The answer is 17 years, what is the question: understanding time lags in translational research

With NO leadership in stroke, you better postpone your stroke for decades!

The answer is 17 years, what is the question: understanding time lags in translational research

Zoë Slote Morris,¹ Steven Wooding,² and Jonathan Grant²

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See editorial "Knowledge, lost in translation" in volume 104 on page 487.

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Abstract

This study aimed to review the literature describing and quantifying time lags in the health research translation process. Papers were included in the review if they quantified time lags in the development of health interventions. The study identified 23 papers. Few were comparable as different studies use different measures, of different things, at different time points. We concluded that the current state of knowledge of time lags is of limited use to those responsible for R&D and knowledge transfer who face difficulties in knowing what they should or can do to reduce time lags. This effectively ‘blindfolds’ investment decisions and risks wasting effort. The study concludes that understanding lags first requires agreeing models, definitions and measures, which can be applied in practice. A second task would be to develop a process by which to gather these data.

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Introduction

Timely realization of the benefits of expensive medical research is an international concern attracting considerable policy effort around ‘translation’.^1,2 Policy interventions to improve translation respond to a vast empirical literature on the difficulties of getting research across research phases and into practice.^3–11

Both literature and policy tend to assume that speedy translation of research into practice is a good thing. Delays are seen as a waste of scarce resources and a sacrifice of potential patient benefit.¹² Although some lag will be necessary to ensure the safety and efficacy of new interventions or advances, in essence we should aim to optimize lags. One recent study (of which JG and SW were co-authors) estimating the economic benefit of cardiovascular disease (CVD) research in the UK between 1975 and 2005, found an internal rate of return (IRR) of CVD research of 39%.¹³ In other words, a £1.00 investment in public/charitable CVD research produced a stream of benefits equivalent to earning £0.39 per year in perpetuity. Of this, 9% was attributable to the benefit from health improvements, which is the focus of this paper. (The remaining 30% arise from ‘spillovers’ benefiting the wider economy.) This level of benefit was calculated using an estimated lag of 17 years. Varying the lag time from 10 to 25 years produced rates of return of 13% and 6%, respectively, illustrating that shortening the lag between bench and bedside improves the overall benefit of cardiovascular research. What is notable is that all the above calculations depended upon an estimated time lag; estimated because, despite longstanding concerns about them,¹⁴ time lags in health research are little understood.

It is frequently stated that it takes an average of 17 years for research evidence to reach clinical practice.^1,3,15 Balas and Bohen,¹⁶ Grant¹⁷ and Wratschko¹⁸ all estimated a time lag of 17 years measuring different points of the process. Such convergence around an ‘average’ time lag of 17 years hides complexities that are relevant to policy and practice which would benefit from greater understanding.¹³

Despite longstanding concerns about delays in getting research into practice, the literature on time lags seems surprisingly under-developed. To help address this gap, this paper aims to synthesize existing knowledge and to offer a conceptual model that can be used to standardize measurement and thus help to quantify lags in future. This would allow efforts to reduce lags to be focused on areas of particular concern or value, or on areas where interventions might be expected to have best effect. It would also provide the potential for evaluating the cost-effectiveness of translation interventions if their impact on lags can be measured. The aim was to overlay empirical lag data onto the conceptual model of translational research to provide an overview of estimated time lags and where they occur. The first part of the paper explores conceptual models of the translation pipeline in order to provide context. The second part of the paper presents a review of the literature on time lags to present current estimates and issues. This leads to a discussion on the current state of understanding about time lags and considers the implications for future practice and policy.

More at link.

Seven Strategies to Integrate Equity within Translational Research in Neurology

 FYI.

Seven Strategies to Integrate Equity within Translational Research in Neurology

Karlo J. Lizarraga MD, MS, Tirisham Gyang MD, Richard T. Benson MD, PhD, Gretchen L. Birbeck MD, MPH, DTMH, Karen C. Johnston MD, MS, Walter Royal III MD, Ralph L. Sacco MD, MS, Benjamin Segal MD, Barbara G. Vickrey MD, MPH, Robert C. Griggs MD, Robert G. Holloway MD, MPH

First published: 25 January 2024

https://doi.org/10.1002/ana.26873

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Abstract

The rapidly accelerating translation of biomedical advances is leading to revolutionary therapies that are often inaccessible to historically marginalized populations. We identified and synthesized recent guidelines and statements to propose 7 strategies to integrate equity within translational research in neurology: (1) learn history; (2) learn about upstream forces; (3) diversify and liberate; (4) change narratives and adopt best communication practices; (5) study social drivers of health and lived experiences; (6) leverage health technologies; and (7) build, sustain, and lead culturally humble teams. We propose that equity should be a major goal of translational research, equally important as safety and efficacy. ANN NEUROL 2024

The pace of translational biomedical and technological advances to treat neurological conditions has been astonishing. Life-changing and curative therapies are now available for conditions previously considered incapacitating and lethal. Regrettably, the burden of neurological disease continues to increase as these therapies are often inaccessible to people historically marginalized due to their race, ethnicity, age, sex, gender, culture, or abilities.^1-3 Structural and systemic inequities that exist at upstream sociopolitical and economic levels have also shaped, infiltrated, and compromised the scientific rigor and integrity prioritized by the translational research enterprise in neurology. Translational research grows from preclinical study design to clinical trials to therapy dissemination and implementation. In a similar fashion, avoidable research inequities begin at the design phase, and inadvertently grow to become health care disparities when reaching the dissemination and implementation phases (Fig 1). Inequitable research environments further facilitate this process, which could at least partially explain why health care disparities continue to grow despite significant efforts at the dissemination and implementation phases. In this article, we synthesized recent guidelines and statements to propose 7 actionable strategies to integrate equity within translational research in neurology (Table 1). We use race and ethnicity as the main examples, but these strategies could be applicable to other axes of diversity in an intersectional manner.

FIGURE 1

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Schematic representation of equity, safety, and efficacy during translational research and health care. Equity is considered a major goal of health care, and it is usually addressed after implementation and dissemination of therapies developed during translational research. Safety and efficacy are considered major goals of translational research, and they are usually achieved through scientific rigor and integrity during earlier phases of translational research. Systemic and structural inequities affect all phases of translational research, and they could exacerbate existing health care disparities. Thus, equity could also be considered a major goal of translational research, equally important as safety and efficacy. (Adapted from the National Center for Advancing Translational Sciences website: https://ncats.nih.gov/translation/spectrum.)

Table 1. Seven Strategies to Integrate Equity within Translational Research in Neurology

Strategies	Recommendations
1. Learn history	–Learn about craniometry studies –Learn about “race corrections”
2. Learn about upstream forces	–Learn about the cost of translational research –Learn how research funding areas are prioritized in the United States and advocate for support for research to inform and drive health policies that reduce health disparities –Consider, validate, and promote potentially less expensive research methods
3. Diversify and liberate	–Be inclusive, authentic, transparent, deliberate, and accountable –Move from ethnographic authority to shared power and practices that prioritize science –Share roles of researcher and research participant –Include an “equity focus” or an “equity and implementation plan” during study design
4. Change narratives and adopt best communication practices	–Use a culturally humble communication style –Spell names correctly –Ask for correct name pronunciations –Ask for correct pronouns –Use language that promotes equity
5. Study social drivers of health and lived experiences	–Consider measuring and analyzing relevant social drivers of health –Consider using qualitative interviews or predefined scales to measure and analyze the lived experiences of racism, perceived discrimination, and trust in research –Consider how social oppression has shaped our identities as researchers and research participants
6. Leverage health technologies	–Consider innovative and accessible health technologies –Monitor for and prevent unintended consequences of technology dissemination, including exacerbation of existing inequities
7. Build, sustain, and lead culturally humble teams	–Welcome everyone as a potential team member –Measure and train yourself, and your team members, in implicit bias and shared leadership skills –Consider participating and contributing to programs that specifically address workforce diversity

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A translational roadmap for transcranial magnetic and direct current stimulation in stroke rehabilitation: Consensus- based core recommendations from the third stroke recovery and rehabilitation roundtable

Thiis 'expert' panel totally missed the only goal in stroke: 100% RECOVERY! With stroke medical 'professionals' not even trying for the right goals, stroke survivors will be forever screwed!

 A translational roadmap for transcranial magnetic and direct current stimulation
in stroke rehabilitation: Consensus-based core recommendations from the
third stroke recovery and rehabilitation roundtable

https://doi.org/10.1177/17474930231203982
International Journal of Stroke
1 –13
© 2023 World Stroke Organization
Article reuse guidelines:
sagepub.com/journals-permissions
DOI: 10.1177/17474930231203982
journals.sagepub.com/home/wso
International Journal of Stroke, 00(0)
A translational roadmap for transcranial
magnetic and direct current stimulation
in stroke rehabilitation: Consensus-
based core recommendations from the
third stroke recovery and rehabilitation
roundtable
Jodi D Edwards1,2 , Adan Ulises Dominguez-Vargas3 ,
Charlotte Rosso4
, Meret Branscheidt5
, Lisa Sheehy6
,
Fanny Quandt7 , Simon A Zamora5
, Melanie K Fleming8
,
Valentina Azzollini9
, Ronan A Mooney10
, Charlotte J Stagg8
,
Chiristian Gerloff 7 , Simone Rossi11
, Leonardo G Cohen9
,
Pablo Celnik 10
, Michael A Nitsche12
, Cathrin M Buetefisch13
and Numa Dancause3

Abstract

Background and Aims:  

The purpose of this Third Stroke Recovery and Rehabilitation Roundtable (SRRR3) was
to develop consensus recommendations to address outstanding barriers for the translation of preclinical and clinical research using the non-invasive brain stimulation (NIBS) techniques Transcranial Magnetic Stimulation (TMS) and Transcranial Direct Current Stimulation (tDCS) and provide a roadmap for the integration of these techniques into clinical practice.
Methods: International NIBS and stroke recovery experts (N = 18) contributed to the consensus process. Using a nominal group technique, recommendations were reached via a five-stage process, involving a thematic survey, two priority ranking surveys, a literature review and an in-person meeting.
 

Results and Conclusions:  

Results of our consensus process yielded five key evidence-based and feasibility barriers for
the translation of preclinical and clinical NIBS research, which were formulated into five core consensus recommendations. Recommendations highlight an urgent need for (1) increased understanding of NIBS mechanisms, (2) improved methodological rigor in both preclinical and clinical NIBS studies, (3) standardization of outcome measures, (4) increased clinical relevance in preclinical animal models, and (5) greater optimization and individualization of NIBS protocols.
To facilitate the implementation of these recommendations, the expert panel developed a new SRRR3 Unified NIBS Research Checklist. These recommendations represent a translational pathway for the use of NIBS in stroke rehabilitation research and practice.
1University of Ottawa Heart Institute, Ottawa, ON, Canada
2School of Epidemiology and Public Health, University of Ottawa, Ottawa, ON, Canada
3Université de Montréal, Montréal, QC, Canada
4Institut du Cerveau et de la Moelle épinière, Paris, France
5Cereneo Center for Neurology and Rehabilitation, Vitznau, Switzerland
6Bruyére Research Institute, Ottawa, ON, Canada
7University Medical Center Hamburg-Eppendorf, Hamburg, Germany
8University of Oxford, Oxford, UK
9National Institutes of Health, Bethesda, MD, USA
10 Johns Hopkins University, Baltimore, MD, USA
11 University of Siena, Siena, Italy
12 Leibniz Research Center for Working Environment and Human Factors, Dortmund, Germany
13 Emory University, Atlanta, GA, USA
This contribution, first published in International Journal of Stroke, is being co-published in the following journals: Neurorehabilitation and Neural Repair.

Stroke patients may benefit from brain stimulation

 

In here is one that is non-invasive, no surgery. Why was this research done with all this earlier stuff? Your mentors and senior researchers incompetently didn't know about it?

• deep brain stimulation (12 posts to July 2015)

Stroke patients may benefit from brain stimulation

At a Glance

• In a small trial, deep brain stimulation plus physical therapy helped improve upper limb function in some patients who had impaired movement after a stroke.
• The effectiveness of the approach would need to be confirmed in larger trials before it could be considered for broader use.

A single DBS lead is implanted into the cerebellum, with nerve fibers extending from the implant region through the thalamus and into the motor cortex. Cleveland Clinic Foundation

Stroke is a leading cause of death and serious long-term disability in the United States. About half of those who survive a stroke are left with ongoing impairments that affect their everyday activities, such as walking or lifting objects. Physical therapy can help to improve movement and reduce symptoms. But its benefits often level off about a year following the stroke.

Scientists have been exploring the possibility of encouraging the brain to form new connections between nerve cells by using electrical stimulation. The approach, called deep brain stimulation, delivers constant electrical stimulation to a particular brain region through a surgically implanted thin wire, or electrode.

A research team co-led by Drs. André Machado and Kenneth B. Baker of the Cleveland Clinic targeted a brain region called the dentate nucleus. It lies within the brain’s cerebellum, in the lower back of the head. The cerebellum is known to play a role in coordinating muscle movements. Decades of animal studies have shown that the dentate nucleus is a key connector that helps link the cerebellum to the motor cortex, which controls voluntary movements.

In a phase 1 clinical trial, the team enrolled 12 people who had moderate to severe impairment of their upper limbs one to three years after a stroke. At the start of the study, participants engaged in a month of physical therapy twice a week to rule out possible recovery based on physical therapy alone. Each then underwent surgery to insert the electrode in the brain’s dentate nucleus. After a recovery period, physical therapy continued, and deep brain stimulation was delivered continuously for four to eight months. Results were reported in Nature Medicine on August 14, 2023.

The researchers found that their technique of combining deep brain stimulation with physical therapy was safe. No serious adverse events or device failures were noted. Nine of the 12 participants had improved motor function after the treatment. These improvements continued even after stimulation was turned off.

Importantly, the length of time since a patient’s stroke did not seem to affect the potential for improvement. But the level of motor function in the hand did seem relevant to recovery. Participants who had retained some level of motor function in the hand had clinically significant improvement. Those with a low level of motor function showed only minor gains.

“The results of the study found that deep brain stimulation, paired with physical therapy, improved movement in patients who were more than a year out from their stroke and whose motor improvements had largely plateaued,” Baker says. “This tells us the research warrants further investigation in larger patient samples.”

Deep Brain Stimulation Promising in Post-Stroke Recovery

In here is one that is non-invasive, no surgery. Why was this research done with all this earlier stuff? Your mentors and senior researchers incompetently didn't know about it?

• deep brain stimulation (10 posts to July 2015)

 

Deep Brain Stimulation Promising in Post-Stroke Recovery

An early-stage clinical trial has shown that deep brain stimulation (DBS) applied to the cerebellum may aid the recovery of upper limb function after stroke.

Researchers studied 12 people with moderate to severe upper extremity impairment after stroke who received DBS to the dentate nucleus (DN) of the cerebellum together with rehabilitation and found that 75% of the participants had meaningful response in regaining some function of their paralyzed arms.

PET revealed significant increments in brain metabolism around the part of the brain affected by the stroke.

"Our findings support the safety and feasibility of deep brain stimulation to the cerebellar dentate nucleus as a promising tool for modulation of late-stage neuroplasticity for functional recovery," the authors write.

"The results of the phase I study are promising; but more research is needed. The next step is a phase II clinical trial that is already enrolling patients at Cleveland Clinic," said senior author André Machado, MD, PhD, chairman, Neurological Institute and Charles and Christine Carroll Family Endowed Chair in Functional Neurosurgery, Cleveland Clinic. 

The study was published online August 14 in Nature Medicine.

Extending the Neuroplasticity Window

Machado patented the DBS method in stroke recovery, a release from Cleveland Clinic notes. Boston Scientific owns a license to those patents and provided the Vercise DBS systems used in this trial. In 2010, Cleveland Clinic Innovations established Enspire DBS Therapy, Inc, a Cleveland Clinic portfolio company, and is commercializing technology developed at Cleveland Clinic to commercialize the method and it co-funded the study. Machado holds stock options and equity ownership rights with Enspire and serves as the chief scientific officer.

"Stroke is a leading cause of physical disability in the US and around the world; and while physical and occupational therapy work and improve function, about 50% of patients maintain severe levels of disability for life," Machado said.

Neuroplasticity is a "well-documented phenomenon that is associated with gradual spontaneous or therapy-driven improvements in post-stroke motor function," the authors write. But the extent of recovery "varies considerably across individuals" and depends on a variety of factors, the authors write.

"Harnessing the potential of neuroplasticity and modulating its extent and timing remains a major frontier in medicine with vast upside and has been the focus of our group," they continue.

The researchers proposed a new surgical approach for "extending the degree and temporal window of neuroplasticity after ischemic and traumatic insults to the brain."

This approach involves continuous stimulation of the cerebellar DN to "modulate neural activity and ipsilesional cortical excitability through activation of the robust, endogenous dentatothalamocortical pathway."

Machado explained that cerebellar DN "promotes reorganization of the cerebral cortex around the area affected by a stroke and increases the activity levels and metabolism of the cerebral cortex." It also promotes new synapses and the expression of long-term potentiation, a neuroplasticity process.

After over one decade of preclinical studies, the researchers applied this approach to humans for the first time, with the primary goal of determining whether cerebellar DBS, in combination with rehabilitation, is safe and feasible for post-stroke motor deficits.

To do so, they conducted the Electrical Stimulation of the Dentate Nucleus for Upper Extremity Hemiparesis Due to Ischemic Stroke (EDEN) study, focusing on 12 individuals (mean age, 57.4 ± 6.5 years; mean Upper-Extremity Fugl-Meyer Assessment [FM-UE] score, 22.9 ± 6.2 points) with chronic moderate to severe hemiparesis of the upper extremity due to a unilateral middle cerebral artery stroke that took place between 12 and 36 months prior.

Each participant underwent DBS surgery. After discharge and recovery from the surgery, they had 3 months of rehabilitation before the device was turned on and then 4-8 months of rehabilitation combined with DBS. They continued with rehabilitation after discontinuation of stimulation treatment.

Translational Potential

The researchers evaluated changes in motor impairment and function during five key intervals. 

• Pre-surgery to post-surgery
• Rehab only (no DBS) 
• Experimental DBS plus rehab phase
• 2-month rehab-carryover phase in the absence of DBS 
• Long-term follow-up: 10 months after termination of the experimental treatment phase

In addition, they used PET imaging to characterize metabolic changes across ipsilateral perilesional cortex before and after the DBS plus rehab phase, with the DBS turned off.

From pre- to post-surgery, there was a median 0.5-point decrease in FM-UE score, which, although not deemed significant, "supported the safety of the procedure."

There was a "modest" three-point median improvement across the pre-stimulation, rehab-only phase (P = .004). After that, an additional seven-point improvement was observed, when rehabilitation was combined with DN-DBS (P = .0005).

The gain found during the DBS plus rehab phase was most pronounced in participants who entered the study with some distal preservation of motor function compared with those who entered without distal preservation (P = .007).

During the 2-month, rehab-carryover phase (continued rehabilitation as DBS was weaned by weekly 25% amplitude reductions over the first month and then off during the second month), no further change in FM-UE was observed.

The median FM-UE score for the full cohort also remained unchanged at the end of the long-term follow-up phase, "supporting the durability of the previously realized treatment-related gains," the authors report.

Moreover, the "robust functional gains were directly correlated with cortical reorganization evidenced by increased ipsilesional metabolism," they add.

Participants experienced no device failures and no study-related serious adverse events throughout the trial.

"This emerging intervention has shown translational potential to modulate the magnitude of neuroplastic reorganization toward recovery of function and to extend its time window to late phases of disability," they conclude.

Brooks Gross, PhD, program director, National Institute of Neurological Disorders and Stroke (NINDS), agreed. "The safety and feasibility data from this early study, combined with the potential symptom improvements, certainly support the need for additional, larger trials to see if cerebellar DBS is indeed a potential treatment for post-stroke motor impairment," he stated in a news release.

'Exciting Data'

Commenting for Medscape Medical News, Steven Cramer, MD, MSc, Susan and David Wilstein Endowed Chair in Rehabilitation Medicine and professor, Department of Neurology, David Geffen School of Medicine at UCLA, noted that patients with post-stroke disability "have limited options in 2023, in terms of therapies to boost stroke recovery."

This study "provides exciting data on the safety and clinical efficacy of cerebellar deep brain stimulation, along with favorable PET biomarker data." But, as this is a "relatively small study with no control arm, this approach should now proceed to testing in a phase II controlled clinical trial," said Cramer, who is also the medical director of research at the California Rehabilitation Institute in Los Angeles and was not involved with the current study.

This study was supported by the National Institutes of Health Brain Research Through Advancing Innovative Neurotechnologies Initiative and by Enspire DBS, a spin-off company of Cleveland Clinic. Machado serves as chief medical officer and chair of the Scientific Advisory Board for Enspire DBS Therapy and is paid with stock options. As the inventor, A.G.M. will receive portions of commercialization and/or Cleveland Clinic Foundation stock revenue and payments through Cleveland Clinic Foundation with fees deducted. The other authors' disclosures are listed on the original paper. Cramer serves as a consultant for AbbVie, Constant Therapeutics, BrainQ, Myomo, MicroTransponder, Neurolutions, Panaxium, NeuExcell, Elevian, Helius, Omniscient, Brainsgate, Nervgen, Battelle, and TRCare.

Nat Med. Published online August 14, 2023. Abstract

I can't find anything on chaos theory for stroke. All because we have fucking failures of stroke associations that can't even create a simple database of stroke research and protocols.

BGU’s( Ben-Gurion University) Negev Lab is bringing stroke rehab into the future

Stroke is tricky. While its effects are well known, the best course of rehabilitation to return to functionality is still very much a mystery. This rehab lab turns translational science for answers.

By EHUD ZION-WALDOKS  

JULY 29, 2021 16:54

 

Dr. Simona Bar-Haim and Dr. Lior Shmuelof in the Negev Lab at ADI Negev

(photo credit: DANI MACHLIS/BGU)

‘The return-to-work rate for people after suffering a stroke has not significantly changed since the 1970s,” says Dr. Simona Bar-Haim, founding director of the Negev Lab at the ADI Negev-Nahalat Eran Rehabilitation Village in southern Israel.

Bar-Haim is not your typical academic. She has one foot firmly in the field, and one foot firmly in the academy as a member of the department of physical therapy in the Faculty of Health Sciences at Ben-Gurion University of the Negev (BGU). She also founded a start-up based on chaos theory to help people walk after suffering a stroke.

“Many people do not recover enough to return to work or to their regular lives,” she says.

What is more, as the population ages and lives longer, there are more and more people suffering strokes and then recovering only partial functionality. In Israel, 17,000-20,000 people a year suffer a stroke.

Stroke is tricky. While its effects are well known, the best course of rehabilitation to return to functionality is still very much a mystery, to which Bar-Haim and Dr. Lior Shmuelof, also of BGU, have devoted themselves to help solve.

Driven by that impetus to help and by her out-of-the-box way of thinking, Bar-Haim recently set up a translational rehabilitation lab at the rehabilitation village. Translational science tries to find solutions for real-world problems. At ADI Negev, the problems arise from the patients themselves, their doctors and caregivers, and the solutions are tested in conjunction with the patients.

There are several theories why stroke recovery has not progressed since the 1970s and the Negev Lab has been working to test them.

“We believe there is a critical period of three to six months after the stroke where recovery is most achievable because of the brain’s plasticity during that time,” says Shmuelof of the Negev Lab, the department of brain and cognitive sciences and the Zlotowski Center for Neuroscience at BGU. “If an animal suffers a stroke, it recovers fully. Why do animals recover, while people do not? One possibility is that an animal is active from the moment it happens. Now, if a person suffers a stroke, they spend the first week to 10 days lying in bed in the hospital, and then they spend a couple of hours a day doing physical therapy that does not translate to the real world.”

To confirm these hypotheses, Shmuelof is partnering with the MRI Imaging Center at Soroka-University Medical Center and researchers Profs. Alon Friedman, Ilan Shelef, Anat Horev and Gal Ben-Arie, with the aim of identifying the neural components associated with brain plasticity after injury.

Shmuelof will then take what he learns from MRI imaging and bring it back to the Negev Lab.

ADI NEGEV-Nahalat Eran is a fully equipped facility in a village setting, with residential care for people with multiple disabilities and complex medical conditions, an intensive care hospital wing for babies and adults, a paramedical center, hydrotherapy pool, special education school, green care farm, and a therapeutic horse stable and petting zoo.

It is set in an ideal and idyllic location. Winding paths run alongside the residents’ cottages. A stable for therapeutic riding anchors one side, while the Negev Lab anchors the other. The atmosphere is calm, quiet, happy and optimistic – a far cry from rehabilitation wards in large hospitals.

The ADI Negev-Nahalat Eran Rehabilitation Village was named in memory of Eran Almog, the late son of Didi and Maj.-Gen. (ret.) Doron Almog.

Fueled by his love for Eran, who was born with severe autism and intellectual disabilities, Doron Almog guided the creation of a residential and rehabilitative complex in Israel’s south, which has since become a home and family for more than 150 children and young adults with severe disabilities and complex medical conditions and provides a host of rehabilitative solutions for individuals from all backgrounds and levels of need.

While care is important, the vision is to provide cutting-edge treatment as well. The first step was the creation of the Negev Lab. Not far in the future, the village will also boast a rehabilitation hospital, which will be the biggest in southern Israel.

“ADI Negev is the ideal place to see what happens when people spend many more hours rehabilitating,” says Shmuelof. “What if they spend three hours a day or five hours a day? Would they recover faster and better? These are the kinds of questions we ask ourselves and have the ability to answer because of this unique lab.”

Existing movement tracking methods are not advanced enough to meet Shmuelof’s needs. Therefore, to track patients’ motion over the course of the day, the Negev Lab is developing methods to track not just walking but also arm movements.

“One of the things we noticed is that arm motion might not be completely impaired, but weakness causes people to compensate in other ways rather than moving their arms to regain functionality,” says Shmuelof.

“Putting a research lab in a rehabilitation village makes a lot of sense,” says Bar-Haim. “There, we can go directly to the residents and ask them what their needs are. We can also test out our technologies, which we make sure are fun and pleasant, on the residents and get their feedback.”

A stroke patient walks (photographer: Negev Lab)

THAT IMMEDIATE feedback appealed to Prof. Ilana Nisky of BGU’s department of biomedical engineering, who has joined Bar-Haim in developing a belt that helps stroke patients improve their walking. She is an expert in haptics, which is the body’s sense of touch. Their project is being funded by the Israel Innovation Authority.

“When you design medical devices, you need to think beyond engineering and understand how they [the patients] will be using the devices,” says Nisky.

“One of the most important elements in walking is being able to feel the ground and knowing where your legs are without looking at them. That ability, which we take for granted, can be damaged by a stroke. So, we are designing a belt that is worn on the person’s skin under their clothes that will massage the person’s waist and help them with their terra sense – the sense of where the ground is and where their legs are,” she explains.

“What is truly groundbreaking in our belt is that it does not need to measure where the legs are relative to the ground. Instead, we rely on an artificial intelligence algorithm that we train on many examples of past walking to guess where the ground and legs should be at a given moment in time, based on a very simple sensor that is placed on the belt and in the center of the body. This way the only thing the person after stroke will need is the belt itself.”

The researchers have already developed a prototype, but in the future each belt will be customized to the individual person’s needs.

“We hope they will use the belt, and that the information it provides to them will be helpful,” Nisky says. “We also hope that if they use it a lot, then perhaps they will eventually be able to walk on their own without it.”

To make sure that they will indeed wear it a lot rather than buy it just to have it collect dust in the closet, the team also works with Ofer Canfi, a designer who graduated from the Bezalel Academy of Arts and Design and the Royal Academy of Arts, London, to make the belt look and feel nice, using advanced manufacturing procedures and hi-tech fabrics.

Nisky notes that now is the ideal moment for such research. Haptic devices have become much more pleasant to use. “It’s like a massage. What’s not to like?” she says, while artificial intelligence has reached the point where it can be harnessed for purposes such as physical therapy.

A future entrepreneurial hub

Another important advantage offered by the Negev Lab is its multidisciplinary nature.

“We have clinicians, clinician-researchers, engineers and programmers, all working together,” says Nisky.

Bar-Haim also envisions the Negev Lab as an entrepreneurial hub, a space where technologies from around the world can be tested and receive feedback from the people who stand to benefit from them.

In fact, this vision is already a reality. The Negev Lab collaborates with Swiss-based Mindmaze, which designs virtual reality and computer simulations. It sends its latest technologies to the lab, where Shmuelof puts them through their paces with patients.

One such program lets the patient control a dolphin on a screen by raising or lowering their arms. It has been a big hit with patients.

“Seeing the dolphin move in response to my arm movements shows me how much I have improved,” one says.

“Using the vest gives me hope that I will return to moving my hand easily,” another says. 

“At the end of a treatment session, I feel like my whole body got into it,” says a third.

“People instinctively understand how to control the dolphin, and they enjoy it,” explains Shmuelof.

“The simulation makes me feel like I’m playing a computer game at home, and I just want to pass level after level,” says a patient.

That is encouraging feedback, because the Negev Lab wants to develop programs that people will actually use.

The rehabilitation hospital

In a welcome development, the ADI Negev-Nahalat Eran Neuro-Orthopedic Rehabilitative Hospital is nearing completion. Thanks to the support of multiple government ministries, JNF-USA and international donors, the hospital is set for completion late this year.

It will have more than 100 beds and will provide unique research opportunities.

“It will also be a unique research hospital, with an ethical and information technology infrastructure that will allow us to study most of the activities that will be carried out there,” says Bar-Haim.

“In other words, a large proportion of what goes on in the hospital will be able to be researched and incorporated into academic studies. That is not the case in most hospitals around the world currently, not even in teaching hospitals.

“Once the hospital is completed, the Negev Lab will move into its new space and become the largest and most advanced lab of its kind in Israel.” 

Bar-Haim and Shmuelof are excited about the opportunities to advance their understanding of how to rehabilitate stroke patients using the knowledge they will gain from researching at the hospital.

“How active was the patient during the day? How well did she sleep? How long did she sit for? Measuring patients’ activity during the day will allow us to better understand how it affects their recovery, and to find ways to increase their activity during rehabilitation,” explains Shmuelof.

“We are already receiving inquiries from around the world about this new lab,” he adds.

The future

While the South has lagged behind the Center in terms of medical and rehabilitative care, Bar-Haim and Doron Almog’s vision does not stop at achieving parity with the Center, but, rather, aims to exceed it.

“We believe that residents of the South deserve the same quality of care as those in every other part of the country, and we believe that we can set the bar higher for rehabilitative care,” says Almog.

“This village was founded on the principle that a person is a person no matter what, and this hospital and research lab are finally starting to realize our full vision. In this place, all people will be provided with the best possible care and loved beyond measure.

“In the age of corona, the importance of the Negev Lab is clearer than ever before. Each and every day, our rehabilitation professionals empower people of all ages, backgrounds, and levels of need, giving them a new lease on life and returning them to their families in good health and renewed spirit.

“But we can expedite this process and make it even more powerful through collaborative translational research. There are so many people hurting right now, and the groundbreaking research being done at the Negev Lab can change the face of rehabilitative care across Israel and around the world.”

“I envision the Negev Lab and the ADI Negev-Nahalat Eran Neuro-Orthopedic Rehabilitative Hospital as the core of the future National Rehabilitative Institute of Israel,” declares Bar-Haim.

The writer is deputy spokesperson, international media at Ben-Gurion University. 

Clinical Trials Coordinator (Fixed Term) - Stroke Research group, Department of Clinical Neurosciences, University of Cambridge

When you apply for this job you can explicitly lay out everything wrong in stroke research. Of course the interviewers will sputter and reject your arguments so be prepared for counter arguments, everything for a response is available in this blog.

Three main problems:

1. Not trying for 100% recovery solutions.

2. Researching recovery predictions.

3. Not doing the translation from research to EXACT REHAB PROTOCOLS.

Clinical Trials Coordinator (Fixed Term) - Stroke Research group, Department of Clinical Neurosciences, University of Cambridge

Clinical Trials Coordinator

Stroke Research group, Department of Clinical Neurosciences, University of Cambridge

We are looking for a Clinical Trials Coordinator to join an internationally renowned stroke research unit in the University of Cambridge and Cambridge University Hospitals NHS Foundation Trust. The successful application will coordinate and recruit to, and follow up, individuals in a variety of clinical stroke studies. They will work as part of a multidisciplinary team. We are looking for someone educated to a degree standard in a science specialty, with experience of working on clinical trials/studies and excellent interpersonal and organisational skills.

The post is funded by the NIHR Clinical Research Network until 1st April 2023. Further funding will be conditional on annual renewal of CRN funding.

Once an offer of employment has been accepted, the successful candidate will be required to undergo a standard Disclosure and Barring Service check. This appointment also requires a Research Passport application.

Click the 'Apply' button below to register an account with our recruitment system (if you have not already) and apply online.

Please ensure that you outline how you match the criteria for the post and why you are applying for this role on the online application form.

Please include details of your referees, including email address and phone number, one of which must be your most recent line manager.

Please quote reference ZE27237 on your application and in any correspondence about this vacancy.

The University actively supports equality, diversity and inclusion and encourages applications from all sections of society.

The University has a responsibility to ensure that all employees are eligible to live and work in the UK.

Further information

• Further Particulars

Apply online

 

 

 

Translational Block in Stroke: A Constructive and “Out-of-the-Box” Reappraisal

 This is so simple, you have NO LEADERSHIP AND NO STRATEGY. You are allowing researchers to willy nilly do whatever they think can get funded.

Translational Block in Stroke: A Constructive and “Out-of-the-Box” Reappraisal

Athanasios Lourbopoulos^1,2,3*, Iordanis Mourouzis¹, Christodoulos Xinaris^4,5, Nefeli Zerva¹, Konstantinos Filippakis¹, Angelos Pavlopoulos¹ and Constantinos Pantos¹

• ¹Department of Pharmacology, Medical School, National and Kapodistrian University of Athens, Athens, Greece
• ²Department of Neurointensive Care Unit, Schoen Klinik Bad Aibling, Bad Aibling, Germany
• ³Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig Maximilian University, Munich, Germany
• ⁴IRCCS – Istituto di Ricerche Farmacologiche ‘Mario Negri’, Centro Anna Maria Astori, Bergamo, Italy
• ⁵University of Nicosia Medical School, Nicosia, Cyprus

Why can we still not translate preclinical research to clinical treatments for acute strokes? Despite > 1000 successful preclinical studies, drugs, and concepts for acute stroke, only two have reached clinical translation. This is the translational block. Yet, we continue to routinely model strokes using almost the same concepts we have used for over 30 years. Methodological improvements and criteria from the last decade have shed some light but have not solved the problem. In this conceptual analysis, we review the current status and reappraise it by thinking “out-of-the-box” and over the edges. As such, we query why other scientific fields have also faced the same translational failures, to find common denominators. In parallel, we query how migraine, multiple sclerosis, and hypothermia in hypoxic encephalopathy have achieved significant translation successes. Should we view ischemic stroke as a “chronic, relapsing, vascular” disease, then secondary prevention strategies are also a successful translation. Finally, based on the lessons learned, we propose how stroke should be modeled, and how preclinical and clinical scientists, editors, grant reviewers, and industry should reconsider their routine way of conducting research. Translational success for stroke treatments may eventually require a bold change with solutions that are outside of the box.

Introduction – The Problem of Translational Failure in Stroke

Stroke remains the third leading cause of death in industrialized countries (Dirnagl et al., 1999). The literature is saturated by >1000 effective preclinical studies in acute stroke research (O’Collins et al., 2006), yet almost none are successfully transferred to the acute clinical routine. This is the well-known translational failure or block in stroke research (Endres et al., 2008).

The “basket” of stroke translational failure so far includes neuroprotective agents (O’Collins et al., 2006), stem cells (Borlongan, 2019), or even novel immunological treatments (Elkins et al., 2017), despite rigorous or/and large preclinical effect sizes. Yet we keep on modeling acute stroke and experimenting using, in most cases, the same concepts based on widely cited models. Is this the right way to continue and progress or do we simply need to critically reassess how we model ischaemic stroke?

The fact is that many pathophysiological principles of stroke were actually discovered in translation (Dirnagl and Endres, 2014). Failed clinical trials for acute stroke were probably based on rather weak preclinical evidence or inappropriate models (Drieu et al., 2020). If we consider stroke a “chronic, relapsing” disease, with multiple repeating small or large ischemic insults, then secondary prevention counts for several successes (Kernan et al., 2014). On the other hand, the differences between preclinical rodent modeling and clinical routine practice in human acute stroke are significant (Corbett et al., 2015). Nevertheless, preclinical research has several translational success stories, such as the case of experimental autoimmune encephalomyelitis (EAE) – multiple sclerosis (MS), migraine, and hypothermia in hypoxic-ischaemic encephalopathy (HIE). In addition, existing recommendation papers and consortiums [e.g., ARRIVE (Kilkenny et al., 2010), STAIR (Corbett et al., 2017), STEPS (Savitz et al., 2011)] have repeatedly proposed pathways to success. However, either few groups worldwide are implementing these guidelines or we are still missing some of the factors that are involved in failure.

Hence, we provide here a critical, interdisciplinary, and revisionary overview of stroke translational failure, taking into consideration lessons from “success stories” and “failed concepts” in neuro-research. We argue that translational failure is also the rule in ischaemia of other organs, such as myocardial infarction. Collectively, we believe that translational failure probably lies in fundamental components and “false” choices in the laboratory and clinical research. If we want to succeed, we need to improve not only the current technical hurdles in contemporary neurosciences, but also the way we put our question into perspective (Kola and Landis, 2004; Duda et al., 2014; Garner, 2014; Alteri and Guizzaro, 2018).

“We can’t solve problems by using the same kind of thinking we used when we created them.”

Albert Einstein (1879–1955)

More at link.