Variation in structure and process of care in traumatic brain injury : Provider profiles of European Neurotrauma Centers participating in the CENTER-TBI study

Funding Information: Data used in preparation of this manuscript were obtained in the context of CENTER-TBI, a large collaborative project with the support of the European Commission 7th Framework program (602150). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors would like to thank all CENTER-TBI investigators and their staff, who are listed below, for completing the provider profiling questionnaires. Authors would further like to thank Nada Andelic, Sasha Brazinova, Ruben van der Brande, Peter Cameron, Guiseppe Citerio, Ari Ercole, Thomas van Essen, Mathieu van der Jagt, Erwin Kompanje, Fiona Lecky, Joukje van der Naalt, David Nelson, Wilco Peul, Jukka Ranta, Cecilia Roe, Gerard Ribbers, Nino Stochetti, Olli Tenovuo and Lindsay Wilson for their help with the development of the provider profiling questionnaires. Publisher Copyright: © 2016 Cnossen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Introduction: The strength of evidence underpinning care and treatment recommendations in traumatic brain injury (TBI) is low. Comparative effectiveness research (CER) has been proposed as a framework to provide evidence for optimal care for TBI patients. The first step in CER is to map the existing variation. The aim of current study is to quantify variation in general structural and process characteristics among centers participating in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. Methods: We designed a set of 11 provider profiling questionnaires with 321 questions about various aspects of TBI care, chosen based on literature and expert opinion. After pilot testing, questionnaires were disseminated to 71 centers from 20 countries participating in the CENTER-TBI study. Reliability of questionnaires was estimated by calculating a concordance rate among 5% duplicate questions. Results: All 71 centers completed the questionnaires. Median concordance rate among duplicate questions was 0.85. The majority of centers were academic hospitals (n = 65, 92%), designated as a level I trauma center (n = 48, 68%) and situated in an urban location (n = 70, 99%). The availability of facilities for neuro-trauma care varied across centers; e.g. 40 (57%) had a dedicated neuro-intensive care unit (ICU), 36 (51%) had an in-hospital rehabilitation unit and the organization of the ICU was closed in 64% (n = 45) of the centers. In addition, we found wide variation in processes of care, such as the ICU admission policy and intracranial pressure monitoring policy among centers. Conclusion: Even among high-volume, specialized neurotrauma centers there is substantial variation in structures and processes of TBI care. This variation provides an opportunity to study effectiveness of specific aspects of TBI care and to identify best practices with CER approaches.publishersversionPeer reviewe

Postoperative survival in patients with multiple brain metastases

BACKGROUND AND OBJECTIVE: Although surgery is traditionally performed for patients with a single brain metastasis, an increasing number of patients with multiple brain metastases may also be treated surgically. The objective of the study was to analyze postoperative survival results and the clinical factors affecting these results. MATERIAL AND METHODS: The records of the patients who underwent surgical resection of 2 or more lesions between January 2005 and January 2010 were retrospectively reviewed. Survival was calculated from the date of surgery to the last follow-up evaluation or death, and different clinical factors were analyzed in regard to patient survival. RESULTS: In total, 36 patients underwent one or more craniotomies. The survival of the total group ranged from 16 days to 37.5 months (mean, 29 months). There were 4 deaths within 30 days. When divided into Radiation Therapy Oncology Group RPA classes, the survival time was 11.75, 8.58, and 5.31 months for classes 1, 2, and 3, respectively. Regarding an impact on the survival, a significant association with a favorable outcome was found for the following factors: the number of brain metastases (2-3 vs. 4-6, P=0.046), RPA classes (1 vs. 2 or 3, P=0.0192), and extent of metastasis resection (all vs. partial, P=0.018). CONCLUSIONS: Well-selected patients with multiple brain metastases appear to benefit from surgery compared with historical controls of patients treated with whole-brain radiotherapy alone.publishersversionPeer reviewe

Variation in Structure and Process of Care in Traumatic Brain Injury: Provider Profiles of European Neurotrauma Centers Participating in the CENTER-TBI Study.

INTRODUCTION: The strength of evidence underpinning care and treatment recommendations in traumatic brain injury (TBI) is low. Comparative effectiveness research (CER) has been proposed as a framework to provide evidence for optimal care for TBI patients. The first step in CER is to map the existing variation. The aim of current study is to quantify variation in general structural and process characteristics among centers participating in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. METHODS: We designed a set of 11 provider profiling questionnaires with 321 questions about various aspects of TBI care, chosen based on literature and expert opinion. After pilot testing, questionnaires were disseminated to 71 centers from 20 countries participating in the CENTER-TBI study. Reliability of questionnaires was estimated by calculating a concordance rate among 5% duplicate questions. RESULTS: All 71 centers completed the questionnaires. Median concordance rate among duplicate questions was 0.85. The majority of centers were academic hospitals (n = 65, 92%), designated as a level I trauma center (n = 48, 68%) and situated in an urban location (n = 70, 99%). The availability of facilities for neuro-trauma care varied across centers; e.g. 40 (57%) had a dedicated neuro-intensive care unit (ICU), 36 (51%) had an in-hospital rehabilitation unit and the organization of the ICU was closed in 64% (n = 45) of the centers. In addition, we found wide variation in processes of care, such as the ICU admission policy and intracranial pressure monitoring policy among centers. CONCLUSION: Even among high-volume, specialized neurotrauma centers there is substantial variation in structures and processes of TBI care. This variation provides an opportunity to study effectiveness of specific aspects of TBI care and to identify best practices with CER approaches

Variation in general supportive and preventive intensive care management of traumatic brain injury: a survey in 66 neurotrauma centers participating in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study

Abstract Background General supportive and preventive measures in the intensive care management of traumatic brain injury (TBI) aim to prevent or limit secondary brain injury and optimize recovery. The aim of this survey was to assess and quantify variation in perceptions on intensive care unit (ICU) management of patients with TBI in European neurotrauma centers. Methods We performed a survey as part of the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. We analyzed 23 questions focused on: 1) circulatory and respiratory management; 2) fever control; 3) use of corticosteroids; 4) nutrition and glucose management; and 5) seizure prophylaxis and treatment. Results The survey was completed predominantly by intensivists (n = 33, 50%) and neurosurgeons (n = 23, 35%) from 66 centers (97% response rate). The most common cerebral perfusion pressure (CPP) target was > 60 mmHg (n = 39, 60%) and/or an individualized target (n = 25, 38%). To support CPP, crystalloid fluid loading (n = 60, 91%) was generally preferred over albumin (n = 15, 23%), and vasopressors (n = 63, 96%) over inotropes (n = 29, 44%). The most commonly reported target of partial pressure of carbon dioxide in arterial blood (PaCO2) was 36–40 mmHg (4.8–5.3 kPa) in case of controlled intracranial pressure (ICP) < 20 mmHg (n = 45, 69%) and PaCO2 target of 30–35 mmHg (4–4.7 kPa) in case of raised ICP (n = 40, 62%). Almost all respondents indicated to generally treat fever (n = 65, 98%) with paracetamol (n = 61, 92%) and/or external cooling (n = 49, 74%). Conventional glucose management (n = 43, 66%) was preferred over tight glycemic control (n = 18, 28%). More than half of the respondents indicated to aim for full caloric replacement within 7 days (n = 43, 66%) using enteral nutrition (n = 60, 92%). Indications for and duration of seizure prophylaxis varied, and levetiracetam was mostly reported as the agent of choice for both seizure prophylaxis (n = 32, 49%) and treatment (n = 40, 61%). Conclusions Practice preferences vary substantially regarding general supportive and preventive measures in TBI patients at ICUs of European neurotrauma centers. These results provide an opportunity for future comparative effectiveness research, since a more evidence-based uniformity in good practices in general ICU management could have a major impact on TBI outcome

Variation in neurosurgical management of traumatic brain injury

Background: Neurosurgical management of traumatic brain injury (TBI) is challenging, with only low-quality evidence. We aimed to explore differences in neurosurgical strategies for TBI across Europe. Methods: A survey was sent to 68 centers participating in the Collaborative European Neurotrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. The questionnaire contained 21 questions, including the decision when to operate (or not) on traumatic acute subdural hematoma (ASDH) and intracerebral hematoma (ICH), and when to perform a decompressive craniectomy (DC) in raised intracranial pressure (ICP). Results: The survey was completed by 68 centers (100%). On average, 10 neurosurgeons work in each trauma center. In all centers, a neurosurgeon was available within 30 min. Forty percent of responders reported a thickness or volume threshold for evacuation of an ASDH. Most responders (78%) decide on a primary DC in evacuating an ASDH during the operation, when swelling is present. For ICH, 3% would perform an evacuation directly to prevent secondary deterioration and 66% only in case of clinical deterioration. Most respondents (91%) reported to consider a DC for refractory high ICP. The reported cut-off ICP for DC in refractory high ICP, however, differed: 60% uses 25 mmHg, 18% 30 mmHg, and 17% 20 mmHg. Treatment strategies varied substantially between regions, specifically for the threshold for ASDH surgery and DC for refractory raised ICP. Also within center variation was present: 31% reported variation within the hospital for inserting an ICP monitor and 43% for evacuating mass lesions. Conclusion: Despite a homogeneous organization, considerable practice variation exists of neurosurgical strategies for TBI in Europe. These results provide an incentive for comparative effectiveness research to determine elements of effective neurosurgical care

Postoperative Survival in Patients With Multiple Brain Metastases

Background and Objective. Although surgery is traditionally performed for patients with a single brain metastasis, an increasing number of patients with multiple brain metastases may also be treated surgically. The objective of the study was to analyze postoperative survival results and the clinical factors affecting these results. Material and Methods. The records of the patients who underwent surgical resection of 2 or more lesions between January 2005 and January 2010 were retrospectively reviewed. Survival was calculated from the date of surgery to the last follow-up evaluation or death, and different clinical factors were analyzed in regard to patient survival. Results. In total, 36 patients underwent one or more craniotomies. The survival of the total group ranged from 16 days to 37.5 months (mean, 29 months). There were 4 deaths within 30 days. When divided into Radiation Therapy Oncology Group RPA classes, the survival time was 11.75, 8.58, and 5.31 months for classes 1, 2, and 3, respectively. Regarding an impact on the survival, a significant association with a favorable outcome was found for the following factors: the number of brain metastases (2–3 vs. 4–6, P=0.046), RPA classes (1 vs. 2 or 3, P=0.0192), and extent of metastasis resection (all vs. partial, P=0.018). Conclusions. Well-selected patients with multiple brain metastases appear to benefit from surgery compared with historical controls of patients treated with whole-brain radiotherapy alone

Two and More Cerebral Metastases Complex Treatment Options. Doctoral Thesis

Promocijas darbs izstrādāts Rīgas Stradiņa universitātes Neiroloģijas un neiroķirurģijas katedras klīniskajā bāzē – Rīgas Austrumu klīniskās universitātes slimnīcas (RAKUS) klīnikā “Gaiļezers” (nodaļas vadītāji – dr. K. Bicāns, prof. J. Ozoliņš ) – sadarbībā ar Latvijas Onkoloģijas centra Terapeitiskās radioloģijas un medicīnas fizikas klīniku (vadītāja – Dr. med. docente O. Utehina) un Staru terapijas nodaļu (vadītāja – Z. Liepa). Radioloģiskā diagnostika un terapijas kontrole galvenokārt veikta Radioloģijas katedras klīniskajā bāzē – RAKUS klīnikā “Gaiļezers” (vadītāja – profesore G. Krūmiņa). Evakuēto cerebrālo metastāžu ģenētiskā analīze veikta sadarbībā ar Rīgas Stradiņa universitātes Onkoloģijas institūtu (vadītājs – profesors E. Miklaševičs). Aizstāvēšana: 2015. gada 10. jūnijā plkst. 15.00 Rīgas Stradiņa universitātes Medicīnas promocijas padomes atklātā sēdē Rīgā, Dzirciema ielā 16, Hipokrāta auditorijā.Promocijas darbs ir veltīts vienai no aktuālākajām mūsdienu neiroķirurģijas un onkoloģijas problēmām – vēža cerebrālu metastāžu ārstēšanas taktikai, kā arī iespējām uzlabot ārstēšanas rezultātus ar jaunākajiem pieejamajiem resursiem. Cerebrālās metastāzes ir visbiežāk sastopamais intrakraniālo audzēju veids. Uzlabojoties ekstrakraniālās patoloģijas ārstēšanas rezultātiem un kļūstot pieejamākiem neiroradioloģiskiem izmeklējumiem, diagnosticēto cerebrālo metastāžu skaitam ir tendence pieaugt. Pašreiz, arī Latvijā, cerebrālu metastāžu ārstēšanā ir iespējams pielietot jaunākās ārstēšanas metodes: ķirurģisku rezekciju, stereotaktisku radioķirurģiju, visu galvas smadzeņu apstarošanu (WBRT) un ķīmijterapiju. Ja pacientam ir viena cerebrāla metastāze, ārstēšanas taktika parasti ir standartizēta un tā ir maksimāli radikāla, iekļaujot kompleksas terapijas pielietojumu. Slimniekiem ar divām un vairākām cerebrālām metastāzēm līdz šim vēl nav atrodamas skaidras indikācijas ķirurģiskai un kompleksai terapijai. Mūsu pētījuma mērķis bija izanalizēt un savstarpēji salīdzināt divu un vairāku galvas smadzeņu metastāžu ķirurģiskas un kombinētas ārstēšanas iespējas un rezultātus, kā arī izvērtēt pirmos galvas smadzeņu metastāžu radioķirurģiskās ārstēšanas rezultātus Latvijā. Retrospektīvā pētījumā tika analizēti dati par 40 pacientiem, kuri ārstēti ķirurģiski (14 no tiem pēcoperācijas periodā saņēma kompleksu terapiju), un Latvijā pirmajiem 16 radioķirurģisku terapiju saņēmušiem pacientiem, kuri ārstēti Rīgas Austrumu klīniskās universitātes slimnīcas klīniskajās bāzēs laika periodā no 2005. līdz 2012. gadam. Tika vērtēti pacientu ārstēšanas rezultāti un dzīvildze atkarībā no klīniskajiem un radioloģiskajiem kritērijiem un pielietotās ārstēšanas taktikas, kā arī veikta visu evakuēto cerebrālo metastāžu ģenētiskā materiāla analīze klīniski nozīmīgu TP53 gēna mutāciju noteikšanai. Datu apstrāde tika veikta, izmantojot datorprogrammas IBM SPSS v.21. Darba rezultātā noskaidrots, ka divu un vairāku galvas smadzeņu metastāžu ķirurģiska evakuācija ļauj pagarināt dzīvildzi un saglabāt pacienta funkcionālo stāvokli noteiktu laika intervālu pēc operācijas. Labāki divu un vairāku cerebrālu metastāžu ķirurģiskas ārstēšanas rezultāti iegūti pacientu grupai ar 2–3 metastāzēm pēc radikālas un totālas visu diagnosticēto mezglu evakuācijas. Statistiski nozīmīga ietekme uz labāku dzīvildzes prognozi postoperatīvi ir šādiem faktoriem: metastāžu skaitam, radikālai metastāžu evakuācijai, pirmsoperācijas KPS un RPA klases rādītājiem. Dzīvildzes prognoze pacientiem ar oligometastāzēm (mediānā dzīvildze – 5,5 mēneši) ir 2,66 reizes garāka, salīdzinot ar pacientiem, kuriem ir multiplas cerebrālās metastāzes (mediānā dzīvildze – 2,06 mēneši) (p < 0,05). Kompleksas terapijas (WBRT vai WBRT un ķīmijterapijas) pielietojums parciālas smadzeņu metastāžu evakuācijas gadījumā dod nelielu dzīvildzes pagarinājumu salīdzinājumā ar daļēju, tikai ķirurģisku metastāžu evakuāciju. Pirmo 16 Latvijā radioķirurģiski ārstēto pacientu izvērtējums, kuriem bija nelielas (līdz 3 cm diametrā) cerebrālās metastāzes, uzrāda pozitīvus rezultātus, kuri prasa tālākus pētījumus un analīzi. Histoloģiskā materiāla ģenētiskajā analīzē (11 novērojumos no 40) tika konstatētas klīniski nozīmīgas TP53 gēna mutācijas. Statistiski nozīmīga ietekme starp pēcoperācijas dzīvildzi un TP 53 gēna mutācijām pētījumā netika konstatēta. Veiktā darba rezultātā tika izstrādātas praktiskās rekomendācijas ārstēšanas taktikas izvēlei slimniekam ar divām un vairākām cerebrālām metastāzēm.Promocijas darbs veikts ar Eiropas sociālā fonda projekta “Atbalsts doktorantiem studiju programmas apguvei un zinātniskā grāda ieguvei Rīgas Stradiņa universitātē” finansiālu atbalstu

Divu un vairāku cerebrālu metastāžu kompleksas ārstēšanas iespējas. Promocijas darba kopsavilkums

Doctoral Thesis was carried out at the clinical basis of Rīga Stradiņš University Department of Neurology and Neurosurgery – Riga East Clinical University Hospital (RECUH) Clinical Centre “Gaiļezers” (Heads of Department Dr. K. Bicāns, Professor J. Ozoliņš ) – in cooperation with Latvian Oncology Centre Clinic of Therapeutic Radiology and Medical Physics (Head of Clinics, Ph. D. , Assistant Professor O. Utehina) and Radiation Therapy Department (Head Z. Liepa). Diagnostic radiology and control of therapy was mostly performed at the clinical base of Radiology Department – RECUH Clinical Centre “Gaiļezers” (Head Professor G. Krūmiņa). Genetic analysis of evacuated cerebral metastases was performed in collaboration with Rīga Stradiņš University Institute of Oncology (Head Professor E. Miklaševičs). Defence: at the public session of the Doctoral Committee of Medicine on 10 June 2015 at 15.00 in Hippocrates Lecture Theatre, 16 Dzirciema Street, Rīga Stradiņš University.The title of the doctoral thesis is Combined Therapy Options of One or More Cerebral Metastases . The doctoral theses is devoted to one of the most topical problems in the field of modern neurosurgery and oncology – treatment tactics in case of cerebral cancer metastases and possibilities to improve treatment outcomes using most recent available resources. Cerebral metastases are the most common type of intracranial tumors. As a result of improved extracranial pathology therapy outcomes and increased availability of neuroradiology examinations, the number of diagnosed cerebral metastases is tended to be increased. Now, also in Latvia, it is possible to use most recent therapeutic methods for the treatment of cerebral metastases: surgical resection, stereotactic radiosurgery, whole brain radiotherapy (WBRT) and chemotherapy. For patients with one cerebral metastasis, treatment tactics are usually standardized and is radical as possible including surgery and administration of complex therapy. In patients with two or more cerebral metastases clear indications for surgical and complex therapy cannot yet be found. The aim of our study was to analyse and compare possibilities and results of surgical and combined treatment in cases with two or more cerebral metastases and to evaluate first results of radiosurgical cerebral metastases treatment in Latvia. In the retrospective study were analysed data of 40 surgically-treated patients (including 14 patients receiving complex treatment in postoperative period) and first 16 patients in Latvia who received stereotactic radiosurgery therapy and radiotherapy; patients were treated at clinical centres of Riga East Clinical University Hospital during the time period from year 2005 to 2012. The therapy outcomes and survival in relation to clinical and radiological criteria and applied tactics for the treatment were evaluated, as well as analysis of genetic material of the evacuated cerebral metastases for determination of clinically significant mutation of gene TP53. A specialized software – IBM SPSS v.21– was used for data processing. As derived at the conclusion of the work the surgical evacuation of two or more cerebral metastases during a specified interval of time following the surgery allows to increase survival time and to maintain patient’s functional status. The best results of the surgical treatment of two or more cerebral metastases were obtained in the group of patients with 2–3 metastases after radical and total evacuation of all diagnosed cancer cerebral metastases. A statistically significant influence to a better prognosis of post-operative survival time show the following factors: number of metastases, radical evacuation of metastases, pre-operative KPS and RPA class indicators. Prognosis of survival in patients with oligometastases (median survival – 5.5 months) is 2.66 times longer than in patients with multiple cerebral metastases (median survival is 2.06 months) (p < 0.05). Administration of complex therapy (WBRT or WBRT and chemotherapy) in case of partial evacuation of cerebral metastases ensures a slightly prolonged survival time in comparison with cases of only partial surgical evacuation of metastases. Assessment of first 16 patients with small cerebral metastases (in diameter up to 3 cm) treated with radiosurgery in Latvia produce positive results requiring further research and analysis. Under genetic analysis of histological material (11 observations out of 40) there were established clinically significant mutations of gene TP53. No statistically significant influence between the post-operative survival ratio and mutations of gene TP53 was established during the study. As a result of the work there were developed practical recommendations on the choice of treatment tactics for patients with two or more cerebral metastases.Doctoral thesis was carried out with a financial support of European Social Fund project “Financial support for doctoral students for acquisition of study program and obtaining of scientific degree qualification at Rīga Stradiņš University”

Biomarkers for Traumatic Brain Injury: Data Standards and Statistical Considerations

Recent biomarker innovations hold potential for transforming diagnosis, prognostic modeling, and precision therapeutic targeting of traumatic brain injury (TBI). However, many biomarkers, including brain imaging, genomics, and proteomics, involve vast quantities of high-throughput and high-content data. Management, curation, analysis, and evidence synthesis of these data are not trivial tasks. In this review, we discuss data management concepts and statistical and data sharing strategies when dealing with biomarker data in the context of TBI research. We propose that application of biomarkers involves three distinct steps-discovery, evaluation, and evidence synthesis. First, complex/big data has to be reduced to useful data elements at the stage of biomarker discovery. Second, inferential statistical approaches must be applied to these biomarker data elements for assessment of biomarker clinical utility and validity. Last, synthesis of relevant research is required to support practice guidelines and enable health decisions informed by the highest quality, up-to-date evidence available. We focus our discussion around recent experiences from the International Traumatic Brain Injury Research (InTBIR) initiative, with a specific focus on four major clinical projects (Transforming Research and Clinical Knowledge in TBI, Collaborative European NeuroTrauma Effectiveness Research in TBI, Collaborative Research on Acute Traumatic Brain Injury in Intensive Care Medicine in Europe, and Approaches and Decisions in Acute Pediatric TBI Trial), which are currently enrolling subjects in North America and Europe. We discuss common data elements, data collection efforts, data-sharing opportunities, and challenges, as well as examine the statistical techniques required to realize successful adoption and use of biomarkers in the clinic as a foundation for precision medicine in TBI

Variation in neurosurgical management of traumatic brain injury: a survey in 68 centers participating in the CENTER-TBI study

BACKGROUND: Neurosurgical management of traumatic brain injury (TBI) is challenging, with only low-quality evidence. We aimed to explore differences in neurosurgical strategies for TBI across Europe. METHODS: A survey was sent to 68 centers participating in the Collaborative European Neurotrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. The questionnaire contained 21 questions, including the decision when to operate (or not) on traumatic acute subdural hematoma (ASDH) and intracerebral hematoma (ICH), and when to perform a decompressive craniectomy (DC) in raised intracranial pressure (ICP). RESULTS: The survey was completed by 68 centers (100%). On average, 10 neurosurgeons work in each trauma center. In all centers, a neurosurgeon was available within 30 min. Forty percent of responders reported a thickness or volume threshold for evacuation of an ASDH. Most responders (78%) decide on a primary DC in evacuating an ASDH during the operation, when swelling is present. For ICH, 3% would perform an evacuation directly to prevent secondary deterioration and 66% only in case of clinical deterioration. Most respondents (91%) reported to consider a DC for refractory high ICP. The reported cut-off ICP for DC in refractory high ICP, however, differed: 60% uses 25 mmHg, 18% 30 mmHg, and 17% 20 mmHg. Treatment strategies varied substantially between regions, specifically for the threshold for ASDH surgery and DC for refractory raised ICP. Also within center variation was present: 31% reported variation within the hospital for inserting an ICP monitor and 43% for evacuating mass lesions. CONCLUSION: Despite a homogeneous organization, considerable practice variation exists of neurosurgical strategies for TBI in Europe. These results provide an incentive for comparative effectiveness research to determine elements of effective neurosurgical care.status: publishe