We wish to acknowledge all of the funding organizations, the &#34;Technology Foundation Berlin&#34; (TSB) via the &#34;Zukunftsfonds Berlin&#34;, the Federal Ministry of Education and Research via the grant CSB (01 EO 0801), the Volkswagen Foundation (Lichtenberg program to Matthias Endres), the EU (EuStroke, ARISE) and the German Research Foundation (NeuroCure, SFB-TR 43).

1. Emergency Response at the Dispatch Center of the Berlin Fire Brigade
<ol>
	<li>Answer an incoming &#34;112&#34; emergency call.</li>
	<li>Gather information about the emergency site, such as address, floor, name on the doorbell and phone number. Type the data directly into the worksheet of the computer-controlled emergency dispatch system (called Ignis)</li>
	<li>Identify the medical emergency as a stroke emergency, using the newly developed Dispatcher Identification Algorithm for Stroke Emergencies (DIASE).</li>
	<li>Verify that the emergency site is within the operating area of STEMO via Ignis.</li>
	<li>Communicate alarm to STEMO via a radio-based alarm system. (In Berlin, currently, a regular care ambulance is alarmed simultaneously.) Available information concerning the emergency is automatically transmitted via fax.</li>
</ol>
2. Receipt of the Alarm Transmission at the Fire Station
<ol>
	<li>A personal pager signals the alert by audible tone. Go immediately to the fax machine and take the fax containing the detailed emergency information.</li>
	<li>Go to the STEMO vehicle, press the status button 3 on the on-board radio, thus confirming a receipt for alert to the dispatch center. The GPS-based navigation system has automatically received a routing to the patient&#39;s location.</li>
	<li>When complete crew is on board (Paramedic, Neurologist and Radiology technician) drive the STEMO vehicle to the emergency site. CAUTION: Approach with blue lights flashing and siren to the scene. Therefore, pay particular attention to other road users and observe the regulations of the German traffic law concerning the use of blue lights and siren.</li>
	<li>Upon arrival at the emergency site, press the status button 4 on the on-board radio, thus giving a confirmation to the dispatch center.</li>
	<li>Pay extra attention to safety before leaving the STEMO vehicle at the emergency site. CAUTION: Watch out for potential hazards, such as unsecured scene of an accident, violent people, risk of fire, moving traffic or hazardous substances.</li>
</ol>
3. Examination of the Patient at the Emergency Site
<ol>
	<li>Check consciousness using the Glasgow Coma Scale (GCS).</li>
	<li>Follow the structured &#34;ABCDE algorithm&#34; for the initial assessment of the patient&#39;s status: Airways, Breathing, Circulation, Disability, Exposure13.</li>
	<li>Explore medical history of the patient. If stroke is suspected clinically assess severity of symptoms using the National Institutes of Health Stroke Scale (NIHSS).</li>
	<li>Determine the exact onset of symptoms by questioning the patient/witnesses.</li>
	<li>Ask for current medication with a main focus on anticoagulation therapy.</li>
	<li>Measure and log the vital signs, such as heart rate, blood pressure, blood sugar concentration, and oxygen saturation.</li>
</ol>
4. Insert a&#160;Peripheral Intravenous (IV) Line and Perform Blood Withdrawals
<ol>
	<li>Apply a tourniquet around the upper arm.</li>
	<li>Search for a suitable hand, forearm, or antecubital vein. The best choice for the iv line is a vein on the dorsum of the hand.</li>
	<li>Disinfect the skin.</li>
	<li>Remove needle sheath from the indwelling venous catheter. Ensure needle bevel is upwards.</li>
	<li>Apply traction distal to the vein to prevent vein from rolling during cannulation.</li>
	<li>Insert the needle into the vein at 20-40&#176;. The flashback of blood confirms that the needle tip is inside the vein. Advance the catheter off the needle into the vein.</li>
	<li>Fix the catheter using adhesive tape.</li>
	<li>Remove the needle, discard it to a sharps container and connect a plastic adapter containing a shrouded needle, which enables to start with a blood draw from the indwelling venous catheter.</li>
	<li>Perform blood draw using several Vacutainer blood test tubes. Some of these blood tubes contain different anticoagulatory additives, such as EDTA, citrate and heparine. The type of blood test tube is color-coded: 1. Purple for complete blood counts; 2. Blue for coagulatory assays; 3. Green for electrolytes, BUN, and other basic blood parameters; 4. Orange for specialized serum analysis.</li>
	<li>Push a Vacutainer blood test tube into the plastic holder, so that its rubber cap is pierced by the shrouded needle. (The negative pressure in the Vacutainer tubes forces blood into the blood test tubes.)</li>
	<li>Remove the Vacutainer tube after it was filled with blood and repeat this procedure with the other Vacutainer tubes.</li>
	<li>After the last Vacutainer tube was filled, remove the tourniquet, flush the indwelling venous catheter with normal saline solution, and close the catheter using a closing cone.</li>
</ol>
5. Determine the International Normalized Ratio (INR), using a Bedside Point-of-care Analyzer
<ol>
	<li>Take a test strip from its container. Slide it into the guide in the direction indicated by the arrows.</li>
	<li>Take a lancet and twist the protective cap off. Press the tip of the lancet against the side of the fingertip and press the trigger button.</li>
	<li>Apply the blood sample on the target area of the test strip within 15 sec of sticking the fingertip. After a few seconds the result (INR) is displayed.</li>
	<li>Place the used strip and the lancet into containers for biohazards and sharps, respectively.</li>
</ol>
6. Advanced Diagnostics and Intervention
<ol>
	<li>Immediately transfer the patient into the STEMO vehicle.</li>
	<li>Position the patient on a stretcher.</li>
	<li>Insert the purple Vacutainer blood test tube into the point-of-care laboratory (Horiba ABX Micros 60). Measure additional blood parameters such as platelet count, total leukocyte count, erythrocyte count, hemoglobin concentration, hematocrit, electrolytes.</li>
	<li>Insert the patient&#39;s insurance card into the card reader (installed in the control room).</li>
	<li>Call the neuroradiologist on-call to discuss the indication for CT scanning and prepare for examination.</li>
	<li>Explain benefits and risks of CT scanning to the patient. Afterwards, obtain informed consent from the patient, if possible.</li>
	<li>Start the CT. CAUTION: X-ray radiation is released from the CT scanner. Radiology technician has to be in the shielded control room. The rest of the STEMO staff is requested to leave the vehicle during the examination in order to avoid unnecessary exposure to x-ray radiation (STEMO vehicle is lead covered). Furthermore, protective measures (eye protection) should be applied to the patient.</li>
	<li>Transmit the CT image via on-board telemetric infrastructure and request teleradiological support for decision making regarding diagnosis and therapy. (Parallel analysis of images in the STEMO by the neurologist.)</li>
	<li>Ask the patient for contraindications against thrombolytic therapy using a standardized check list.</li>
	<li>Explain benefits and possible risks of thrombolysis. Inform the patient that the treatment is part of a clinical study and obtain informed consent, if possible.</li>
</ol>
7. Administration of Recombinant Tissue Plasminogen Activator (rtPA or Alteplase)
<ol>
	<li>Calculate the dose of alteplase (trade name: Actilyse) based on the best approximation of bodyweight available. The recommended dose is 0.9 mg/kg bodyweight. Maximum dose is 90 mg6.</li>
	<li>Reconstitute the dry solid alteplase using the solvent provided. Use the transfer cannula, which must be introduced vertically into the rubber stopper of the phials and through the mark at its center.</li>
	<li>Dissolve the dry solid by gentle agitation.</li>
	<li>Initiate thrombolysis by administering 10% of the calculated total dose as a bolus injection over 1 min. Keep record of the point in time, when alteplase bolus is injected. CAUTION: Pay attention to immediate allergic responses following administration. Be prepared to administer antiallergic drugs (i.e. antihistaminics, high-dose glucocorticoids, catecholamines) in case of an acute allergic response. In general, alteplase should be used only by a physician experienced in the treatment of ischemic stroke6.</li>
	<li>Inject the remaining dose via an injection pump syringe continuously over 60 min (after evacuation of the tubing to avoid the injection of air bubbles).</li>
</ol>
8. Transportation of the Patient to a Suitable Hospital
<ol>
	<li>Make an advanced notification to the emergency room of the closest hospital with a certified stroke unit.</li>
	<li>Start the transportation immediately. Communicate the selected hospital to the dispatch center via radio.</li>
	<li>Monitor neurological deficits and vital signs during transfer to the hospital.</li>
	<li>Print&#160;out and sign the admission letter (using Vimed software) including diagnosis, history, results of neurological examination, neuroradiological report (sent by the neuroradiologist on call via UMTS), results of laboratory investigations, and description of actions taken. Copy CT-scan on a CD for the hospital.</li>
	<li>On arrival at the hospital (press status button 8) provide concise present and past medical histories of the patient to the neurologist on-call and to the primary team in the Emergency Room. Hand over printed report, CD containing CT images (step&#160;8.4), and the blood-filled blue, green and orange Vacutainer blood test tubes (step&#160;4.9).</li>
</ol>
9. Restoring the Operational Readiness
<ol>
	<li>Clean and disinfect hands and all equipment that has been used during the EMS response.</li>
	<li>Report operational stand-by status to the dispatch center using button 1 on the onboard radio. Return to the local fire station.</li>
</ol>

<ol>
	<li>Meretoja, A., Strbian, D., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Reducing+in-hospital+delay+to+20+min+in+stroke+thrombolysis.">Reducing in-hospital delay to 20 min in stroke thrombolysis.</a> Neurology. 79 (4), 306-313 (2012).</li><li>Herlitz, J., Wireklintsundstr&#246;m, B., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Early+identification+and+delay+to+treatment+in+myocardial+infarction+and+stroke:+differences+and+similarities.">Early identification and delay to treatment in myocardial infarction and stroke: differences and similarities.</a> Scand. J. Trauma Resusc. Emerg. Med. 18 (48), (2010).</li><li>Worthmann, H., Schwartz, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Educational+campaign+on+stroke+in+an+urban+population+in+Northern+Germany:+influence+on+public+stroke+awareness+and+knowledge.">Educational campaign on stroke in an urban population in Northern Germany: influence on public stroke awareness and knowledge.</a> Int. J. Stroke. , (2012).</li><li>K&#246;hrmann, M., Schellinger, P. D., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Avoiding+in+hospital+delays+and+eliminating+the+three-hour+effect+in+thrombolysis+for+stroke.">Avoiding in hospital delays and eliminating the three-hour effect in thrombolysis for stroke.</a> Int. J. Stroke. 6, 493-497 (2011).</li><li>Ford, A. L., Williams, J. A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Reducing+Door-to-Needle+Times+Using+Toyota's+Lean+Manufacturing+Principles+and+Value+Stream+Analysis.">Reducing Door-to-Needle Times Using Toyota's Lean Manufacturing Principles and Value Stream Analysis.</a> Stroke. , (2012).</li><li>Committee ESOEECEW, ., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Guidelines+for+management+of+ischaemic+stroke+and+transient+ischaemic+attack.">Guidelines for management of ischaemic stroke and transient ischaemic attack.</a> Cerebrovasc. 25 (5), 457-507 (2008).</li><li>Gierhake, D., Weber, J. E., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Mobile+CT:+Technical+Aspects+of+Prehospital+Stroke+Imaging+before+Intravenous+Thrombolysis.">Mobile CT: Technical Aspects of Prehospital Stroke Imaging before Intravenous Thrombolysis.</a> Rofo. , (2012).</li><li>Ebinger, M., Rozanski, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=PHANTOM-S:+the+prehospital+acute+neurological+therapy+and+optimization+of+medical+care+in+stroke+patients+-+study.">PHANTOM-S: the prehospital acute neurological therapy and optimization of medical care in stroke patients - study.</a> Int. J. Stroke. 7 (4), 348-353 (2012).</li><li>Krebes, S., Ebinger, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Development+and+Validation+of+a+Dispatcher+Identification+Algorithm+for+Stroke+Emergencies+(DIASE).">Development and Validation of a Dispatcher Identification Algorithm for Stroke Emergencies (DIASE).</a> Stroke. 43 (3), 776-781 (2012).</li><li>Weber, J. E., Ebinger, M., Rozanski, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Pre-hospital+thrombolysis+in+acute+stroke+-+results+of+the+PHANTOM-S+pilot+study.">Pre-hospital thrombolysis in acute stroke - results of the PHANTOM-S pilot study.</a> Neurology. , (2012).</li><li>Walter, S., Kostopoulos, P., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Diagnosis+and+treatment+of+patients+with+stroke+in+a+mobile+stroke+unit+versus+in+hospital:+a+randomised+controlled+trial.">Diagnosis and treatment of patients with stroke in a mobile stroke unit versus in hospital: a randomised controlled trial.</a> Lancet Neurol. 11 (5), 397-404 (2012).</li><li>Thim, T., Krarup, N. H., Grove, E. L., Rohde, C. V., Loefgren, B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Initial+assessment+and+treatment+with+the+Airway,+Breathing,+Circulation,+Disability,+Exposure+(ABCDE)+approach.">Initial assessment and treatment with the Airway, Breathing, Circulation, Disability, Exposure (ABCDE) approach.</a> Int. J. Gen. Med. 5, 117-121 (2013).</li><li>Saver, J. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Time+Is+Brain+-+Quantified.">Time Is Brain - Quantified.</a> Stroke. 37 (1), 263-266 (2006).</li><li>Lees, K. R., Bluhmki, E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Time+to+treatment+with+intravenous+alteplase+and+outcome+in+stroke:+an+updated+pooled+analysis+of+ECASS,+ATLANTIS,+NINDS,+and+EPITHET+trials.">Time to treatment with intravenous alteplase and outcome in stroke: an updated pooled analysis of ECASS, ATLANTIS, NINDS, and EPITHET trials.</a> Lancet. 375 (9727), 1695-1703 (2010).</li><li>Rothwell, P. M., Buchan, A. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Mobile+acute+stroke+units:+bringing+the+hospital+to+the+patient.">Mobile acute stroke units: bringing the hospital to the patient.</a> Lancet Neurol. 11 (5), 382-383 (2012).</li></ol>

The authors declare that they have no competing financial interests.

Prehospital thrombolysis may be able to revolutionize acute specific stroke treatment. However, it is a cost and resource consuming way of treatment delivery. In general, a &#39;stay-and-play&#39; rather than a &#39;load-and-go&#39; approach needs to be justified by specific characteristics of the emergency at hand. Ischemic stroke has distinctive features that warrant a &#39;treat-and-run&#39; compromise: The benefits of acute stroke treatment are enormously time dependent. During an ischemic stroke approximately 2,000,000 neurons die per minute14. Intravenous treatment with rtPA enhances the chances of reperfusion and favorable functional outcome in stroke patients15. Treatment should be started as soon as possible. By now, it is the only evidence-based, effective and approved treatment for acute ischemic stroke. Associated with the risk of severe bleeding, the exclusion of intracranial bleeds and other contraindications is mandatory prior to thrombolysis. STEMO is set up to prove that this specific treatment can be safely administered in a prehospital setting and actually safes time compared to regular care8,11. First results from 12 prehospital thrombolyses in the Saarland State, Germany, seem promising in this respect12. In this study, Walter and colleagues reported that after randomized weeks between November, 2008, and July, 2011 and an interim analysis at 100 of 200 planned patients (53 in the prehospital setting, 47 in the control group), the median time from alarm to therapy decision (primary end-point) was substantially reduced in the 12 cases of prehospital thrombolysis: 35 min (IQR 31-39) versus 76 min, p&#60;0.0001; median difference 41 min (95% CI 36-48 min). Overall, the additional costs have to be weighed against benefits that patients may experience. For this, the final results of the ongoing PHANTOM-S will be crucial. In this prospective study (<a href="http://clinicaltrials.gov/ct2/show/" target="_blank">http://clinicaltrials.gov/ct2/show/</a> NCT01382862), weeks with and without STEMO on duty are randomized until 228 patients have received iv rtPA in both treatment arms. Primary end-point of the study is time from alarm to thrombolysis. Secondary end-points include modified Rankin Scale score after three months, symptomatic intracranial hemorrhage, mortality and cost effectiveness. Results of this study will help decision makers whether to implement prehospital thrombolysis of acute ischemic stroke patients with specialized ambulances in their emergency systems. Site specific adaptations may be necessary. For instance, in regions with a shortage of neurologists telemedicine may provide the expertise to the emergency physician on board. Similarly, the results of the PHANTOM-S study may help to identify regions with the most likely benefit for patients and cost effectiveness for authorities. So far, it is not known whether prehospital thrombolysis is the most appropriate approach in mega-cities, urban, or rural settings16. Taken together, prehospital thrombolysis seems to be a logical step when the need of shortening time to treatment is taken seriously. Only a sufficiently powered study may provide the evidence of actual benefit to stroke patients.

Thrombolysis with intravenous recombinant tissue Plasminogen Activator (rtPA) is the only proven effective treatment in acute ischemic stroke. The benefits of thrombolysis are time-dependent. Efficacy of thrombolytic therapy for ischemic stroke decreases with time elapsed from symptom onset1. Therefore, delays until initiation of treatment must be avoided. However, there are prehospital and in-hospital reasons for delays in treatment initiation. Patients&#39; decision time to call emergency services and the time from emergency call to arrival at the hospital are factors in the prehospital delay. In hospital, reductions of both the time to CT scanning and of the time between CT scan and start of thrombolysis remain challenging2. Stroke awareness campaigns shorten patient related times to emergency call3, but effects are only temporary and require repetition of such campaigns. While there are successful examples of reducing in-hospital delay&#160;4,5 many centers struggle to remain within the required 60 min from door to needle. One way to avoid these delays may be a start of specific stroke treatment at the emergency site, i.e. prehospital thrombolysis. Until recently, several requirements made this unfeasible. First, only physicians experienced in stroke care are qualified to make acute treatment decisions. Second, computed tomography (CT) is necessary to rule out intracranial hemorrhage. Third, laboratory tests should be available to exclude coagulation disorders6. In order to overcome these challenges, a stroke emergency mobile (STEMO) was constructed. This special ambulance is equipped with a CT scanner, a point-of-care laboratory and an infrastructure for teleradiological support7. It is operated by a highly specialized crew consisting of experienced neurologists, paramedics of the Berlin Fire Brigade, and radiology technicians8. To meet the legal requirements and the requirements of the Berlin Medical Board, each neurologist involved completed an additional training in emergency medicine. Radiology technicians completed a three month formal training in emergency care9. STEMO has been integrated in public emergency medical services (EMS) provided by the Berlin Fire Brigade. For the identification of eligible patients with suspected stroke during the emergency call, a special interview algorithm was developed and integrated at the dispatcher level10. During a three months pilot-study, we demonstrated safety and feasibility11. Our colleagues from Homburg, Germany, recently published their experience with the first 12 prehospital thrombolysis in the Saarland State12. We believe that prehospital stroke care using STEMO can reduce the alarm-to-needle time compared to regular care ultimately leading to improved patients care. However, prior to implementation final results of sufficiently powered studies need to confirm safety and efficacy of this approach. Here we present the methods used in the &#34;prehospital acute neurological therapy and optimization of medical care in stroke patients&#34; study (PHANTOM-S).

<table border="1">
	<tbody>
		<tr>
			<td></td>
			<td></td>
			<td></td>
			<td>Drug</td>
		</tr>
		<tr>
			<td>Alteplase (rtPA)</td>
			<td>Boehringer-Ingelheim</td>
			<td></td>
			<td>Licensed drug</td>
		</tr>
		<tr>
			<td></td>
			<td></td>
			<td></td>
			<td>Table 1. Alteplase. Alteplase (tissue-Plasminogen Activator) is the only licensed drug for acute ischemic stroke that has proven effectiveness within 4.5 hr of symptom onset in randomized controlled trials.</td>
		</tr>
		<tr>
			<td></td>
			<td></td>
			<td></td>
			<td>Device</td>
		</tr>
		<tr>
			<td>ABX micros 60</td>
			<td>Horiba Medical</td>
			<td></td>
			<td>Point-of-care laboratory</td>
		</tr>
		<tr>
			<td>CereTom</td>
			<td>NeuroLogica</td>
			<td></td>
			<td>CT-Scanner</td>
		</tr>
		<tr>
			<td>CoaguChek XSPlus</td>
			<td>Roche</td>
			<td></td>
			<td>Handheld blood analyzer</td>
		</tr>
		<tr>
			<td>EBA 20</td>
			<td>HettichLab</td>
			<td></td>
			<td>centrifuge</td>
		</tr>
		<tr>
			<td>FastPack System</td>
			<td>Qualigen</td>
			<td></td>
			<td>Point-of-care immunoassay</td>
		</tr>
		<tr>
			<td>i-STAT</td>
			<td>Abbot</td>
			<td></td>
			<td>Handheld blood analyzer</td>
		</tr>
		<tr>
			<td>OptiStat</td>
			<td>Siemens</td>
			<td></td>
			<td>Contrast agent delivery system</td>
		</tr>
		<tr>
			<td>Pilot A2</td>
			<td>Fresenius</td>
			<td></td>
			<td>Infusion pump</td>
		</tr>
		<tr>
			<td>TGL 12.250 4 x 2 BL</td>
			<td>MAN</td>
			<td></td>
			<td>Vehicle chassis</td>
		</tr>
		<tr>
			<td>Van body</td>
			<td>Fahrtec Systeme GmbH</td>
			<td></td>
			<td>Custom-built</td>
		</tr>
		<tr>
			<td>Vimed COMM</td>
			<td>MEYTEC GmbH</td>
			<td></td>
			<td>Video communication system</td>
		</tr>
		<tr>
			<td>Vimed GATEWAY</td>
			<td>MEYTEC GmbH</td>
			<td></td>
			<td>Network solution</td>
		</tr>
		<tr>
			<td>Vimed STEMO-DOC</td>
			<td>MEYTEC GmbH</td>
			<td></td>
			<td>Documentation software</td>
		</tr>
		<tr>
			<td>Vimed TELEMED</td>
			<td>MEYTEC GmbH</td>
			<td></td>
			<td>Equipment for telemedicine</td>
		</tr>
		<tr>
			<td>Vimed WEB-ENTRY</td>
			<td>MEYTEC GmbH</td>
			<td></td>
			<td>Teleradiology</td>
		</tr>
		<tr>
			<td></td>
			<td></td>
			<td></td>
			<td>Table 2. Table of specific equipment. The software solution used in the ambulance was developed by a partner of the STEMO-consortium, MEYTEC GmbH, Germany. MEYTEC designed and implemented the overall technical solution. The entire system can be obtained from the partner MEYTEC under the name VIMED STEMO.</td>
		</tr>
	</tbody>
</table>

prehospital thrombolysis: a manual from berlin

In acute ischemic stroke, time from symptom onset to intervention is a decisive prognostic factor. In order to reduce this time, prehospital thrombolysis at the emergency site would be preferable. However, apart from neurological expertise and laboratory investigations a computed tomography (CT) scan is necessary to exclude hemorrhagic stroke prior to thrombolysis. Therefore, a specialized ambulance equipped with a CT scanner and point-of-care laboratory was designed and constructed. Further, a new stroke identifying interview algorithm was developed and implemented in the Berlin emergency medical services. Since February 2011 the identification of suspected stroke in the dispatch center of the Berlin Fire Brigade prompts the deployment of this ambulance, a stroke emergency mobile (STEMO). On arrival, a neurologist, experienced in stroke care and with additional training in emergency medicine, takes a neurological examination. If stroke is suspected a CT scan excludes intracranial hemorrhage. The CT-scans are telemetrically transmitted to the neuroradiologist on-call. If coagulation status of the patient is normal and patient&#39;s medical history reveals no contraindication, prehospital thrombolysis is applied according to current guidelines (intravenous recombinant tissue plasminogen activator, iv rtPA, alteplase, Actilyse).
Thereafter patients are transported to the nearest hospital with a certified stroke unit for further treatment and assessment of strokeaetiology. After a pilot-phase, weeks were randomized into blocks either with or without STEMO care. Primary end-point of this study is time from alarm to the initiation of thrombolysis. We hypothesized that alarm-to-treatment time can be reduced by at least 20 min compared to regular care.

From February 8 to April 30, 2011, a total of 152 subjects were treated in the STEMO vehicle. Informed consent was obtained from 77 patients. Forty-five patient&#39;s (58%) had an acute ischemic stroke and 23 (51%) of these patients received rtPA. The mean alarm-to-needle time using STEMO was 62 min compared to 98 min in a control cohort of 50 consecutive patients thrombolysed in Berlin in 2010. Two (9%) of the rtPA-treated patients suffered a symptomatic intracranial hemorrhage and one of these patients (4%) died in hospital. Technical failures comprised one CT dysfunction and two delayed CT-image transmissions11.
<img alt="Figure 1" fo:content-width="5in" fo:src="/files/ftp_upload/50534/50534fig1highres.jpg" src="/files/ftp_upload/50534/50534fig1.jpg" /> 
Figure 1. Call-to-needle-time. Comparison of acute ischemic stroke patients who received tissue-Plasminogen Activator (tPA). STEMO-treated patients (n=23) vs. in-hospital treated patients in 2010 (n=50). Boxes show standard deviation (SD) with the line representing the mean call-to-needle time (62 minutes vs. 98 minutes); whiskers indicate the distribution width within 2 x SD. Based on data from Weber et al.11&#160;<a href="https://www.jove.com/files/ftp_upload/50534/50534fig1highres.jpg" target="_blank">Click here to view larger figure</a>.
<img alt="Figure 2" fo:content-width="5in" fo:src="/files/ftp_upload/50534/50534fig2highres.jpg" src="/files/ftp_upload/50534/50534fig2.jpg" /> 
Figure 2. STEMO overall concept. Flow diagram of EMS response with main focus on stroke emergencies responded by STEMO. Modified according to an original design by Audebert, H.J. STEMO (Stroke-Einsatz-Mobil). <a href="http://tsb-berlin.de /media/uploads/zukunfsfonds/STEMO_(Stroke-Einsatz-Mobil).pdf" target="_blank">http://tsb-berlin.de /media/uploads/zukunfsfonds/STEMO_(Stroke-Einsatz-Mobil).pdf</a>. <a href="https://www.jove.com/files/ftp_upload/50534/50534fig2highres.jpg" target="_blank"> Click here to view larger figure</a>.

Watch this Scientific Journal Video about Prehospital Thrombolysis: A Manual from Berlin at JoVE.com

Prehospital Thrombolysis: A Manual from Berlin

Identification of suspected stroke in the dispatch center of the Berlin Fire Brigade prompts the deployment of a CT-equipped ambulance. If ischemic stroke is confirmed and contraindications are excluded prehospital thrombolysis is applied.

In acute ischemic stroke, time from symptom onset to intervention is a decisive prognostic factor. In order to reduce this time, prehospital thrombolysis ...

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20.4K Views.  Charité - Universitätsmedizin Berlin. Identification of suspected stroke in the dispatch center of the Berlin Fire Brigade prompts the deployment of a CT-equipped ambulance. If ischemic stroke is confirmed and contraindications are excluded prehospital thrombolysis is applied.

Video: Prehospital Thrombolysis: A Manual from Berlin

Manual Muscle Testing:  A Method of Measuring Extremity Muscle Strength Applied to Critically Ill Patients

Survivors of acute respiratory distress syndrome (ARDS) and other causes of critical illness often have generalized weakness, reduced exercise tolerance, and persistent nerve and muscle impairments after hospital discharge.1-6 Using an explicit protocol with a structured approach to training and quality assurance of research staff, manual muscle testing (MMT) is a highly reliable method for assessing strength, using a standardized clinical examination, for patients following ARDS, and can be completed with mechanically ventilated patients who can tolerate sitting upright in bed and are able to follow two-step commands. 7, 8 
This video demonstrates a protocol for MMT, which has been taught to &ge;43 research staff who have performed &gt;800 assessments on &gt;280 ARDS survivors. Modifications for the bedridden patient are included. Each muscle is tested with specific techniques for positioning, stabilization, resistance, and palpation for each score of the 6-point ordinal Medical Research Council scale.7,9-11 Three upper and three lower extremity muscles are graded in this protocol: shoulder abduction, elbow flexion, wrist extension, hip flexion, knee extension, and ankle dorsiflexion. These muscles were chosen based on the standard approach for evaluating patients for ICU-acquired weakness used in prior publications. 1,2.

Survivors of acute respiratory distress syndrome (ARDS) and critical illness frequently develop long-lasting muscle weakness. Manual muscle testing (MMT) is a standardized clinical examination commonly used to measure strength of peripheral skeletal muscle groups. This video demonstrates MMT using the 6-point Medical Research Council scale.

Survivors of acute respiratory distress syndrome (ARDS) and other causes of critical illness often have generalized weakness, reduced exercise tolerance, ...

Bilateral Common Carotid Artery Occlusion as an Adequate Preconditioning Stimulus to Induce Early Ischemic Tolerance to Focal Cerebral Ischemia

There is accumulating evidence, that ischemic preconditioning - a non-damaging ischemic challenge to the brain - confers a transient protection to a subsequent damaging ischemic insult. We have established bilateral common carotid artery occlusion as a preconditioning stimulus to induce early ischemic tolerance to transient focal cerebral ischemia in C57Bl6/J mice. In this video, we will demonstrate the methodology used for this study.

There is accumulating evidence, that ischemic preconditioning (PC) &#x2013; a non-damaging ischemic challenge to the brain - confers a transient protection to a subsequent damaging ischemic insult. We established bilateral common carotid artery occlusion (BCCAO) as a preconditioning stimulus to induce early ischemic tolerance (IT) to transient focal cerebral ischemia (induced by middle cerebral artery occlusion, MCAO) in C57Bl6/J mice.

There is accumulating evidence, that ischemic preconditioning - a non-damaging ischemic challenge to the brain - confers a transient protection to a ...

Driving Simulation in the Clinic: Testing Visual Exploratory Behavior in Daily Life Activities in Patients with Visual Field Defects

Patients suffering from homonymous hemianopia after infarction of the posterior cerebral artery (PCA) report different degrees of constraint in daily life, despite similar visual deficits. We assume this could be due to variable development of compensatory strategies such as altered visual scanning behavior. Scanning compensatory therapy (SCT) is studied as part of the visual training after infarction next to vision restoration therapy. SCT consists of learning to make larger eye movements into the blind field enlarging the visual field of search, which has been proven to be the most useful strategy1, not only in natural search tasks but also in mastering daily life activities2. Nevertheless, in clinical routine it is difficult to identify individual levels and training effects of compensatory behavior, since it requires measurement of eye movements in a head unrestrained condition. Studies demonstrated that unrestrained head movements alter the visual exploratory behavior compared to a head-restrained laboratory condition3. Martin et al.4 and Hayhoe et al.5 showed that behavior demonstrated in a laboratory setting cannot be assigned easily to a natural condition. Hence, our goal was to develop a study set-up which uncovers different compensatory oculomotor strategies quickly in a realistic testing situation: Patients are tested in the clinical environment in a driving simulator. SILAB software (Wuerzburg Institute for Traffic Sciences GmbH (WIVW)) was used to program driving scenarios of varying complexity and recording the driver's performance. The software was combined with a head mounted infrared video pupil tracker, recording head- and eye-movements (EyeSeeCam, University of Munich Hospital, Clinical Neurosciences).
The positioning of the patient in the driving simulator and the positioning, adjustment and calibration of the camera is demonstrated. Typical performances of a patient with and without compensatory strategy and a healthy control are illustrated in this pilot study. Different oculomotor behaviors (frequency and amplitude of eye- and head-movements) are evaluated very quickly during the drive itself by dynamic overlay pictures indicating where the subjects gaze is located on the screen, and by analyzing the data. Compensatory gaze behavior in a patient leads to a driving performance comparable to a healthy control, while the performance of a patient without compensatory behavior is significantly worse. The data of eye- and head-movement-behavior as well as driving performance are discussed with respect to different oculomotor strategies and in a broader context with respect to possible training effects throughout the testing session and implications on rehabilitation potential.

Patients with visual deficits after stroke report about different constraints in daily life most likely due to variable compensatory strategies, which are difficult to differentiate in clinical routine. We present a clinical set-up which allows measurement of different compensatory head- and eye-movement-strategies and evaluating their effects on driving performance.

Patients suffering from homonymous hemianopia after infarction of the posterior cerebral artery (PCA) report different degrees of constraint in daily ...

Patient Derived Cell Culture and Isolation of CD133+ Putative Cancer Stem Cells from Melanoma

Despite improved treatments options for melanoma available today, patients with advanced malignant melanoma still have a poor prognosis for progression-free and overall survival. Therefore, translational research needs to provide further molecular evidence to improve targeted therapies for malignant melanomas. In the past, oncogenic mechanisms related to melanoma were extensively studied in established cell lines. On the way to more personalized treatment regimens based on individual genetic profiles, we propose to use patient-derived cell lines instead of generic cell lines. Together with high quality clinical data, especially on patient follow-up, these cells will be instrumental to better understand the molecular mechanisms behind melanoma progression.
Here, we report the establishment of primary melanoma cultures from dissected fresh tumor tissue. This procedure includes mincing and dissociation of the tissue into single cells, removal of contaminations with erythrocytes and fibroblasts as well as primary culture and reliable verification of the cells' melanoma origin.
Recent reports revealed that melanomas, like the majority of tumors, harbor a small subpopulation of cancer stem cells (CSCs), which seem to exclusively fuel tumor initiation and progression towards the metastatic state. One of the key markers for CSC identification and isolation in melanoma is CD133. To isolate CD133+ CSCs from primary melanoma cultures, we have modified and optimized the Magnetic-Activated Cell Sorting (MACS) procedure from Miltenyi resulting in high sorting purity and viability of CD133+ CSCs and CD133- bulk, which can be cultivated and functionally analyzed thereafter.

Patient Derived Cell Culture and Isolation of CD133+ Putative Cancer Stem Cells from Melanoma

This article describes the preparation of freshly obtained melanoma tissue into primary cell cultures, and how to remove contaminations of erythrocytes and fibroblasts from the tumor cells. Finally, we describe how CD133+ putative melanoma stem cells are sorted from the CD133- bulk using Magnetic Activated Cell Sorting (MACS).

Despite improved treatments options for melanoma available today, patients with advanced malignant melanoma still have a poor prognosis for ...

Assessment of Cardiac Function and Myocardial Morphology Using Small Animal Look-locker Inversion Recovery (SALLI) MRI in Rats

Small animal magnetic resonance imaging is an important tool to study cardiac function and changes in myocardial tissue. The high heart rates of small animals (200 to 600 beats/min) have previously limited the role of CMR imaging. Small animal Look-Locker inversion recovery (SALLI) is a T1 mapping sequence for small animals to overcome this problem 1. T1 maps provide quantitative information about tissue alterations and contrast agent kinetics. It is also possible to detect diffuse myocardial processes such as interstitial fibrosis or edema 1-6. Furthermore, from a single set of image data, it is possible to examine heart function and myocardial scarring by generating cine and inversion recovery-prepared late gadolinium enhancement-type MR images 1.
	The presented video shows step-by-step the procedures to perform small animal CMR imaging. Here it is presented with a healthy Sprague-Dawley rat, however naturally it can be extended to different cardiac small animal models.

Assessment of Cardiac Function and Myocardial Morphology Using Small Animal Look-locker Inversion Recovery SALLI MRI in Rats

Contrast enhanced cardiac magnetic resonance (CMR) imaging allows comprehensive in vivo assessment of the heart in small animal models of cardiovascular disease. Here we detail the procedures to perform CMR imaging, reconstruction and analysis using Small Animal Lock-Locker Inversion Recovery (SALLI) in rats.

Small animal magnetic resonance  imaging is an important tool to study cardiac function and changes in myocardial  tissue. The high heart rates of small ...

Lavage-induced Surfactant Depletion in Pigs As a Model of the Acute Respiratory Distress Syndrome (ARDS)

Various animal models of lung injury exist to study the complex pathomechanisms of human acute respiratory distress syndrome (ARDS) and evaluate future therapies. Severe lung injury with a reproducible deterioration of pulmonary gas exchange and hemodynamics can be induced in anesthetized pigs using repeated lung lavages with warmed 0.9% saline (50 ml/kg body weight). Including standard respiratory and hemodynamic monitoring with clinically applied devices in this model allows the evaluation of novel therapeutic strategies (drugs, modern ventilators, extracorporeal membrane oxygenators, ECMO), and bridges the gap between bench and bedside. Furthermore, induction of lung injury with lung lavages does not require the injection of pathogens/endotoxins that impact on measurements of pro- and anti-inflammatory cytokines. A disadvantage of the model is the high recruitability of atelectatic lung tissue. Standardization of the model helps to avoid pitfalls, to ensure comparability between experiments, and to reduce the number of animals needed.

Lavage-induced Surfactant Depletion in Pigs As a Model of the Acute Respiratory Distress Syndrome ARDS

Repeated pulmonary lavages in anesthetized pigs induce lung injury resembling major aspects of human acute respiratory distress syndrome (ARDS). For this purpose the lungs are repeatedly lavaged with 0.9% saline at 37 &#176;C. The goal of the protocol is a reproducible mitigation of gas exchange and hemodynamics for research in ARDS.

Various animal models of lung injury exist to study the complex pathomechanisms of human acute respiratory distress syndrome (ARDS) and evaluate future ...

Discovering Middle Ear Anatomy by Transcanal Endoscopic Ear Surgery: A Dissection Manual

The middle ear is located in the center of the temporal bone and bears a highly complex anatomy. The recently introduced exclusively endoscopic transcanal approach to the middle ear is a minimally invasive technique sparing the bone and mucosa of the mastoid bone, since the middle ear is accessed through the external auditory canal. This emerging method has several advantages over the traditional (microscopic) approaches to the middle ear such as the panoramic wide-angle views of the anatomy, the possibility to approach and magnify tiny structures, and the possibility of looking around the corner using angled endoscopes.
The cadaveric dissection method presented here consists of an overview on the technical requirements and a precise description of a step-by-step protocol to discover the anatomy of the middle ear. Each step and anatomical structure is carefully described in order to provide a comprehensive guide to endoscopic ear anatomy. In our opinion, this is particularly important to any novice in endoscopic ear surgery as it provides thorough anatomical knowledge and may improve surgical skills.

The aim of this article is to describe the methodology of exclusively endoscopic cadaveric middle ear dissection. Moreover, we aim to provide a comprehensive guide to endoscopic middle ear anatomy.

The middle ear is located in the center of the temporal bone and bears a highly complex anatomy. The recently introduced exclusively endoscopic transcanal ...

Sucrose Preference and Novelty-Induced Hypophagia Tests in Rats using an Automated Food Intake Monitoring System

The prevalence and incidence of depressive disorders are rising worldwide, affecting about 322 million individuals, underlining the need for behavioral studies in animal models. In this protocol, to study depression-like and anhedonic behavior in rats, the established sucrose preference and novelty-induced hypophagia tests are combined with an automated food and liquid intake monitoring system. Prior to testing, in the sucrose preference paradigm, male rats are trained for at least 2 days to consume a sucrose solution in addition to tap water. During the test, rats are again exposed to water and sucrose solution. Consumption is registered every second by the automated system. The ratio of sucrose to total water intake (sucrose preference ratio) is a surrogate parameter for anhedonia. In the novelty-induced hypophagia test, male rats undergo a training period in which they are exposed to a palatable snack. During training, rodents show a stable baseline snack intake. On test day, the animals are transferred from home cages into a fresh, empty cage representing a novel unknown environment with access to the known palatable snack. The automated system records the total intake and its underlying microstructure (e.g., latency to approaching the snack), providing insight into anhedonic and anxious behaviors. The combination of these paradigms with an automated measuring system provides more detailed information, along with higher accuracy by reducing measuring errors. However, the tests use surrogate parameters and only depict depression and anhedonia in an indirect manner.

Presented here is a protocol to study depression-like and anhedonic behavior in rats. It combines two well-established behavioral methods, the sucrose preference and novelty-induced hypophagia tests, with an automated food and liquid intake monitoring system, to indirectly investigate rodent behavior using surrogate parameters.

The prevalence and incidence of depressive disorders are rising worldwide, affecting about 322 million individuals, underlining the need for behavioral ...

Digital Home-Monitoring of Patients after Kidney Transplantation: The MACCS Platform

The MACCS (Medical Assistant for Chronic Care Service) platform enables secure sharing of key medical information between patients after kidney transplantation and physicians. Patients provide information such as vital signs, well-being, and medication intake via smartphone apps. The information is transferred directly into a database and electronic health record at the kidney transplant center, which is used for routine patient care and research. Physicians can send an updated medication plan and laboratory data directly to the patient app via this secure platform. Other features of the app are medical messages and video consultations. Consequently, the patient is better-informed, and self-management is facilitated. In addition, the transplant center and the patient's local nephrologist automatically exchange notes, medical reports, laboratory values, and medication data via the platform. A telemedicine team reviews all incoming data on a dashboard and takes action, if necessary. Tools to identify patients at risk for complications are under development. The platform exchanges data via a standardized secure interface (Health Level 7 (HL7), Fast Healthcare Interoperability Resources (FHIR)). The standardized data exchange based on HL7 FHIR guarantees interoperability with other eHealth solutions and allows rapid scalability to other chronic diseases. The underlying data protection concept is in concordance with the latest European General Data Protection Regulation. Enrollment started in February 2020, and 131 kidney transplant recipients are actively participating as of July 2020. Two large German health insurance companies are currently funding the telemedicine services of the project. The deployment for other chronic kidney diseases and solid organ transplant recipients is planned. In conclusion, the platform is designed to enable home monitoring and automatic data exchange, empower patients, reduce hospitalizations, and improve adherence, and outcomes after kidney transplantation.

The MACCS platform&#160;is a comprehensive telemedicine concept aiming at better outcomes after kidney transplantation by sharing key medical information between patients and physicians. A telemedicine team reviews incoming data to detect potential complications and to improve adherence in kidney transplant recipients to achieve better long-term outcomes.

The MACCS (Medical Assistant for Chronic Care Service) platform enables secure sharing of key medical information between patients after kidney ...

A Simplified Stepwise Approach to Echo Guidance during Percutaneous Mitral Valve Repair

Percutaneous transcatheter edge-to-edge reconstruction of the mitral valve is a safe and well-established therapy for severe symptomatic mitral regurgitation in patients with high surgical risk. Echocardiographic guidance in addition to fluoroscopy is the gold standard and should be performed using a standardized technique.
This article lays out our reproducible step by step echocardiographic guide including views, measurements as well as highlighting possible difficulties that may arise during the procedure.
This article provides detailed and chronological echocardiographic views for each step of the procedure, especially preferences between 2D and 3D imaging. If needed, pulse wave, continuous wave and color doppler measurements are described. Furthermore, as there are no official recommendations for the quantification of mitral regurgitation during the percutaneous edge-to-edge-repair procedure, advice is also included for echocardiographic quantification after grasping the mitral leaflets and after device deployment. In addition, the article deals with important echocardiographic views to prevent and deal with possible complications during the procedure.
Echocardiographic guidance during transcatheter mitral valve repair is mandatory. A structured approach improves the collaboration between interventionist and imager and is indispensable for a safe and effective procedure.

This protocol presents in detail how to perform real-time echocardiographic guidance during transcatheter mitral valve repair. The fundamental views and the necessary measurements are described for each stage of the procedure.