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Was ist 3

was ist 3

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Bei uns findet ihr auch die Bedeutung der Snapchat-Smileys. Darum verwende ich hier mal ein Bild… zur Erklärung eines Bildes. Kommentare zu diesem Artikel. Einzahlung in die Säule 3a Ironie, Sarkasmus, aber auch Angst, Überraschung und andere Gefühle können über lose Worte nicht ausgedrückt werden. Diese Beiträge können in beliebiger Höhe einbezahlt werden. Also der Inbegriff von niedlich.

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The system would not accept patients with blood pressure or glucose levels outside protocol-defined criteria appendix pp 4—5 or other data inconsistencies.

The system used a minimisation algorithm to achieve optimum balance for key prognostic factors table 1 , and from January, , minimisation was additionally stratified by world region and then minimised on all the other key factors within regions.

Percentages exclude missing values from denominators. To be eligible to join the trial, participating hospitals had to have an organised system of stroke care.

Acute-care protocols were not specified by the trial, but had to include the components of effective stroke-unit care, 19 including, soon after admission, intravenous access, monitoring of physiological variables, correction of any abnormalities, and where clinically appropriate, intravenous-fluid therapy.

All patients in the trial were to be treated within that organised system of stroke care, irrespective of treatment allocation.

Patients allocated to the control group were to avoid treatment with rt-PA and received stroke care in the same clinical environment as those allocated to the rt-PA group.

Both treatment groups had blood pressure monitored closely over the first 24 h. In the double-blinded phase, both groups were to avoid antiplatelet or anticoagulant therapy for 24 h.

In the open phase, patients allocated to the control group were to start aspirin immediately. Blood pressure was managed in the same way in both treatment groups, according to local protocol.

Additionally, all centres were asked for their pretrial experience of thrombolysis for treatment of stroke, and if the centre had, before joining the trial, a protocol for open-label use of rt-PA and had treated at least three people in the 12 months before joining the trial, the centre was classed as experienced.

A repeat brain scan was required if the patient deteriorated neurologically or intracranial haemorrhage was suspected for any reason.

All scans were sent to the trial centre in Edinburgh for masked central rating of any signs of visible early ischaemia presence and extent of hypo-attenuation, swelling, hyperattenuated artery , haemorrhage, and background brain changes leukoaraiosis, atrophy, prior stroke lesions, non-stroke lesions with validated rating methods.

All assessments were made masked to all patient details and treatment allocation. The statistical analysis plan specified an ordinal analysis of the OHS score at 6 months.

Additional secondary outcomes were to be reported separately. Events occurring within 7 days of stroke were recorded by the local trial clinician on the 7-day form: Other fatal and non-fatal non-cerebral events were also recorded and coded.

Data on potential reports of any of these events were extracted from the trial database and presented to the adjudication committee who were masked to treatment allocation.

Additional details of the procedures used in the double-blinded phase of the study are reported elsewhere. With the exception of the patients treated in the double-blinded phase of the trial, treatment was given openly and neither the patient nor the treating clinicians were masked.

Hospital staff completed an early outcome form at 7 days, death, or hospital discharge, whichever occured first, recording details of events occurring in hospital within 7 days, details of background treatments given and functional status.

If appropriate, the IST-3 trial office masked staff then mailed a postal questionnaire to patients to assess outcome. Non-responders were contacted by telephone, and follow-up data was obtained by telephone interview.

In Italy and Austria, all follow-ups were done as telephone interviews by a clinician, who was masked to treatment allocation and was highly experienced in outcome assessment.

In Portugal, patients were followed up in clinic by clinicians not involved in the patients' initial treatment, again, masked to treatment allocation as far as possible.

To assess the durability of any treatment benefit beyond 6 months, patients recruited in the UK and in other countries where appropriate funding had been obtained were also followed up at 18 months.

All follow-up done by patient contact for these analyses ceased on March 31, , but recording of deaths from national registries of deaths continues in UK, Norway, and Sweden.

However, it was clear by that obtaining a sample of was no longer feasible, and the Steering Committee agreed a revised recruitment target.

All IST-3 monitoring procedures were compliant with requirements of all study sponsors, the national ethics committees and regulatory agencies in the 12 participating countries, and they met all appropriate regulatory and Good Clinical Practice requirements.

All baseline data, 7-day, and 6-month outcome data were subject to verification checks built into the randomisation and data management system.

We monitored all baseline and postrandomisation imaging, which provided additional cross-checks on recruited patients and centre performance. An expert radiologist checked all scans, masked to clinical details and treatment allocation, immediately on receipt at the trial office, for evidence of adverse events and protocol deviations.

The independent data monitoring committee met at least annually to review the unmasked data on major outcome events in the trial, on the background stroke-unit care received by trial patients to ensure it was equal in both treatment groups , relevant external data including updates of the Cochrane systematic review and reports from large-scale registries of rt-PA use in strict confidence throughout the course of the trial.

The committee judged these data never met the protocol-specified criteria to recommend modification of the protocol or halt recruitment to the study.

The statistical analysis plan was published 14 before unmasking of the authors to the data. All randomly assigned patients were included in the analysis.

Masked analysis of the patients' baseline characteristics showed clear differences in key prognostic factors age, stroke severity, degree of ischaemic change on baseline CT or MRI in patients randomly assigned at different times after stroke onset, which might complicate the estimation of the effect of treatment overall and in subgroups.

An unadjusted analysis is also presented. The statistical-analysis-plan writing committee, which did not have access to the accumulating data, was therefore expanded to include an independent statistician Gordon Murray, University of Edinburgh, Edinburgh, UK to advise on the correct approach.

The writing group was persuaded by the recent empirical evidence that the ordinal method was both statistically more efficient effectively reducing the sample size required in stroke trials 29 and robust against substantial deviations from the proportional assumption.

In this model the treatment odds ratios between one level and the next were assumed to be constant, so a single parameter summarises the shift in outcome distribution between treatment and control groups.

For patients known to be alive at 6 months, but with an unknown OHS, we used the level of function recorded on the 7-day form ie, measured at 7 days or before discharge from hospital to impute 6-month functional status.

Analyses were done with SAS version 9. The sponsors of the study had no role in design, data collection, data analysis, data interpretation, or writing of the report.

The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication.

Between May, , and July, , patients were enrolled in centres in 12 countries. Baseline characteristics were well balanced between treatment groups figure 1 , table 1.

Additional baseline characteristics are shown in appendix pp 2—3. Appendix pp 4—5 gives more detail of treatment actually received and background care.

Appendix pp 2—3 documents deviations from the protocol and the background treatments that were given during the first 7 days.

Most patients were cared for in a stroke unit, and there was no evidence of a major imbalance in the use of background treatments or place of care admissions ward, or stroke unit over the first 7 days; an analysis of blood pressure in patients measured after randomisation showed no significant difference at each timepoint over the first 24 h in either systolic or diastolic blood pressures between the two treatment groups.

More patients died within 7 days in the rt-PA group than in the control group, but between 7 days and 6 months there were correspondingly fewer deaths in the rt-PA group.

For the ordinal analysis, which was adjusted for age, National Institutes of Health Stroke Scale NIHSS , delay all linear , and and presence or absence of visible acute ischaemic change on baseline scan as judged by the expert reader, the statistical analysis plan prespecified that OHS levels 4, 5, and 6 were grouped and 0, 1, 2, 3 remained discrete.

Estimated group difference for primary and secondary outcomes at 3 months, 8 months, and 12 months, based on intention-to-treat analysis.

Symptomatic intracranial haemorrhage and fatal or non-fatal deterioration due to swelling of the infarct within 7 days occurred in more patients in the rt-PA group than in the control group table 3.

To assess the effect of treatment on the primary outcome, the statistical analysis plan predefined a small subset of key prognostic subgroups figure 3.

The subgroup analyses are of the adjusted effects and take account of the fact that, for a specific prognostic factor, the distribution of other factors might differ between subcategories.

For example, in older patients the time to randomisation was shorter. The subgroup analyses for a specific factor provide estimated effects within sub-categories that adjust for such imbalances.

Overall, little variation occurred in the adjusted effects of treatment in different subgroups. Significant trends towards larger effects of treatment in more severe strokes were also seen as assessed by the NIHSS and by the predicted probability of a poor outcome Benefit was greatest in patients treated within 3 h, but there was insufficient power to examine decay of benefit with time.

An analysis of the treatment effect in each of three equal-sized cohorts of patients ie, those recruited in —06, —08, —11 did not provide any evidence of period effects data not shown.

Adjusted effect of treatment on the primary outcome alive and independent, Oxford Handicap Score 0, 1, or 2 in subgroups. The treatment odds ratio in each subgroup has been adjusted for the linear effects of the other key variables age, NIHSS, and delay but not for the presence or absence visible ischaemic change.

The choice of cut-points to define certain subgroups is slightly different to those given in table 1. The graph was generated with R version 2.

Although the increase in the number of patients treated with rt-PA who were alive and independent at 6 months was smaller than originally anticipated and was not significant, the secondary analysis provides supportive evidence of benefit.

The ordinal analysis provided evidence that on average, patients treated with intravenous thrombolysis up to 6 h after stroke survived with less disability.

At 6 months, vital status was known for most patients and there was no evidence of any difference in the number of deaths, despite the excess of deaths within 7 days of stroke mainly due to intracranial haemorrhage.

Since mortality at 6 months was equal in the two groups, and in view of the evidence that the lower the patients' degree of disability at 6 months, the greater their subsequent survival, 31 long-term follow-up beyond 6 months is important.

Follow-up for survival, therefore, continues in the UK, Norway, and Sweden to assess whether an overall survival advantage from rt-PA after 6 months emerges.

Was ist ein Söldengut. The following other wikis use this file: Was ist ein Söldengut Seite: Retrieved from " https: Journal von und für Franken.

Views View Edit History. This page was last edited on 1 November , at By using this site, you agree to the Terms of Use and Privacy Policy. The binary system that they suggested involved a return to British—era time zones; the recommendations were not adopted.

In , the government established a four—member committee under the Ministry of Science and Technology to examine the need for multiple time zones and daylight saving.

Though the government has consistently refused to split the country into multiple time zones, provisions in labour laws such as the Plantations Labour Act, allow the Central and State governments to define and set the local time for a particular industrial area.

The filmmaker Jahnu Barua has been campaigning for a separate time zone daylight saving time for the past 25 years.

In , he suggested creating a separate time zone for the Development of Northeastern Region. Official time signals are generated by the Time and Frequency Standards Laboratory at the National Physical Laboratory in New Delhi, for both commercial and official use.

The signals are based on atomic clocks and are synchronised with the worldwide system of clocks that support the Coordinated Universal Time.

IST is taken as the standard time as it passes through almost the centre of India. To communicate the exact time to the people, the exact time is broadcast over the national All India Radio and Doordarshan television network.

Telephone companies have dedicated phone numbers connected to mirror time servers that also relay the precise time.

From Wikipedia, the free encyclopedia. Archived from the original on 9 May

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