance. However, a statistically significant change may not indicate a clinically meaningful or important change for clinicians or patients to interpret. The minimum clinically important difference (MCID) or minimally important difference (MID) has therefore been developed to add clinical relevance or patient experience to the reporting of an outcome measure. In this article, we consider the concept of the MID using the example of practical outcome measures in patients with CRD. We describe the various ways in which an MID can be calculated via anchor- and distribution-based methods, looking at practical examples and considering the importance of understanding how an MID was derived when seeking to apply it to a particular situation. The terms MID and MCID are challenging and often used interchangeably. However, we propose all MIDs are described as such, but they could be qualified by a suffix: MIDS (MID – Statistical), MID-C (MID – Clinical outcome), MID-P (MID – Patient determined). However, this type of classification would only work if accepted and adopted. In the meantime, we advise clinicians and researchers to use an MID where possible to aid their interpretation of functional outcome measures and effects of interventions, to add meaning above statistical significance alone.

scholarly journals Preventative, but not post-stroke, inhibition of CD36 attenuates brain swelling in hyperlipidemic stroke

2019 ◽  
Vol 40 (4) ◽  
pp. 885-894 ◽  
Author(s):  
Eunhee Kim ◽  
Jiwon Yang ◽  
Keun Woo Park ◽  
Sunghee Cho
Keyword(s):  
Therapeutic Strategy ◽  
Infarct Volume ◽  
Statistical Significance ◽  
Preventative Treatment ◽  
Brain Swelling ◽  
Pharmacological Interventions ◽  
Stroke Treatment ◽  
Post Stroke ◽  
Treatment Paradigm ◽  
Potential Benefits

The lack of inclusion of comorbidities in animal models of stroke may underlie the limited development of therapy in stroke. Previous studies in mice deficient of CD36, an immune receptor, indicated its contribution to stroke-induced inflammation and injury in hyperlipidemic conditions. The current study, therefore, tested whether pharmacological inhibition of CD36 provides neuroprotection in hyperlipidemic stroke. The hyperlipidemic mice subjected to stroke showed an exacerbation of infarct size and profound brain swelling. However, post-stroke treatment with CD36 inhibitors did not reduce, and in some cases worsened, acute stroke outcome, suggesting potential benefits of elevated CD36 in the post-stroke brain in a hyperlipidemic condition. On the other hand, chronic treatment of a CD36 inhibitor prior to stroke significantly reduced stroke-induced brain swelling. There was a trend toward infarct reduction, although it did not reach statistical significance. The observed benefit of preventative CD36 inhibition is in line with previously reported smaller infarct volume and swelling in CD36 KO mice. Thus, the current findings suggest that insights gained from the genetic models should be carefully considered before the implementation of pharmacological interventions, as a potential therapeutic strategy may depend on preventative treatment or a post-stroke acute treatment paradigm.

scholarly journals Impact of season and geography on CompEx Asthma: a composite end-point for exacerbations

2020 ◽  
Vol 6 (4) ◽  
pp. 00246-2020
Author(s):  
Alexandra Jauhiainen ◽  
Lieke E.J.M. Scheepers ◽  
Anne L. Fuhlbrigge ◽  
Tim Harrison ◽  
James Zangrilli ◽  
...  
Keyword(s):  
Eastern Europe ◽  
Randomised Controlled Trials ◽  
Treatment Effects ◽  
Statistical Significance ◽  
Fold Increase ◽  
Controlled Trials ◽  
End Point ◽  
Geographical Regions ◽  
Randomised Controlled ◽  
Event Rates

BackgroundCompEx Asthma, a novel composite end-point combining severe exacerbations (SevEx) with asthma-worsening events, was recently developed. Further characterisation of CompEx Asthma is needed to illustrate the applicability of this end-point. The objective was to evaluate CompEx Asthma as a rate end-point to determine how seasonal and geographical factors impact this novel outcome.MethodsSeven 24–56-week randomised controlled trials of budesonide/formoterol (BUD/FORM) and benralizumab were analysed. Annualised event rates (AERs) and treatment effects (hazard ratio (HR)) were analysed with Poisson and Andersen–Gill models, respectively. Seasonality was analysed by month and five geographical regions were evaluated.ResultsThe studies included 10 815 patients (63% female, mean age 42–49 years). CompEx Asthma AER mirrored seasonal variations in SevEx AER. CompEx Asthma AERs were higher versus SevEx in BUD/FORM and benralizumab trials (range 2.7–4.5-fold and 1.3–2.0-fold increase, respectively) and were less variable versus SevEx between regions (ratios of greatest:smallest AERs: 1.36 for CompEx versus 2.28 for SevEx (BUD/FORM); 1.81 for CompEx versus 2.22 for SevEx (benralizumab)). Treatment effects for CompEx Asthma and SevEx were generally similar across regions and months. However, in Eastern Europe, where SevEx rates were lowest, treatment effect was greater with CompEx Asthma versus SevEx, reaching statistical significance in the benralizumab studies (HR (95% CI): 0.67 (0.53–0.85) versus 0.87 (0.65–1.15)).ConclusionThis study confirmed the reliability of CompEx Asthma as a rate end-point and allowed detection of variations in seasonal SevEx rates, reduction of variation in rates across regions and potential greater sensitivity to treatment effects.

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