Trial of decompressive craniectomy for traumatic intracranial hypertension1Dr fakhir Raza
The New England Journal of Medicine, Trial of Decompressive Craniectomy for Traumatic Intracranial Hypertension, Extended Glasgow Outcome Scale (GOS-E), vegetative state, lower severe disability, traumatic brain injury, RESCUEicp,
EBM Is the ability to access, asses and apply the best evidence from systematic research information to daily clinical problems after integrating them with the physician's experience and patient's value.
Trial of decompressive craniectomy for traumatic intracranial hypertension1Dr fakhir Raza
The New England Journal of Medicine, Trial of Decompressive Craniectomy for Traumatic Intracranial Hypertension, Extended Glasgow Outcome Scale (GOS-E), vegetative state, lower severe disability, traumatic brain injury, RESCUEicp,
EBM Is the ability to access, asses and apply the best evidence from systematic research information to daily clinical problems after integrating them with the physician's experience and patient's value.
Ketamine - clinical use in major depression - Mats Lindström - SSAI2017scanFOAM
A talk by Mats Lindström at the 2017 meeting of the Scandinavian Society of Anaestesiology and Intensive Care Medicine.
All of the conference content can be found here: https://scanfoam.org/ssai2017/
Developed in collaboration between scanFOAM, SSAI and SFAI.
Track 6. Technological innovations in biomedical training and practice
Authors: Jesús M Gonçalves, M J Sanchez-Ledesma, P Ruisoto, M Jaramillo, J J Jimenez and J A Juanes
A prospective randomised trial of the optimal dose of mannitol for intra operative Brain relaxation in patients undergoing craniotomy for supratentorial brain tumour : Hyungseok et al.
Journal club :Neurosurgical conference , KKU.
I should this paper to review how they study of the optimum dosage of mannitol in neurosurgical operation.
Ketamine - clinical use in major depression - Mats Lindström - SSAI2017scanFOAM
A talk by Mats Lindström at the 2017 meeting of the Scandinavian Society of Anaestesiology and Intensive Care Medicine.
All of the conference content can be found here: https://scanfoam.org/ssai2017/
Developed in collaboration between scanFOAM, SSAI and SFAI.
Track 6. Technological innovations in biomedical training and practice
Authors: Jesús M Gonçalves, M J Sanchez-Ledesma, P Ruisoto, M Jaramillo, J J Jimenez and J A Juanes
A prospective randomised trial of the optimal dose of mannitol for intra operative Brain relaxation in patients undergoing craniotomy for supratentorial brain tumour : Hyungseok et al.
Journal club :Neurosurgical conference , KKU.
I should this paper to review how they study of the optimum dosage of mannitol in neurosurgical operation.
Definition of hip fracture in elder population, risk factor, medical management.
and evaluating a journal club of article " Spinal Anesthesia or General Anesthesia for Hip Surgery in Older Adults"
The importance of sex and gender in medical researchCoda Change
The importance of sex and gender in medical research.
For many years it was widely assumed that the occurrence and outcome of disease was the same for women and men.
Our understanding was that studies involving only men would be equally relevant for women. In the last two decades however, it has been shown that this assumption is highly prejudice and can have a detrimental impact on the health of women.
It is, therefore, really important to incorporate a sex and gender research lens in to medical research.
First, Kelly makes the important distinction between sex and gender and how this can impact medical diagnosis, treatment and outcomes.
Then, she identifies how the incorporation of sex and gender into research has allowed for advancements across healthcare. Improved accuracy, avoiding misinterpretation, reduced unintentional bias and greater social equity to name a few.
In this presentation, Kelly Thompson refers to case studies to examine the differences in the interpretation of health data when examining through a sex and gender research lens.
The severity of disease, risk factors and treatment effectiveness are just a few of the reasons why this is so important.
Kelly encourages researchers to ensure gender diversity in the research team and to explain how sex and gender are accounted for in research applications moving forward.
From CodaZero Live, tune into this fascinating discussion on the importance of sex and gender in medical research by Kelly Thompson.
Published Research, Flawed, Misleading, Nefarious - Use of Reporting Guidelin...John Hoey
Much published health sciences literature is misleading and biased
Efforts to correct this include use of reporting guidelines- criteria for doing science and reporting the results properly
Also discussion of conflicts of interest - how to report them.
ICN Victoria presents Dr Dashiell Gantner, research fellow at the Monash University in Melbourne. Here he talks about translating ICU research into clinical practice.
MedicalResearch.com: Exclusive Interviews with Medical Research and Health Care Researchers from Major and Specialty Medical Research Journals and Meetings
Clinical trials: quo vadis in the age of covid?Stephen Senn
A discussion of the role of clinical trials in the age of COVID. My contribution to the phastar 2020 life sciences summit https://phastar.com/phastar-life-science-summit
Rhetorical moves and audience considerations in the discussion sections of ra...jodischneider
European Conference on Argumentation talk
Jodi Schneider, Graciela Rosemblat, Shabnam Tafreshi and Halil Kilicoglu “Rhetorical moves and audience considerations in the discussion sections of Randomized Controlled Trials of health interventions” [Conference Panel Presentation], 2nd European Conference on Argumentation: Argumentation and Inference, Fribourg, Switzerland, June 20-23
1 of 3 talks in Jodi Schneider and Sally Jackson, organizers, “Innovations in Reasoning and Arguing about Health ”[Conference Panel], 2nd European Conference on Argumentation: Argumentation and Inference, Fribourg, Switzerland, June 20-23.
Effect of hydrocortisone on development of shock amongDr fakhir Raza
effects of hydrocortisone on development of shock among patients with severe sepsis the HYPRESS Randomized Clinical Trial American Medical Association caring for the critically ill patients Surviving sepsis campaign, to determine weather hydrocortisone therapy in patients with severe sepsis prevents the development of septic shock
Paula Dawson – The Flying Colours ProjectMQ_Library
The Flying Colours Project by Paula Dawson began on 26th of March 2020 in response to the situation caused by the COVID-19 pandemic. The first 60 watercolour works in the series have each been painted with a particular individual or family in mind, imagining what colours would speak to them. The paintings vary in size from 46 x 61 cm and 36 x 51 cm to smaller works measuring 26 x 36 cm. Each painting with its personally chosen pallet has been sent by Australia Post or given in person at the recommended social distancing space. There is a performative element to the series as Paula makes a unique work in her studio each day since the onset of the pandemic.
The extraordinary hologram To Absent Friends, created by Paula Dawson in 1989 was generously donated to Macquarie University by Paula in 2005. At that time To Absent Friends was the largest depth of field hologram in the world, it’s a super dazzling work that is one of a kind on an international scale. Tours on dedicated days and times will be organised for the latter part of this year.
The Flying Colours Project coincides with the 10 year anniversary of launching the landmark exhibition Virtual Encounters: Paula Dawson Holograms at Macquarie University Art Gallery in partnership with Newcastle Region Art Gallery.
Please follow the link to the MUAG website to view Paula’s remarkable series of works in all its variations of pattern, colour and movement.
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
Follow us on: Pinterest
Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
Basavarajeeyam is an important text for ayurvedic physician belonging to andhra pradehs. It is a popular compendium in various parts of our country as well as in andhra pradesh. The content of the text was presented in sanskrit and telugu language (Bilingual). One of the most famous book in ayurvedic pharmaceutics and therapeutics. This book contains 25 chapters called as prakaranas. Many rasaoushadis were explained, pioneer of dhatu druti, nadi pareeksha, mutra pareeksha etc. Belongs to the period of 15-16 century. New diseases like upadamsha, phiranga rogas are explained.
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
Best Ayurvedic medicine for Gas and IndigestionSwastikAyurveda
Here is the updated list of Top Best Ayurvedic medicine for Gas and Indigestion and those are Gas-O-Go Syp for Dyspepsia | Lavizyme Syrup for Acidity | Yumzyme Hepatoprotective Capsules etc
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
263778731218 Abortion Clinic /Pills In Harare ,sisternakatoto
263778731218 Abortion Clinic /Pills In Harare ,ABORTION WOMEN’S CLINIC +27730423979 IN women clinic we believe that every woman should be able to make choices in her pregnancy. Our job is to provide compassionate care, safety,affordable and confidential services. That’s why we have won the trust from all generations of women all over the world. we use non surgical method(Abortion pills) to terminate…Dr.LISA +27730423979women Clinic is committed to providing the highest quality of obstetrical and gynecological care to women of all ages. Our dedicated staff aim to treat each patient and her health concerns with compassion and respect.Our dedicated group ABORTION WOMEN’S CLINIC +27730423979 IN women clinic we believe that every woman should be able to make choices in her pregnancy. Our job is to provide compassionate care, safety,affordable and confidential services. That’s why we have won the trust from all generations of women all over the world. we use non surgical method(Abortion pills) to terminate…Dr.LISA +27730423979women Clinic is committed to providing the highest quality of obstetrical and gynecological care to women of all ages. Our dedicated staff aim to treat each patient and her health concerns with compassion and respect.Our dedicated group of receptionists, nurses, and physicians have worked together as a teamof receptionists, nurses, and physicians have worked together as a team wwww.lisywomensclinic.co.za/
Local Advanced Lung Cancer: Artificial Intelligence, Synergetics, Complex Sys...Oleg Kshivets
Overall life span (LS) was 1671.7±1721.6 days and cumulative 5YS reached 62.4%, 10 years – 50.4%, 20 years – 44.6%. 94 LCP lived more than 5 years without cancer (LS=2958.6±1723.6 days), 22 – more than 10 years (LS=5571±1841.8 days). 67 LCP died because of LC (LS=471.9±344 days). AT significantly improved 5YS (68% vs. 53.7%) (P=0.028 by log-rank test). Cox modeling displayed that 5YS of LCP significantly depended on: N0-N12, T3-4, blood cell circuit, cell ratio factors (ratio between cancer cells-CC and blood cells subpopulations), LC cell dynamics, recalcification time, heparin tolerance, prothrombin index, protein, AT, procedure type (P=0.000-0.031). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and N0-12 (rank=1), thrombocytes/CC (rank=2), segmented neutrophils/CC (3), eosinophils/CC (4), erythrocytes/CC (5), healthy cells/CC (6), lymphocytes/CC (7), stick neutrophils/CC (8), leucocytes/CC (9), monocytes/CC (10). Correct prediction of 5YS was 100% by neural networks computing (error=0.000; area under ROC curve=1.0).
Adv. biopharm. APPLICATION OF PHARMACOKINETICS : TARGETED DRUG DELIVERY SYSTEMSAkankshaAshtankar
MIP 201T & MPH 202T
ADVANCED BIOPHARMACEUTICS & PHARMACOKINETICS : UNIT 5
APPLICATION OF PHARMACOKINETICS : TARGETED DRUG DELIVERY SYSTEMS By - AKANKSHA ASHTANKAR
Basavarajeeyam is a Sreshta Sangraha grantha (Compiled book ), written by Neelkanta kotturu Basavaraja Virachita. It contains 25 Prakaranas, First 24 Chapters related to Rogas& 25th to Rasadravyas.
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
2. MACQUARIE NEUROSURGERY
JOURNAL CLUB
P.J. Hutchinson, A.G. Kolias, I.S. Timofeev, E.A. Corteen, M. Czosnyka, J. Timothy, I. Anderson, D.O. Bulters, A. Belli,
C.A. Eynon, J. Wadley, A.D. Mendelow, P.M. Mitchell, M.H. Wilson, G. Critchley, J. Sahuquillo, A. Unterberg, F. Servadei,
G.M. Teasdale, J.D. Pickard, D.K. Menon, G.D. Murray, and P.J. Kirkpatrick, for the RESCUEicp Trial Collaborators*
Trial of Decompressive Craniectomy for Traumatic
Intracranial Hypertension
The New England Journal of Medicine, Sept 2016, volume 375, issue 12, pp1119-30.
3. Authors
• Chief investigator: Professor Peter Hutchinson, University of Cambridge and
Addenbrooke’s hospital
• 22 co-authors and 211 trial collaborators
• 52 centres in 20 countries
4. Disclosures
• Grant from MRC-NIHR partnership
• Evelyn trust
• Dr. Hutchinson reports grants from NIHR Efficacy and Mechanism Evaluation Programme, during the conduct of the study; grants from NIHR Health Technology Assessment
(HTA) Programme, outside the submitted work; and being a Director of Technicam (manufacturer of a cranial access device). Dr. Hutchinson reports having participated in a
consensus conference on intracranial pressure that was held in Milan on October 5, 2013. The conference was financially supported by Codman (a division of Ethicon Ltd.), with
an unconditional grant, though he reports having received no support.
• Dr. Bulters reports grants from Innovate UK, grants from EU FP7, grants from EPSRC, grants from NIHR, grants from Royal College of Surgeons of Edinburgh, grants from
Wessex Medical Research, grants from Smile for Wessex, grants and personal fees from ReNeuron, personal fees from Portola, personal fees from Johnson and Johnson,
grants from Evgen Pharma, grants from Vasopharm, outside the submitted work.
• Dr. Czosnyka reports personal fees from Cambridge Enterprise Ltd., outside the submitted work.
• Dr. Kolias reports grants from NIHR Efficacy and Mechanism Evaluation Programme, during the conduct of the study; grants from NIHR Health Technology Assessment (HTA)
Programme, grants from NIHR Health Technology Assessment (HTA) Programme, outside the submitted work; and The British Neurosurgical Trainee Research Collaborative,
which he chaired from 2012-15, has been supported with an educational grant from Codman, UK. Dr. Kolias reports having participated in a consensus conference on
intracranial pressure that was held in Milan on October 5, 2013. The conference was financially supported by Codman (a division of Ethicon Ltd.), with an unconditional grant.
• Dr. Mendelow reports non-financial support and other from Newcastle Neurosurgery Foundation Ltd., personal fees from Stryker, personal fees from Draeger, outside the
submitted work; and Director of Newcastle Neurosurgery Foundation Ltd.
• Dr. Menon reports grants and non-financial support from GlaxoSmithKline Ltd, personal fees from Pressura Ltd, personal fees from Calico Ltd, personal fees from Glide Pharma
Ltd, personal fees from Pfizer Ltd, personal fees from Medicxi Ventures (UK) LLP , personal fees from Lantmännen AB , grants from Brainscope Ltd, personal fees from Ornim
Medical, personal fees from Shire Medical, other from IMEC Ltd, grants from National Institute for Health Research UK, outside the submitted work; and help with development
of a protocol for a clinical trial of ciclosporin in TBI sponsored by Neurovive. The project did not come to fruition.
• Dr. Pickard reports grants from NIHR Efficacy and Mechanism Evaluation Programme, during the conduct of the study; grants from NIHR Senior Investigator Award, grants from
NIHR Brain Injury Healthcare Technology Co-operative, grants from NIHR Cambridge Biomedical Research Centre (Brain injury theme), personal fees and non-financial support
from Medtronic , personal fees and non-financial support from Codman (Johnson and Johnson), outside the submitted work; and Director, Medicam and Technicam (no
financial remuneration) .
• Dr. Servadei reports grants and personal fees from Codman Company , grants and personal fees from Finceramica , personal fees from Baxter Company , outside the
submitted work
5. Study Relevance
• At the time of trial design (>10yrs ago)
there were many studies on the role of
decompressive craniectomy in TBI,
with a wide range of outcomes
• Concerns that DC simply increases
the amount of patients in a vegetative
state
• Important to resolve the role of this
treatment for a condition with profound
social and economic consequences
6. Relevance/Originality
• ICP >20mmHg for more than 15min within a 1 hr period, despite optimised first tier therapy.
• Significant decrease in ICP in Sx group; mortality was similar (Sx 19% v. non-Sx 18%);
GOS-E scores at 6 months were worse (p=0.03). Contradictory to the literature at the time.
• Concluded that the findings were unlikely to be due to a shift from survival to vegetative
state (due to similar mortality), but rather that DC changes outcome from favourable to
unfavourable.
7. Relevance/Originality
Criticism
• protocol was not reflective of clinical practice
• high number of exclusions (only 4.5% of screened patients were enrolled)
• significant imbalances in baseline characteristics, esp. fixed pupils
8. Trial Design
• International, multi-centre randomised controlled trial
• Two arm, parallel group study
• Pragmatic
• All hospitals provided acute neuroscience care for severe TBI and had 24
hour neurosurgical service
10. Trial Design
Hypotheses
1. Decompressive craniectomy results in an improvement in the Extended Glasgow
Outcome Score compared to optimal medical treatment
2. Decompressive craniectomy results in an improvement in surrogate endpoint
measures (including specific outcome measures [SF-36 questionnaire], control of
ICP, time in intensive care, and time to discharge from the neurosurgical unit)
compared to optimal medical treatment
11. Trial Design
Outcomes
• Primary outcome is GOS-E score at 6 months
• Secondary outcomes:
- GOS-E at 12 and 24 months (after randomisation)
- Mortality at 6, 12, and 24 months (after randomisation)
- QOL at 6, 12, and 24 months (after randomisation)
- GCS at discharge from hospital
- assessment of ICP control
- time in ICU
- time to discharge from hospital
- health-economic evaluation
• Adverse events will be recorded
12. Trial Design
How to assess ICP control?
- mean ICP (after randomisation)
- number of hours with ICP>25mmHg (after randomisation)
- the intracranial hypertension index 20
- the intracranial hypertension index 25
- cerebral hypoperfusion index
14. Trial Design
Statistical Analysis Plan
• power calculation: 400 patients required for a 15% difference in outcome
(favourable outcome from 45% to 60%) (power 80%, p=0.05)
• modified intention to treat analysis (excluded patients lost to follow up or who
withdrew consent)
• pre-specified that they would pool ‘upper-good recovery’ and ‘lower good
recovery’
• sensitivity analysis- the proportion of patients achieving a ‘favourable’ outcome
(i.e. upper severe disability or better)
• covariate adjustment (age; GCS motor score; pupils; last pre-randomised
Marshall CT class)
20. Results
Primary outcome:
• ordinal analysis based on proportional odds model
• the goodness of fit of this model was tested with a likelihood-ratio test; this was
rejected, indicating a difference in the distribution of the GOS-E scores in the two
groups (at 5% significance level)
• then, as pre-specified, the groups were compared with a chi-squared test
21. Results
Primary outcome:
• ordinal analysis based on proportional odds model
• the goodness of fit of this model was tested with likelihood-ratio test and was rejected,
indicating a difference in the distribution of the GOS-E scores in the two groups (at 5%
significance level)
• then, as pre-specified, the groups were compared with unordered chi-squared test
23. Results
Primary outcome:
For every 100 patients treated with surgery rather than medical therapy, there will be 22
more survivors. Of these:
- 6 will be in a ‘vegetative state’
- 8 will be ‘lower severe disability’
- 8 will be independent at home or better
24. Results
Secondary outcomes:
For every 100 patients treated with surgery rather than medical therapy, there will be 22
more survivors. Of these:
- 5 will be in a ‘vegetative state’
- 4 will be ‘lower severe disability’
- 13 will be independent at home or better
27. Results
Secondary outcomes:
• No difference in time to discharge/death from ICU (median about 12 days for both)
• If death is censored, median time to d/c from ICU is 15 v. 21 days (p=0.01)
• Secondary outcomes pending: 24 month GOS-E; QOL analysis; health-economic analysis
• 37 adverse events were reported in 33 patients (surgical group). 32 complications and
adverse events were reported in 18 patients (medical group).
28. Results
A priori subgroup analysis (separate binary logistic regression models for mortality and for
favourable outcome):
29. Internal Validity
Statistics:
• power calculation was appropriate (80% with p=0.05)
• 15% change in outcome is comparable to the literature
• achieved their recruitment target (400 patients)
Protocol published before trial and it was followed faithfully, except:
• original protocol - hyperventilate to CO2 26-34mmHg; changed to 30-34mmHg
• steroid therapy was in the original protocol; but removed as an option during trial
• initially cooling to 35-36oC was recommend; changed to ‘therapeutic hypothermia’ as an
option
30. Internal Validity
Randomisation:
• 1:1 allocation with permuted blocks of random size
• Stratified by site
• Blocks were not disclosed to ensure concealment
• Central telephone randomisation service
• Randomisation code was not release until patient had reached stage 3 of the protocol
• Baseline characteristics were similar except: history of drug or alcohol abuse
Blinding:
• clinicians were not blinded
• 2 trial team members reviewed the GOS-E questionnaires independently of each other
and were blinded to the group assignment
31. External Validity
• Representative population
• Relevant inclusion/exclusion criteria
• Modified intention to treat
• The treatment protocol is replicable (keeping in mind pragmatic nature of study)
• Choice of craniectomy technique is replicable
• 12 month follow up and clinically relevant outcomes
• No cranioplasty data
32. Guidelines for the Management of Severe Traumatic Brain Injury brain trauma foundation
2007: 2016:
External validity- 20 or 25?
33. Discussion
• Authors’ conclusion:
• At 6 months, DC for severe and refractory intracranial hypertension
after TBI resulted in mortality that was 22 percentage points lower
than that with medical management.
• Surgery also was associated with higher rates of vegetative state,
lower severe disability, and upper severe disability than medical
management.
• The rates of moderate disability and good recovery with surgery were
similar to those with medical management.
34. Discussion
• Weaknesses:
• dilution of treatment effect given large crossover (37.2%)
• hypothermia used during trial may be harmful (Eurotherm3235)
• steroid use initially an option during the trial
• clinical teams not blinded
• no data on cranioplasty (esp. complications)
• Overall though:
• Clinically relevant and important study
• Well executed a priori protocol
• Robust internal and external validity
35. Conclusion
• Well-conducted RCT
• DC results in reduced mortality, and can thus be used as a life saving intervention for
refractory raised ICP in TBI. There will be increased number of dependent patients at
6-12 months, as well as increased favourable outcomes
• Trial of DC v. barbiturates.
• In contrast to DECRA: a more generalisable result (less restrictive entry criteria; more
pragmatic approach to intracranial hypertension; more reflective of clinical practice)
• Future studies should look at 1) cranioplasty data and 2) the 37% medical group who
underwent DC
Editor's Notes
Didn’t say RCT as per CONSORT transparency reporting of trials
co-authors mostly from the UK, a few from Western Europe
MRC- medical research council. NIHR- national institute for health research
An RCT would also have the benefit of addressing whether surgery shifts the outcome from death to vegetative state
An RCT would also establish incidence of complications
Possible reasons for the results are that ICP is not the driving factor, ?axonal stretch ?oxygen brain tension ?cerebral haemodynamics ?increased cerebral oedema
Important differences
- ICP 25 rather than 20
1-12 hrs of raised ICP required
after failure of stage 2 rather than stage 1 (though ventriculostomy was stage 1 in DECRA)
mass lesions (evacuated or non-evacuated) were excluded from DECRA, included in RESCUEicp
unilateral DC was not allowed in DECRA
In summary- RESCUEicp is assessing DC as a last-tier treatment. DECRA was assessing early DC for moderate intracranial hypertension
Just a few of the criticisms
In fact, after post-hoc adjustment for pupil reactivity, the harmful effect of DC was eliminated
18% of the non-surgical group underwent DC
Pragmatic, focus on outcomes rather than mechanistic pathways. Tests effectiveness in clinical practice. Good at guidance current practice but not necessarily the best at isolating a single treatment effect. For example, not specifying when patient’s had to have CT scans, or whether or not to use mild hypothermia, or what hyperosmolar agents to use etc.
Published in Acta Neurochirurgica Supplement 2006
Pre-specified inclusion/exclusion, protocol, statistical analysis plan, and outcome measures (fundamental to a randomised trial)
The principal hypothesis for the RESCUEicp study is that the application of decompressive craniectomy to TBI patients with raised ICP refractory to medical treatment results in improved outcome.
QOL measured using the 36-item short form health survey (10-item in children)
(the number of end-hourly measures of intracranial pressure of >20 mm Hg divided by the total number of measurements, multiplied by 100)
(the number of end-hourly measures of cerebral perfusion pressure of <60 mm Hg divided by the total number of measurements, multiplied by 100).
Decompressive craniectomy could be performed later if a patient deteriorates, and barbiturates may be given if the patient deteriorates after craniectomy
These were at clinician’s discretion. (the interest of the patient always prevails of the interest of science and society).
powered to account for a loss to follow-up of 15%
ITT ‘once randomised, always analysed’
One of the main reasons to use ITT is to account for missing outcomes, (can use last outcome carried forward for example)
whilst there is concern over “modified ITT” in the literature, it seems this is due to studies not reporting what they are excluding. ?Less bias than post-randomisation deviations in other trials
perhaps they did this to avoid the possible dilution efficacy of a treatment (a criticism of ITT in drug trials)
groups pooled as expected to be too few patients to analyse these groups individually
Validated global outcome scale assessing function in multiple domains, common in TBI trials
Dichotomisation usually occurs 2-4 as unfavourable, in this paper it is 2-3, due to anticipated high number of poor outcomes (a priori). similar approach in some other trials
4 (upper severe disability) means patient is independent at home but need assistance to travel, shopping etc. whereas 3 need assistance at home or live in a care facility
CT - haematoma, contusion, swelling, herniation or compressed basal cisterns
mass lesion evacuation different to DECRA
heterogenous population (patients with mass lesion v. patients with diffuse injury)
Recruitment from 2004 to 2014
71% of patients from the UK
Largest proportion excluded due to normal ICP (30%)
12% had a primary DC
Not unreasonable exclusion overall (though reason not given 153, compare only 3 in eurotherm)
12 month analysis: 6% and 12% lost to follow up
pupil abnormality = unreactive pupils or anisocoria
Baseline characteristics were similar for the two groups except for history of drug or alcohol abuse, which was significantly different
Note high proportion of male; 50% has poor motor GCS score; 40% had extracranial injury
Marshall classification for CT was used - majority had diffuse injury, note that 20% had mass lesion
no significant differences in pre-randomisation treatments
very high number of patients in medical group underwent DC, smaller number underwent barbiturate therapy in surgical group
information on DC was only collected in the surgical group
in order to describe the way in which the two groups GOS-E scores differed
so 22% decrease in death
another way of looking at it: no difference in best outcomes (i.e. lower 3 usually means patients return to work)
Contrast to DECRA in which mortality was essentially the same, it would seem the increase in unfavourable outcome is due to decreased mortality
Outcome of “extra survivors”
how do you present to patients. More likely to live…
?at 12 months less than half will end up in a care facility
?at 6 months more than half will be in a care facility
the number of end-hourly measures of intracranial pressure of >20 mm Hg divided by the total number of measurements, multiplied by 100
the number of end-hourly measures of cerebral perfusion pressure of <60 mm Hg divided by the total number of measurements, multiplied by 100
significantly shorter d/c from ICU in surgical group
significantly less medical patients had complications
Separate binary logistic regression models were fitted for mortality and for favourable outcome, with an interaction term included in the model to assess any subgroup effect. 12 interaction terms evaluated
no subgroup effect (bordeline for age, p=0.025)
Other TBI studies use 10%, DECRA 20%, eurotherm 7%
Steroid stopped due to evidence of harm that emerged during trial, same with hypocarbia
hypothermia changed due to lack of evidence and pragmatic nature of trial
The objective of stratified randomization is to ensure balance of the treatment groups with respect to the various combinations of the prognostic variables. if lots of sites with not many patients, doesn’t work well
Overall seems rigorous
3) intention to treat, more reliable as it accounts for real-work drop-out, non-compliance etc.
6) 6 month follow up what GOS-E was designed for; 12 month reasonable for assessing disposition
7) biggest criticism in generalisability is the lack of cranioplasty data
DECRA used this evidence, although remember this evidence is not for ‘DC at 20, it’s a variety of treatment options for different papers’ . New Data says 22
25 probably reasonable choice, not well justified in background of rescueICP though
eurotherm showed worse outcome in hypothermia group, but more stage 3 treatments in non hypothermia group
hypothermia and steroid use not criticisms of the trial, but must be remembered
2) How to explain to a family member decision making
3) Perhaps barbiturates should be stage 3, then DC as stage 4. Do not know without data on the 37%
Finally- RescueASDH is underway, weather to replace bone flap or not.