External Validation of a Dynamic Prediction Model for Upper Limb Function After Stroke

Objective: To externally validate the dynamic prediction model for prediction of upper limb (UL) function 6 months after stroke. The dynamic prediction model has been developed and cross-validated on data from 4 Dutch studies. Design: Data from a prospective Danish cohort study were used to assess prediction accuracy. Setting: A Danish neurorehabilitation hospital. Participants: In this external validation study, follow-up data for 80 patients in the subacute phase after stroke (N=80), mean age 64 (SD11), 43% women, could be obtained. They were assessed at 2 weeks, 3 months, and 6 months after stroke with the Action Research Arm Test (ARAT), Fugl-Meyer Motor Assessment upper limb (FMA), and Shoulder Abduction (SA) Finger Extension (FE), (SAFE) test. Intervention: Not applicable. Main Outcome Measures: Prediction accuracy at 6 months was examined for 3 categories of ARAT (0-57 points): mild (48-57), moderate (23-47), and severe (0-22). Two individual predictions of ARAT scores at ±6 months post-stroke were computed based on, respectively, baseline (2 weeks) and 3 months ARAT, FE, SA values. The absolute individual differences between observed and predicted ARAT scores were summarized. Results: The prediction model performed best for patients with relatively good UL motor function, with an absolute error median (IQR) of 3 (2-9), and worst for patients with severe UL impairment, with a median (IQR) of 30 (3-39) at baseline. In general, prediction accuracy substantially improved when data obtained 3 months after stroke was included compared with baseline at 2 weeks after stroke. Conclusion: We found limited clinical usability due to the lack of prediction accuracy 2 weeks after stroke and for patients with severe UL impairments. The dynamic prediction model could probably be refined with data from biomarkers.</p

A statistical analysis protocol for the time-differentiated target temperature management after out-of-hospital cardiac arrest (TTH48) clinical trial

Background The TTH48 trial aims to determine whether prolonged duration (48 hours) of targeted temperature management (TTM) at 33 (±1) °C results in better neurological outcomes compared to standard duration (24 hours) after six months in comatose out-of-hospital cardiac arrest (OHCA) patients. Methods TTH48 is an investigator-initiated, multicentre, assessor-blinded, randomised, controlled superiority trial of 24 and 48 hours of TTM at 33 (±1) ° C performed in 355 comatose OHCA patients aged 18 to 80 years who were admitted to ten intensive care units (ICUs) in six Northern European countries. The primary outcome of the study is the Cerebral Performance Category (CPC) score observed at six months after cardiac arrest. CPC scores of 1 and 2 are defined as good neurological outcomes, and CPC scores of 3, 4 and 5 are defined as poor neurological outcomes. The secondary outcomes are as follows: mortality within six months after cardiac arrest, CPC at hospital discharge, Glasgow Coma Scale (GCS) score on day 4, length of stay in ICU and at hospital and the presence of any adverse events such as cerebral, circulatory, respiratory, gastrointestinal, renal, metabolic measures, infection or bleeding. With the planned sample size, we have 80% power to detect a 15% improvement in good neurological outcomes at a two-sided statistical significance level of 5%. Discussion We present a detailed statistical analysis protocol (SAP) that specifies how primary and secondary outcomes should be evaluated. We also predetermine covariates for adjusted analyses and pre-specify sub-groups for sensitivity analyses. This pre-planned SAP will reduce analysis bias and add validity to the findings of this trial on the effect of length of TTM on important clinical outcomes after cardiac arrest. Trial registration ClinicalTrials.gov: NCT01689077, 17 September 201

The Danish Atrial Fibrillation Registry:A Multidisciplinary National Pragmatic Initiative for Monitoring and Supporting Quality of Care Based on Data Retrieved from Administrative Registries

AIM: The Danish Atrial Fibrillation (AF) Registry monitors and supports improvement of quality of care for all AF patients in Denmark. This report describes the registry's administrative and organizational structure, data sources, data flow, data analyses, annual reporting, and feedback between the registry, clinicians, and the administrative system. We also report the selection process of the quality indicators and the temporal trends in results from 2017-2021.METHODS AND RESULTS: The Danish AF Registry aims for complete registration and monitoring of care for all patients diagnosed with AF in Denmark. Administrative registries provide data on contacts to general practice, contacts to private cardiology practice, hospital contacts, medication prescriptions, updated vital status information, and biochemical test results. The Danish Stroke Registry provides information on stroke events. From 2017 to 2021, the proportion with a reported echocardiography among incident AF patients increased from 39.9% (95% CI: 39.3-40.6) to 82.6% (95% CI: 82.1-83.1). The initiation of oral anticoagulant therapy among patients with incident AF and a CHA2DS2-VASc score of ≥1 in men and ≥2 in women increased from 85.3% (95% CI: 84.6-85.9) to 90.4% (95% CI: 89.9-91.0). The 1-year and 2-year persistence increased from 85.2% (95% CI: 84.5-85.9) to 88.7% (95% CI: 88.0-89.3), and from 85.4% (95% CI: 84.7-86.2) to 88.2% (95% CI: 87.5-88.8), respectively. The 1-year risk of ischemic stroke among prevalent patients with AF decreased from 0.88% (95% CI: 0.83-0.93) to 0.71% (95% CI: 0.66-0.75). Variation in clinical performance between the five administrative Danish regions was reduced.CONCLUSION: Continuous nationwide monitoring of quality indicators for AF originating from administrative registries is feasible and supportive of improvements of quality of care.</p

A statistical analysis protocol for the time-differentiated target temperature management after out-of-hospital cardiac arrest (TTH48) clinical trial

Background: The TTH48 trial aims to determine whether prolonged duration (48 hours) of targeted temperature management (TTM) at 33 (+/- 1) degrees C results in better neurological outcomes compared to standard duration (24 hours) after six months in comatose out-of-hospital cardiac arrest (OHCA) patients. Methods: TTH48 is an investigator-initiated, multicentre, assessor-blinded, randomised, controlled superiority trial of 24 and 48 hours of TTM at 33 (+/- 1) degrees C performed in 355 comatose OHCA patients aged 18 to 80 years who were admitted to ten intensive care units (ICUs) in six Northern European countries. The primary outcome of the study is the Cerebral Performance Category (CPC) score observed at six months after cardiac arrest. CPC scores of 1 and 2 are defined as good neurological outcomes, and CPC scores of 3, 4 and 5 are defined as poor neurological outcomes. The secondary outcomes are as follows: mortality within six months after cardiac arrest, CPC at hospital discharge, Glasgow Coma Scale (GCS) score on day 4, length of stay in ICU and at hospital and the presence of any adverse events such as cerebral, circulatory, respiratory, gastrointestinal, renal, metabolic measures, infection or bleeding. With the planned sample size, we have 80% power to detect a 15% improvement in good neurological outcomes at a two-sided statistical significance level of 5%. Discussion: We present a detailed statistical analysis protocol (SAP) that specifies how primary and secondary outcomes should be evaluated. We also predetermine covariates for adjusted analyses and pre-specify sub-groups for sensitivity analyses. This pre-planned SAP will reduce analysis bias and add validity to the findings of this trial on the effect of length of TTM on important clinical outcomes after cardiac arrest.Peer reviewe

How to Obtain Those Nasty Standard Errors From Transformed Data - and Why They Should Not Be Used

Introduction When statistical analyses are carried out, it is often neccessary to transform the measured value to make the assumptions used in the statistical analyses valid. When results are reported, the estimated values of e.g. treatment means are often transformed back to the measured or traditional scale. The advantage is that the results become readily comparable with results in similar studies. It has become accepted practice in many scientific journals to indicate the precision of such estimates by the estimated standard error of the estimate. For several reasons a more appropriate approach is to calculate the confidence interval of the estimate, e.g. it often includes the uncertainty in the estimate of the standard error. The argument for use of the standard error is, that it is more compact, i.e. only one value need to be reported, and if the estimates follow the normal distribution, confidence intervals can easily be calculated by means of the standard error. For e

The effects of inbreeding and heat stress on male sterility in Drosophila melanogaster

Understanding the consequences of inbreeding in combination with stress is important for the persistence of small endangered populations in a changing environment. Inbreeding and stress can influence the population at all stages of the life cycle, and in the last two decades a number of studies have demonstrated inbreeding depression for most life-cycle components, both in laboratory populations and in the wild. Although male fertility is known to be sensitive to temperature extremes, few studies have focused on this life-cycle component. We studied the effects of inbreeding on male sterility in benign and stressful environments using Drosophila melanogaster as a model organism. Male sterility was compared in 21 inbred lines and five non-inbred control lines at 25.0 and 29.0 degrees C. The effect of inbreeding on sterility was significant only at 29.0 C. This stress-induced increase in sterility indicates an interaction between the effects of inbreeding and high-temperature stress on male sterility. In addition, the stress-induced temporary and permanent sterility showed significant positive correlation, as did stress-induced sterility and the decrease in egg-to-adult viability. This suggests that the observed stress-induced decline in fitness could result from conditionally expressed, recessive deleterious alleles affecting both sterility and viability simultaneously. (C) 2011 The Linnean Society of London, Biological Journal of the Linnean Society, 2011, 104, 432-442

The Effects of High-Intensity Aerobic Exercise on Cognitive Performance After Stroke: A Pilot Randomised Controlled Trial

Background: Aerobic exercise is an effective treatment to improve aerobic capacity following stroke and might also improve cognitive impairments in sub-acute stroke survivors. The aim of the study was to assess the effect of high-intensity aerobic exercise on cognitive impairments in sub-acute stroke survivors. Methods: A pilot, randomised controlled trial on the effects of aerobic exercise on cognitive impairments of stroke patients in the sub-acute (1-3 months) phase was conducted. Thirty patients with moderate cognitive impairments (maximum score of 5 on at least two items on the cognitive subscales of the Functional Independence Measure [FIM]) were included in the study and randomly assigned to either the intervention group – performing high-intensity aerobic exercise (above 70% of maximum heart rate), or the control group – performing low-intensity aerobic exercise (below 60%). Patients in both groups exercised for 50 min twice a week for 4 weeks. Primary neuropsychological outcome: Trail Making Test B. Results: Thirty stroke patients completed the interventions. The results showed that the high-intensity group, compared with the low-intensity group, achieved significant improvements on Trail Making Test B, which assesses processing speed and divided attention ( P  = .04 after training and P  = .01 at follow-up). However, the significant improvements on Trail Making Test B might relate to a ceiling effect in the control group. Conclusions: This study does not provide evidence to support that aerobic exercise can improve cognition in stroke survivors, even though significant improvement was revealed on the primary outcome in sub-acute stroke survivors following high-intensity aerobic exercise compared with low-intensity general exercise