further research required

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'More research is needed': empty cliché or words to live by?

Anyone working in academic science will be familiar with the persistent use of this phrase. But rather than a cliché or cop-out, it could be a valuable motto

I studied science at university, as is required for anyone who wants to be a scientist . Trouble is, at the start of my degree at least, I wasn’t a great student. I’d just moved from the tiny village where I’d grown up, so I was frantically trying to figure out how to be an independent adult in the wider world, let alone a capable neuroscientist. So, when faced with essays, practical reports and other mandatory assignments, I fell back on the centuries-old technique favoured by students the world over: make stuff up in an attempt to sound clever.

I can’t remember most of my wilder claims, but I once stated that Phineas Gage “technically invented the lobotomy ”. This logic no doubt seems profound to a persistently hungover 19-year-old, although I doubt my long-suffering markers saw the funny side.

However, now I’m the one doing the marking, and while all my current students are marvellous individuals with working internet connections and the ability to read this, in previous years I’ve been very reassured by seeing countless students try the same tactics as me, proving I wasn’t some lone dunce amongst geniuses (I’ve since found out this feeling is also very common ).

I’m amazed at my ignorance and arrogance, thinking I could fool experienced scientists that I knew what I was talking about. In turn, I confess I’ve marked some submissions that left me quite stunned with their audacity/cluelessness. For instance, one report on a study into the motion aftereffect (involving measuring the vision in both eyes separately) ended with the very profound-sounding claim that “it is often wrongly believed that the eye that is open is the one we see with”.

For the record, this belief is not wrong. It is far from wrong.

Also, a tip for science students; when asked to critically assess a published study, try to refrain from describing the investigator as “unbelievably stupid”, “clearly an idiot” or “basically a monster”. I’ve seen all these used. Criticism is a key element of modern science, but at least try to keep it professional.

However, some tactics are far more predictable, possibly a result of the more rigid methods and requirements of science. One of the more well-known of these is students ending reports or essays on scientific studies, principles or theories by saying “ more research is needed ”, or some variation thereof.

Countless science students end up using this pseudo-insightful conclusion this at some point, often for good reason. Firstly, it’s invariably correct: you seldom get any scientific study which is both completely comprehensive and conclusive, so there’s always scope for more research. Even something as familiar and established as Einstein’s General Theory of Relativity is still being researched a century later .

Secondly, it implies the student is aware of limitations and the wider gaps in the field, and is also willing/able to criticise more established scientists, but without being specific (or directly insulting) in any way.

The problem is that it’s essentially meaningless. Unless a paper or study claims to answer a specific question once and for all and with absolute certainty, more research will always be needed. Saying “more research is needed” at the end of a science report is like saying “we can be sure Shakespeare wrote some plays” at the end of a literature essay: nobody doubts it, it might sound profound, but it isn’t. Students would be advised to think twice before concluding a submission with it, because you won’t be the first to have done so. It’s a habit that some carry on in to professional science careers .

However, perhaps this advice is too narrow-minded? It’s true that the “more research needed” claim has been co-opted somewhat by proponents and advocates of alternative medicine, whenever a study finds that their chosen remedy doesn’t have any noticeable effects . It’s common for alt-med enthusiasts to state that more research is needed, because they’re convinced there is an effect, it just hasn’t been found yet. Sadly, science doesn’t work that way.

But if you apply it to other contexts and occurrences of modern life, it actually makes a lot more sense. An alarming amount, if anything.

A major newspaper claims something “ causes cancer ”? More research is needed.

An alarmingly orange presidential wannabe makes inflammatory claims about Muslims/immigrants/anyone else? More research is needed .

A Facebook post does the rounds making disturbing claims about privacy changes or anything else? More research is needed .

Reports of giant rats in London? More research needed .

Opinion polls tell you who’s going to win the election? Needed, more research is .

Twitter account shares cool images from history? More research moth*****ker, do you need it?

Alarmist study says common drugs cause dementia? We’re gonna need some more research.

Labels on food say that it’s good for you? Some more research? Don’t mind if I do.

Convinced same-sex marriage will ruin civilisation? Do some more research . Also, grow up.

It seems that reminding yourself and others to do just a little more research before deciding something is a fact would benefit almost everyone in any situation. The only exception seems to be in scientific write-ups, which is the only place where it seems to occur.

Why is this? I don’t know. Continued investigations are required.

Dean Burnett invites you to see first-hand just how much more research he should do by buying his first book The Idiot Brain , all about how ridiculous and fallible the human brain is. Alternatively, just follow him on Twitter, @garwboy .

The Idiot Brain by Dean Burnett (Guardian Faber, £12.99). To order a copy for £7.99, go to bookshop.theguardian.com or call 0330 333 6846. Free UK p&p over £10, online orders only. Phone orders min. p&p of £1.99.

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Identifying Research Gaps to Pursue Innovative Research

This article is an excerpt from a lecture given by my Ph.D. guide, a researcher in public health. She advised us on how to identify research gaps to pursue innovative research in our fields.

What is a Research Gap?

Today we are talking about the research gap: what is it, how to identify it, and how to make use of it so that you can pursue innovative research. Now, how many of you have ever felt you had discovered a new and exciting research question , only to find that it had already been written about? I have experienced this more times than I can count. Graduate studies come with pressure to add new knowledge to the field. We can contribute to the progress and knowledge of humanity. To do this, we need to first learn to identify research gaps in the existing literature.

A research gap is, simply, a topic or area for which missing or insufficient information limits the ability to reach a conclusion for a question. It should not be confused with a research question, however. For example, if we ask the research question of what the healthiest diet for humans is, we would find many studies and possible answers to this question. On the other hand, if we were to ask the research question of what are the effects of antidepressants on pregnant women, we would not find much-existing data. This is a research gap. When we identify a research gap, we identify a direction for potentially new and exciting research.

How to Identify Research Gap?

Considering the volume of existing research, identifying research gaps can seem overwhelming or even impossible. I don’t have time to read every paper published on public health. Similarly, you guys don’t have time to read every paper. So how can you identify a research gap?

There are different techniques in various disciplines, but we can reduce most of them down to a few steps, which are:

• Identify your key motivating issue/question
• Identify key terms associated with this issue
• Review the literature, searching for these key terms and identifying relevant publications
• Review the literature cited by the key publications which you located in the above step
• Identify issues not addressed by  the literature relating to your critical  motivating issue

It is the last step which we all find the most challenging. It can be difficult to figure out what an article is  not  saying. I like to keep a list of notes of biased or inconsistent information. You could also track what authors write as “directions for future research,” which often can point us towards the existing gaps.

Different Types of Research Gaps

Identifying research gaps is an essential step in conducting research, as it helps researchers to refine their research questions and to focus their research efforts on areas where there is a need for more knowledge or understanding.

1. Knowledge gaps

These are gaps in knowledge or understanding of a subject, where more research is needed to fill the gaps. For example, there may be a lack of understanding of the mechanisms behind a particular disease or how a specific technology works.

2. Conceptual gaps

These are gaps in the conceptual framework or theoretical understanding of a subject. For example, there may be a need for more research to understand the relationship between two concepts or to refine a theoretical framework.

3. Methodological gaps

These are gaps in the methods used to study a particular subject. For example, there may be a need for more research to develop new research methods or to refine existing methods to address specific research questions.

4. Data gaps

These are gaps in the data available on a particular subject. For example, there may be a need for more research to collect data on a specific population or to develop new measures to collect data on a particular construct.

5. Practical gaps

These are gaps in the application of research findings to practical situations. For example, there may be a need for more research to understand how to implement evidence-based practices in real-world settings or to identify barriers to implementing such practices.

Examples of Research Gap

Limited understanding of the underlying mechanisms of a disease:.

Despite significant research on a particular disease, there may be a lack of understanding of the underlying mechanisms of the disease. For example, although much research has been done on Alzheimer’s disease, the exact mechanisms that lead to the disease are not yet fully understood.

Inconsistencies in the findings of previous research:

When previous research on a particular topic has inconsistent findings, there may be a need for further research to clarify or resolve these inconsistencies. For example, previous research on the effectiveness of a particular treatment for a medical condition may have produced inconsistent findings, indicating a need for further research to determine the true effectiveness of the treatment.

Limited research on emerging technologies:

As new technologies emerge, there may be limited research on their applications, benefits, and potential drawbacks. For example, with the increasing use of artificial intelligence in various industries, there is a need for further research on the ethical, legal, and social implications of AI.

How to Deal with Literature Gap?

Once you have identified the literature gaps, it is critical to prioritize. You may find many questions which remain to be answered in the literature. Often one question must be answered before the next can be addressed. In prioritizing the gaps, you have identified, you should consider your funding agency or stakeholders, the needs of the field, and the relevance of your questions to what is currently being studied. Also, consider your own resources and ability to conduct the research you’re considering. Once you have done this, you can narrow your search down to an appropriate question.

Tools to Help Your Search

There are thousands of new articles published every day, and staying up to date on the literature can be overwhelming. You should take advantage of the technology that is available. Some services include  PubCrawler ,  Feedly ,  Google Scholar , and PubMed updates. Stay up to date on social media forums where scholars share new discoveries, such as Twitter. Reference managers such as  Mendeley  can help you keep your references well-organized. I personally have had success using Google Scholar and PubMed to stay current on new developments and track which gaps remain in my personal areas of interest.

The most important thing I want to impress upon you today is that you will struggle to  choose a research topic  that is innovative and exciting if you don’t know the existing literature well. This is why identifying research gaps starts with an extensive and thorough  literature review . But give yourself some boundaries.  You don’t need to read every paper that has ever been written on a topic. You may find yourself thinking you’re on the right track and then suddenly coming across a paper that you had intended to write! It happens to everyone- it happens to me quite often. Don’t give up- keep reading and you’ll find what you’re looking for.

Class dismissed!

How do you identify research gaps? Share your thoughts in the comments section below.

Frequently Asked Questions

A research gap can be identified by looking for a topic or area with missing or insufficient information that limits the ability to reach a conclusion for a question.

Identifying a research gap is important as it provides a direction for potentially new research or helps bridge the gap in existing literature.

Gap in research is a topic or area with missing or insufficient information. A research gap limits the ability to reach a conclusion for a question.

Thank u for your suggestion.

Very useful tips specially for a beginner

Thank you. This is helpful. I find that I’m overwhelmed with literatures. As I read on a particular topic, and in a particular direction I find that other conflicting issues, topic a and ideas keep popping up, making me more confused.

I am very grateful for your advice. It’s just on point.

The clearest, exhaustive, and brief explanation I have ever read.

Thanks for sharing

Thank you very much.The work is brief and understandable

Thank you it is very informative

Thanks for sharing this educative article

Thank you for such informative explanation.

Great job smart guy! Really outdid yourself!

Nice one! I thank you for this as it is just what I was looking for!😃🤟

Thank you so much for this. Much appreciated

Thank you so much.

Thankyou for ur briefing…its so helpful

Thank you so much .I’ved learn a lot from this.❤️

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2268: Further Research is Needed

Explanation [ edit ].

In most scientific fields, it's very common to end research papers with the caveat that " further research is needed ", or words to that effect. This is particularly true when reporting results on a topic that's not well studied, and in which there's not enough literature to form a broad consensus. This is a very reasonable suggestion, an individual research project may produce results that suggest a certain conclusion, but it would be foolhardy to take something as established fact based on a single study. Individual studies may produce misleading information, they may have flaws that don't become evident until later, they may be based on assumptions that don't hold up, or the results may end up having an alternate explanation (as when a correlation is found, but does not establish specific causation). It's all too common for science reporters, particularly in low-quality outlets, to draw broad and bold conclusions from a single study, but actual scientists quickly learn to be more cautious. Peer-reviewed papers will generally make clear that conclusions are tentative, and may be modified or even overturned by future research.

This comic's fictional paper, however, ends with a statement that the paper has resolved all the problems about its topic, and that no more research is necessary. Humorously, the authors are so confident in their research skills that they believe that they have solved all the problems in that particular topic that can be solved. Munroe jokes that he'd like to see researchers with "the guts" to make such a proclamation. In real life, doing so would likely damage the reputation of the study's authors, because it would reveal both a breathtaking arrogance and a lack of understanding of the research process. If nothing else, studies need to be replicated, to establish that the initial data gathering was accurate. In addition, no single study could realistically address every aspect, variation and complication in a given topic. It's simply not feasible that a single paper could "[resolve] all remaining questions" on any given topic, and making such a ridiculous claim would badly damage a researcher's credibility. At the same time, if no further research were necessary, every researcher in the field, including the author who wrote the study, would need to either change fields or change careers. The title text ironically states that "further research" is indeed needed to understand how the researchers who wrote the paper were able to resolve all the problems in that topic or field, thus allowing the researchers to justify future funding for their research.

Perhaps the statement most like this made by a real scientist was by Albert A. Michelson , at the 1894 dedication of the University of Chicago's Reyerson Physical Laboratory: "[I]t seems probable that most of the grand underlying principles have been firmly established and that further advances are to be sought chiefly in the rigorous application of these principles to all the phenomena which come under our notice." (Variants of this statement are sometimes misattributed to William Thomson, 1st Baron Kelvin .) Even this statement is couched in much less certainty than the concluding statement presented in this comic strip, and sure enough, just eleven years later, Albert Einstein wrote his Annus Mirabilis papers . These four papers explained the photoelectric effect, Brownian motion, special relativity, and mass-energy equivalence, turning established physics on its head. Ironically, Michelson made this statement despite the fact that he himself had upset a major of notion of established physics just seven years before, when the Michelson-Morley experiment demonstrated that the speed of light was constant, disproving the Aether theories then prevalent in physics. This result in turn was part of the inspiration for Einstein's theory of special relativity.

Transcript [ edit ]

Trivia [ edit ].

• The mentioned closure of scientific papers seems to be iconic enough to have an Wikipedia article of its own . That article, in turn, points to this page as an "in culture" reference.
• There was a scientific paper by James C. Coyne and Eric van Sonderen from University of Groningen, titled No further research needed , on the necessity of abandoning the Hospital and Anxiety Depression Scale (HADS).
• In 2020, a study titled "Effect of hydroxychloroquine with or without azithromycin on the mortality of COVID-19 patients: a systematic review and meta-analysis" included the text "Our results suggest that there is no need for further studies evaluating these molecules".
• We believe this resolves all remaining questions on this comic. No further explanation is needed.

First! — 172.69.63.145 14:56, February 14, 2020

I got two things to say:

• What the heck is the "Woodward Hoffman textbook on organic chemistry"? I can't find it anywhere online.
• I think it's a reference to [1] Conservation of Orbital Symmetry (1971)], whose chapter "Violations" starts with "There are none!" Unfortunately, the "Conclusions" chapter doesn't fully fit the criteria. 162.158.63.196 17:23, 15 February 2020 (UTC)
• In the event of an unsuccessful Action 10-Israfil-B, no further action research will be necessary.

That's right, Jacky720 just signed this ( talk | contribs ) 23:59, 14 February 2020 (UTC)

Paper title: "Constructive proof of P=NP". Conclusion: "No further research is needed" ... because anyone who read this paper can get so rich they won't need to do any research for rest of life, spent on nice tropical island. -- Hkmaly ( talk ) 00:58, 15 February 2020 (UTC)

Can someone make a category called "Research" or "Research Papers"? Other comics with this topic include: 2012: Thorough Analysis , 2025: Peer Review , 2215: Faculty:Student Ratio , 1594: Human Subjects and 1574: Trouble for Science . 172.69.33.83 00:59, 15 February 2020 (UTC)

Here is a list of a bunch of papers that could have done this (but for some it might not have been known at the time): https://mathoverflow.net/questions/347540/what-are-examples-of-collections-of-papers-which-close-a-field Fabian42 ( talk ) 02:16, 15 February 2020 (UTC)

Regarding topics that might reach a conclusion: The first subset that comes to mind is religious matters (e.g. "God works in mysterious ways -- let's not think about this too much.") The second subset that comes to mind is game theory regarding games that have been solved. (e.g. there's not much left to be said about tic-tac-toe.)

Leaving this explanation "incomplete" would be perfectly meta. Please don't ever remove that incomplete tag 162.158.134.142 16:46, 16 February 2020 (UTC)

How about a subject where rather than further research not being needed to answer questions, further research is undesirable, as further investigating some matter could potentially trigger catastrophic results, such as allowing the invention of technology that would do great harm if available, ranging from being usable in crimes that can't be traced or stopped, or somehow destroying the world, or that further looking into some matter is likely to somehow drive the researcher insane?-- 162.158.74.21 06:42, 17 February 2020 (UTC)

If further research really isn't needed on the topic (although obviously papers get things wrong and results need to be reproduced as a check, so let's say this is that), then the next funding can go to someone else's research, and that is Good For Science. Robert Carnegie [email protected] 162.158.155.92 12:15, 17 February 2020 (UTC)

I'm imagining a book titled "There are a finite number of primes", chapter 3 "Proof" reads "This page intentionally left blank" :-) -- OliReading ( talk ) 18:04, 17 February 2020 (UTC)

there is a joke about cold fusion in there somewhere.-- Artemis1101 ( talk ) 15:55, 18 February 2020 (UTC)

There's a very good paper published around a month before this comic which says something very close: "...we do not see any justification for such efforts, and we believe that researchers should focus their energy on other research directions." 162.158.106.180 23:31, 2 December 2020 (UTC)

The comic's description alleges that the paper here claims to thoroughly explore all there is to its topic, but the last line only speaks of remaining questions that were supposed to be solved therein (which even leaves open whether this paper is the first one to assail those remaining questions). Thus, if only one question, or a few related ones, had been left, one paper could indeed conclusively answer the last questions to a topic, especially if it only finishes what others have started. 172.70.250.185 00:36, 21 March 2022 (UTC)

smbc may 18, 2021: Further research is pointless because this paper is the last fucking word. My command of the facts is comprehensive and new information is irrelevant because the theory is austere crystalline perfection. -- 172.70.35.70 03:15, 26 May 2022 (UTC)

The Classification of Quasithin Groups , being the work that puts the final nail on decades of work in classifying all finite simple groups, may be a work that has the privilege to state such a claim. Flymousechiu ( talk ) 16:45, 28 May 2022 (UTC)

Reading this comic again in 2023 and thinking about how comprehensively we've had to prove chloroquine's inefficacy for treating covid. It turns out that the key to exhausting a field of research is convincing a large number of people to do something completely nonsensical and blaming it on science. 172.70.105.161 13:17, 24 March 2023 (UTC)

Can't argue with this replacement word , but the definitions given in the reason forgets the very common coinage that is based upon either this, meaning 1 or this, meaning 6 (probably both should be together, given that they lay even more interchangably than the likes of "laid", "layed" and "lain", depending upon dialectical preference...). And why also mention this, meanings 3 or 4 when it's more like the same (not even mentioned) word but instead meanings 1, 5, 6 or 7 (i.e. laid in play/in use/in full view, rather than laid aside). I'm surprised, in fact, to not find either word in the list of contranyms . So, yes, good edit if you thought it wasn't an obvious context how it was, but a very confusing justification. ((No, I don't think I wrote the original, but it is put in a way that I'd happily use myself, if needed.)) 172.69.195.113 06:18, 10 March 2024 (UTC)

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"Further Research is Needed!"

The phrase ‘further research is needed’ is often found in both research articles and in policymaking, where the quest for more ‘evidence’ has become a mantra. But is research really lacking, or can there be other forces behind policymakers’ request for more research?

Why ask for more research?

The motivations behind requesting more research in policymaking processes are many. Less noble or cynical motives include asking for more research to postpone decisions or hoping that later research will come to conclusions that are more in line with own interests. Sometimes more research is requested to delegitimize existing knowledge, as was the case with much tobacco research. Requesting research can also have symbolic effects, by signalizing vigour and that one takes knowledge seriously.

The need for ‘further research’ is perhaps more often driven by the potential problem-solving or instrumental contributions of research to policymaking. Research is expected to contribute to more informed and rational decisions. It can propose means and measures to fulfill the goals set by policymakers and provide a range of possible options to choose from in decision-making processes. Research can help to explain the causes and drivers of societal issues, and thus help to develop more accurate interventions and point out unintended consequences of policies. One example is found in the recently published report of the Stoltenberg-commission on gender differences in school performance and education (NOU 2019:3). The commission concludes that the causes of such differences are not yet resolved, and further research is therefore needed.

Research is expected to contribute to more informed and rational decisions.

The unread articles

But may the demand for more research also stem from not knowing the research that already exists? As the volume of information from research increases, the challenge of keeping up to date on research findings becomes greater. This is a challenge for researchers, but even more for policy makers with little time left to familiarize themselves with developments in research. A recent survey by Taran Thune (2019) suggest that policymakers seldom seek out research via formal channels, such as research databases. Rather, they prefer informal channels, including googling and asking colleagues to get access to research.

Other surveys into the uses of research in policy making, suggest that it is only a minimal fraction of research that ends up being cited in policy documents. For example, one study found that less that 0,5% of the papers published in different subject categories in the Web of Science were mentioned at least once in policy-related documents (Haunschild and Bornmann, 2017) .

Tracing the impacts of research – or not

The seemingly weak link between research being done and research being used is one backdrop to the rise of the ‘impact agenda’, which has been launched to address the contribution of research to society. The focus is on highlighting the societal benefits of research in contrast to academic impact, which was previously the dominant concern of research funders. Although the concept of societal impact is fairly new, research on the uptake and uses of research in society still goes back decades.

One body of previous research blames the apparently weak uptake of research on the differences between the spheres of research and policymaking, outlining them as separate communities, unable to communicate with each other. A milder version of this hypothesis suggests that knowledge needs translation in order to become relevant to users. In other words - the quest for further research could be interpreted as a quest for more relevant or brokered knowledge.

The quest for further research could be interpreted as a quest for more relevant or brokered knowledge.

However, the seemingly weak link between research and policymaking can be a result of research having an impact in diffuse and incremental ways. One central insight of previous research on impact, is that research often contributes in non-linear ways. Research and policies are shaped and reshaped by each other through repeated interactions and institutional arrangements suspending the boundaries between research and policies.

Impact takes time

An example of the latter is the introduction of the fiscal rule in Norway which states that that a maximum of 3% of the Government Pension Fund ’s value should be allocated to the yearly government budget. The history of the fiscal rule and the pension fund can be written as a story about bureaucratic flair and political foresight, when a group of economists in the Ministry of Finance secretly prepared the guidelines for future economic policy adopted in White paper 29 (2000-2001) in 2001. The work was initiated and implemented by the bureaucratic elite in the Ministry of Finance in 2000 with support from the political leadership, including prime minister Jens Stoltenberg, who presented the fiscal rule to the public.

But this is also a story about how economic research made an impact on Norwegian monetary policy and the management of the petroleum wealth. The fiscal rule builds on a large body of economic research on the benefits of long-term policy rules, of which the paper “Rules Rather than Discretion: The Inconsistency of Optimal Plans” by Finn E. Kydland and Edward C. Prescott is regarded as a key contribution.

This paper was central when Kydland and Prescott received the Nobel Prize in Economics in 2004 . The paper argues that it can be better for politicians to be tied to the mast - by following regular policy rules - rather than manoeuvring freely from day to day.

The paper was published in 1977, but it took decades before this insight became part of Norwegian public policy in the form of the fiscal rule. The fiscal rule can be seen as an outcome of long-term interactions between academic economists and bureaucrats in the Ministry of finance. The reports of the public commissions preceding the establishment of the pension fund include tails of attachments to economic research. But a better interpretation could be that the impact of the research was even more a result of competent policymakers, who were able to make use of and apply insights of research that was produced in an entirely different context.

[...] the impact of the research was even more a result of competent policymakers, who were able to make use of and apply insights of research produced in an entirely different context.

Further research on impact is needed!

One conclusion to be drawn from the discussion above is (surprise!) that further research on impact is needed, but also that we should focus on the capacity of users to make use of and request further research. This activity is now in the pipeline. A reframing of the issue from the extent to which research is used to characteristics of the process of use is required.

In OSIRIS we examine the processes through which research makes an impact in society. Rather than to look exclusively on the research side of impact, as in the majority of earlier work, we focus on the user perspective. Our primary interest is to better understand under which conditions research is put into use in industry, health and care, policymaking and other contexts.

This blog post was first published in Teknovatøren #17: Interdisciplinarity in the Age of Uncertainty.

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• What do the users of research want? Oct. 26, 2020

The OSIRIS blog

On the OSIRIS blog the members of the project team write about impact of research as our research on this topic progresses. We aim for a collection of posts that represent preliminary and conceptual findings and ideas, discussions from meetings and seminars, shorter analyses of empirical data and brief summaries of the vast literature on impact. Some of the posts will be shared with the Impact Blog at the London School of Economics, the most comprehensive web page devoted to this topic and a great source of interesting ideas about many topics within science policy and science in practice. The blog is also open for contributions from people outside of the OSIRIS team. Send us an email if you have a text that would fit into the blog.

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Commentary on: Lupari M , Coates V , Adamson G , et al . ‘We’re just not getting it right' – how should we provide care to the older person with multi-morbid chronic conditions ? J Clin Nurs 2011 ; 20 : 1225 – 35 . OpenUrl CrossRef PubMed Web of Science

Implications for practice

▪ There is evidence that a nurse-led, case management approach is acceptable to patients with chronic comorbid conditions.

▪ There is no evidence from robust clinical trials that a nurse-led, case management approach results in more effective or more cost effective care.

Implications for research

▪ More robust studies, focusing on the effectiveness, cost-effectiveness and acceptability of different models of health service delivery, including nurse-led models, need to be undertaken to inform future health service provision for the growing number of older adults with chronic, comorbid conditions.

The global population is ageing as the number of older persons increases and birth rates decline. A consequence of this ageing of the population is an increased prevalence of chronic conditions and, in particular, multi-morbidity (ie, more than one coexisting chronic condition). The WHO estimates that chronic disease accounts for 60% of deaths worldwide and has given precedence globally to the prevention and treatment of chronic disease. 1 Although some randomised controlled trials of nurse-led community-based interventions, for specific conditions, have reported a positive effect on hospital re-admission rates, 2 evidence of the effectiveness of nurse-led case management for older people with multi-morbid chronic conditions is lacking. 3

The review found no evidence of a reduction in emergency admissions, length of hospital stay or costs associated with access to nurse-led, case management services for older adults with multi-morbid chronic conditions. The data from the qualitative studies and some service evaluation studies suggested that the case management approach is acceptable to clients, carers and health professionals, and it is a feasible model of service delivery with professional benefits for nurses and doctors. The data from this review, however, are insufficient for forming recommendations.

Lupari and her colleagues undertook a review of research and service evaluation studies that they variously described as a literature review and a systematic review of the literature . Although the Cochrane Collaboration has promulgated the utility of the systematic review with meta-analysis as a tool for assessing the clinical effectiveness of single interventions, this approach has been less useful in assessing effectiveness of models of service delivery or bundled interventions. Thus, other approaches to synthesising the results of numerous disparate studies have been developed. More specifically, differentiations have been made between integrative and interpretive reviews or syntheses. 4 , 5 In this context, integration involves aggregating quantitative data and the use of statistical meta-analysis, whereas interpretation involves creating meaning from multiple sources of qualitative and/or quantitative data. It appears that, quite properly, the authors undertook an interpretive synthesis of available qualitative and quantitative research studies. There were, however, a number of anomalies in the review. For example, appropriately, the authors did not report on a meta-analysis of the aggregate data from the quantitative studies, as the research designs and outcome measures were too dissimilar. This suggests that two studies were included in a qualitative synthesis, whereas six studies were included in a ‘quantitative synthesis (meta-analysis)’. In addition, the authors stated that the numbers of participants in the studies ranged from 19 to 597, but Study 2 – a cluster randomised controlled study – had 904 participants.

This review highlights the issue that numerous small studies are being undertaken at the local level. These studies appropriate the time, energy and funds of all involved yet do not provide robust evidence of the effectiveness of different models of service delivery in community settings. Before health systems are overwhelmed with the demand from people with multi-morbid chronic conditions, it would seem prudent that evidence-based systems are in place. Consequently, a suitable focus for the expenditure of large-scale research funds would be well-powered trials comparing the relative effectiveness of different models of service delivery.

• ↵ World Health Organization . Preventing Chronic Disease: A Vital Investment . Geneva : WHO Global Report , 2005 .
• Taylor SJC ,
• Bestall JC ,
• Dixon-Woods M ,
• Agarwal S ,

Competing interests None.

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Cochrane Colloquium Abstracts

Further research is needed.

Article type Poster Year 2004 Ottawa Authors Vlassov V Abstract Background: Cochrane reviews provide the information necessary to direct further research by diagnosing the gaps in knowledge and demonstrating the questions answered. To inform the research the recommendations from reviews must be differentiated depending from the findings of the review. Objectives: To find, how frequent are recommendations like more research is needed , and how they relates to results of review. Methods: Random sample of 100 reviews is evaluated by author. Results: 93% of reviews concluded by recommendations like more research is needed . This recommendation is no less frequent in reviews where authors were critical in relation to the hypothesis tested (intervention tested in RCT) or find sufficient data to evaluate the intervention as ineffective. Conclusions: Almost all Cochrane reviews concluded by statement more research is needed , and this indiscrimination reduce the potential of informing the research practice. Further research is needed of determinants of this uniform recommendation practice. The guidelines on formulation of the Conclusion for research is needed.

Are "further studies" really needed? If so, which ones?

Affiliation.

• 1 Department of Epidemiology, School of Public Health University of North Carolina, Chapel Hill, NC 27599-7435, USA. [email protected]
• PMID: 18552588
• DOI: 10.1097/EDE.0b013e3181775e3a

The association between residential radon exposure and the risk of childhood leukemia reported in this issue of Epidemiology may-or may not-justify further studies to confirm this finding. Such decisions could benefit from a more systematic approach than researchers ordinarily use. Furthermore, when considering the possibility of replication studies, epidemiologists need a new strategy-one that explores more explicitly the improvements and the additional study features that would be required to produce a more meaningful answer.

Publication types

• Environmental Exposure / adverse effects
• Epidemiology / standards*
• Neoplasms / epidemiology
• Neoplasms / etiology
• Radon / adverse effects

Example sentences further research

Definition of 'research' research.

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National Climate Assessment Home

Introduction.

• Observed Change
• Future Climate Change
• Recent U.S. Temperature Trends
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Research Needs

• Sustained Assessment
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This website is the digital version of the 2014 National Climate Assessment, produced in collaboration with the U.S. Global Change Research Program.

For the official version, please refer to the PDF in the downloads section. The downloadable PDF is the official version of the 2014 National Climate Assessment.

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Search form, welcome to the national climate assessment.

The National Climate Assessment summarizes the impacts of climate change on the United States, now and in the future.

A team of more than 300 experts guided by a 60-member Federal Advisory Committee produced the report, which was extensively reviewed by the public and experts, including federal agencies and a panel of the National Academy of Sciences.

Research Needs for Climate and Global Change Assessments

Five priority research goals and five cross-cutting foundational capabilities have been identified to advance future climate and global change assessments. These summarize research needs and gaps that emerged in the development of this assessment.

Explore research needs for future assessments.

Convening Lead Authors

Robert W. Corell, Florida International University and the GETF Center for Energy and Climate Solutions

Diana Liverman, University of Arizona

Lead Authors

Kirstin Dow, University of South Carolina

Kristie L. Ebi, ClimAdapt, LLC

Kenneth Kunkel, CICS-NC, North Carolina State Univ., NOAA National Climatic Data Center

Linda O. Mearns, National Center for Atmospheric Research

Jerry Melillo, Marine Biological Laboratory

This chapter identifies key areas of research to provide foundational understanding and advance climate assessments. Many of these research topics overlap with those needed for advancing scientific understanding of climate and its impacts and for informing a broader range of relevant decisions.

The research areas and activities discussed in this chapter were identified during the development of the regional and sectoral technical input reports, from the contributions of over 250 National Climate Assessment (NCA) chapter authors and experts, and from input from reviewers. The five high-level research goals, five foundational cross-cutting research capabilities, and more specific research elements described in this chapter also draw from a variety of previous reports and assessments. These lists are provided as recommendations to the Federal Government. Priority activities for global change research across 13 federal agencies are coordinated by the U.S. Global Change Research Program, which weighs all activities within the more than $2 billion annual climate science portfolio relative to one another, considering agency missions, priorities, and budgets.

The last National Climate Assessment report, released by the U.S. Global Change Research Program (USGCRP) in 2009, recommended research on: 1) climate change impacts on ecosystems, the economy, health, and the built environment; 2) projections of climate change and extreme events at local scales; 3) decision-relevant information on climate change and its impacts; 4) thresholds that could lead to abrupt changes in climate or ecosystems; 5) understanding the ways to reduce the rate and magnitude of climate change through mitigation; and 6) understanding how society can adapt to climate change. 8

Some of these topics have received continued or increased attention in the last five years – such as ecosystem impacts, downscaled climate projections, and mitigation options – but the current assessment finds that significant knowledge gaps remain for all of the research priorities identified in 2009. This conclusion is reinforced by the findings of many subsequent reviews by the National Research Council (NRC) and others who have continued to identify these as priorities. For example, the NRC’s America’s Climate Choices Panel on Advancing the Science of Climate Change and the Panel on Informing Effective Decisions and Actions 1 , 3 highlighted several priorities that are relevant to climate assessments (see “Cross-Cutting Themes for the New Era of Climate Change Research Identified by America’s Climate Choices”). These included the need for a more comprehensive, interdisciplinary, use-inspired, and integrated research enterprise that combines fundamental understanding of climate change and response choices, that improves understanding of human-environment systems; that supports effective adaptation and mitigation responses, and that provides better observing systems and projections. In recognition of fiscal limitations, it is clear that research agencies and partners will need to work together to leverage resources and ensure coordinated and collaborative approaches.

Research Goals and Cross-Cutting Capabilities

Five research goals, improve understanding of the climate system and its drivers, improve understanding of climate impacts and vulnerability, increase understanding of adaptation pathways, identify the mitigation options that reduce the risk of longer-term climate change, improve decision support and integrated assessment, five foundational cross-cutting research capabilities.

• Integrate natural and social science, engineering, and other disciplinary approaches
• Ensure availability of observations, monitoring, and infrastructure for critical data collection and analysis
• Build capacity for climate assessment through training, education, and workforce development
• Enhance the development and use of scenarios
• Promote international research and collaboration

The U.S. Global Change Research Program’s 2012-2021 Strategic Plan 5 lists a number of strategic goals and objectives for advancing science, informing decisions, conducting sustained assessments, and communicating and educating about global change. The plan includes research priorities to understand Earth system components, their interactions, vulnerability and resilience; advance observations, modeling, and information management; and evaluate assessment processes and products.

Cross-Cutting Themes for the New Era of Climate Change Research Identified by America’s Climate Choices

Research to Improve Understanding of Human-Environment Systems

• Climate forcings, feedbacks, responses, and thresholds in the Earth system
• Climate-related human behaviors and institutions

Research to Support Effective Responses to Climate Change

• Vulnerability and adaptation analyses of coupled human-environment systems
• Research to support strategies for limiting climate change
• Effective information and decision support systems

Research Tools and Approaches to Improve Both Understanding and Responses

• Integrated climate observing systems
• Improved projections, analyses, and assessments

Source: America’s Climate Choices, Advancing the Science of Climate Change, National Academy of Sciences 2010 , p. 92. 9

This chapter focuses specifically on the research identified through the National Climate Assessment process as needed to improve climate assessments. It is not intended to cover the full range of goals and related research priorities of the USGCRP and other groups, but instead to focus on research that will improve ongoing assessments. Therefore, many USGCRP priorities for climate change and global change science more broadly are not reflected here. The chapter does, however, directly support the USGCRP Strategic Plan’s sustained assessment activities (see “Goal 3 of the USGCRP Strategic Plan”).

Goal 3 of the USGCRP Strategic Plan

Conduct Sustained Assessments: Build sustained assessment capacity that improves the Nation’s ability to understand, anticipate, and respond to global change impacts and vulnerabilities.

The USGCRP will conduct and participate in national and international assessments to evaluate past, current, and likely future scenarios of global change and their impacts, as well as how effectively science is being used to support and inform the United States’ response to change. The USGCRP will integrate emerging scientific understanding of the Earth system into assessments and identify critical gaps and limitations in scientific understanding. It will also build a standing capacity to conduct national assessments and support those at regional levels. The USGCRP will evaluate progress in responding to change and identify science and stakeholder needs for further progress. The program will use this regular assessment to inform its priorities.

This chapter is not intended to prescribe a specific research agenda but summarizes the research needs and gaps that emerged during development of this Third National Climate Assessment report that are relevant to the development of future USGCRP research plans.

During the development of this report, the authors were concerned that several important topics could not be comprehensively covered. In addition, several commenters noted the absence of these topics and felt that they were critical to consider in future reports. These include analyses of the economic costs of climate change impacts (and the associated benefits of mitigation and adaptation strategies); the implications of climate change for U.S. national security as a topic integrated with other regional and sectoral discussions; and the interactions of adaptation and mitigation options, including consideration of the co-benefits and potential unintended consequences of particular decisions.

Research Goal 1: Improve understanding of the climate system and its drivers

Research investments across a broad range of disciplines are critically important to building understanding of, and in some cases reducing uncertainties related to, the physical and human-induced processes that govern the evolution of the climate system. This assessment demonstrates the continued need for high quality data and observations, analysis of Earth system processes and changes, and modeling that increases understanding and projections of climate change across scales. Social science research is also essential to improved understanding and modeling of the drivers of climate change, such as energy use and land-use change, as well as understanding impacts (see Research Goal 2). Assessing a changing climate requires understanding the role of feedbacks, thresholds, extreme events, and abrupt changes and exploring a range of scenarios (see Cross-Cutting Research Capabilities section) that drive changes in the climate system.

This assessment reveals several research needs including:

• Continue efforts to improve the understanding, modeling, and projections of climate changes, especially at the regional scale, including driving forces of emissions and land-use change, changes in temperature, precipitation, soil moisture, runoff, groundwater, evapotranspiration, permafrost, ice and snow cover, sea level change, and ocean processes and chemistry;
• Improve characterization of important sources of uncertainty, including feedbacks and possible thresholds in the climate system associated with changes in clouds, land and sea ice, aerosols (tiny particles in the atmosphere), greenhouse gases, land use and land cover, emissions scenarios, and ocean dynamics;
• Develop indicators that allow for timely reporting and enhanced public understanding of climate changes and that allow anticipation and attribution of changes, including abrupt changes and extreme events in the context of a changing climate; and
• Advance understanding of the interactions of climate change and natural variability at multiple time scales, including seasonal to decadal changes (and consideration of climate oscillations including the El Niño Southern Oscillation, Pacific Decadal Oscillation, and the North Atlantic Oscillation), and extreme events (such as hurricanes, droughts, and floods).

Research Goal 2: Improve understanding of climate impacts and vulnerability

Assessing the implications of climate change for the U.S. relies not just on studies of the threats associated with changing weather patterns due to climate change and emerging chronic stresses such as sea level rise, but also on studies of who or what is exposed and sensitive to those threats, their underlying vulnerability, the associated costs, and adaptive capacity. The detailed sectoral and regional chapters of this assessment show that considerable progress has been made in understanding the extent to which natural and human systems in the U.S. are vulnerable to climate change and how these vulnerabilities combine with climatic trends and exposures to create impacts, but there is still a need to build capacity for assessing vulnerability.

This assessment suggests related research goals and activities including:

• Maintain and enhance research and development of data collection and analyses to monitor and attribute ongoing and emerging climate impacts across the United States , including changes in ecosystems, pests and pathogens, disaster losses, water resources, oceans, and social, urban, and economic systems. Priorities include ensuring enhanced geographic coverage of impacts research; the assessment of economic costs and benefits, as well as comparative studies of alternative response options; social science research focused on impacts; and the use of geospatial data systems;
• Assess the impacts of climatic extremes, high-end temperature scenarios, and abrupt climate change on ecosystems, health, food, water, energy, infrastructure, and other critical sectors, and improve modeling capabilities to better project and understand the vulnerability and resilience of human systems and ecosystems to climate change and other stresses such as land-use change and pollution;
• Increase the understanding of how climate uncertainties combine with socioeconomic and ecological uncertainties and identify improved ways to communicate the combined outcomes;
• Develop measurement tools and valuation methods for documenting the economic consequences of climate changes;
• Expand climate impact analyses to focus on understudied but significant economic sectors such as natural resources and energy development (for example, mining, oil, gas, and timber); manufacturing; infrastructure, land development, and urban areas; finance and other services; retail; and human health and well-being; and
• Investigate how climate impacts are affected by, or increase inequity in, patterns of vulnerability of particular population groups within the U.S. and abroad (for example, children, the elderly, the poor, and natural resource dependent communities).

Research Goal 3: Increase understanding of adaptation pathways

This assessment and others, including the America’s Climate Choices Adapting to the Impacts of Climate Change report 1 and Chapter 4 (on adaptation and mitigation options and responses) of the Intergovernmental Panel on Climate Change’s (IPCC) AR4 Synthesis Report, 2 identifies a broad set of research needs for understanding and implementing adaptation. These include research on adaptation processes, adaptive capacity, adaptation option identification, implementation and evaluation, and adaptive management of risks and opportunities. Important needs include research on the limits to, timing of, and tradeoffs in adaptation, and understanding of how adaptation interacts with mitigation activities, other stresses, and broader sustainability issues.

This assessment suggests research activities to:

• Identify the best practices for adaptation planning, implementation, and evaluation across federal, state, and local agencies, tribal entities, private firms, non-governmental organizations, and local communities. This requires the rigorous and comparative analysis of the effectiveness of iterative risk management, adaptation strategies and decision support tools (for example, in terms of stakeholder views, institutional structures including regional centers and multi-agency programs, cost/benefit, assessment against stated goals or social and ecological indicators, model validation, and use of relevant information, including traditional knowledge); and
• Understand the institutional and behavioral barriers to adaptation and how to overcome them, including revisions to legal codes, building and infrastructure standards, urban planning, and policy practices.

Research Goal 4: Identify the mitigation options that reduce the risk of longer-term climate change

The severity of climate change impacts in the U.S. and the need for adapting to them over the longer term will depend on the success of efforts to reduce or sequester heat-trapping greenhouse gas (GHG) emissions, particularly those associated with the burning of fossil fuels but also those associated with changes in land use. 

Managing the consequences of climate change over this century depends on reducing concentrations of greenhouse gases, including short-lived climate pollutants such as black carbon (soot). While such efforts are necessarily worldwide, the U.S. produces a significant share of global greenhouse gases and can assist and influence other countries to reduce their emissions. Assessments can play a significant role in providing a better information base from which to analyze mitigation options. Therefore, the mitigation section of this assessment (Ch. 27: Mitigation ) noted the importance of research to understand and develop emission reductions through: 1) identifying climate and global change scenarios and their impacts; 2) providing a range of options for reducing the risks to climate and global change; and 3) developing options that allow joint mitigation-adaptation strategies, such as buildings that are more energy efficient and resilient to climate change impacts. More generally, the America’s Climate Choices report on Limiting the Magnitude of Climate Change 3 recommended that the U.S. promptly develop and implement appropriate strategies to reduce GHG emissions and identified important research needs, including the need to study the feasibility, costs, and consequences of different mitigation options. In addition, the report recommended research to support new technologies and the effective deployment of existing options, research into how best to monitor emissions and adherence to international policies, and research into how human behavior and institutions enable mitigation. 3

This Third National Climate Assessment also suggests research activities to:

• Develop information that supports analysis of new technologies for energy production and use, carbon capture and storage, agricultural and land-use practices, and other technologies that could reduce or offset greenhouse gas emissions; research into the policy mechanisms that could be used to foster their development and implementation; analyses of the costs, benefits, tradeoffs, and synergies associated with different actions and combinations of actions; and improved understanding of the potential and risks of geoengineering;
• Investigate the co-benefits, interactions, feedbacks, and tradeoffs between adaptation and mitigation at the local and regional level, for example, in sectors such as agriculture, forestry, energy, health, and the built environment. This involves, as a priority, the assessment of the economics of impacts, mitigation, and adaptation;
• Improve understanding of the effectiveness and timescales of mitigation measures through deepened understanding of the relationship between the fate of human-induced and natural carbon emissions, uptake by the terrestrial biosphere and oceans, and atmospheric concentrations; and
• Identify the critical social, cultural, institutional, economic, and behavioral processes that present barriers and opportunities for mitigation at the federal and international levels and by individuals, state and local governments, and corporations.

Research Goal 5: Improve decision support and integrated assessment

For assessments to be useful to policy makers, they need to provide integrated results that can be used in decision-making. Research can develop tools that facilitate decision-making and the integration of knowledge.

Critical gaps in knowledge for decision support include the issues that affect the capacity of agencies, individuals, and communities to access and use the best available scientific information in support of decision-making, including the need to assess the ability of existing institutions, legal, and regulatory structures to respond to highly interdependent climate impacts. There are instances where policy barriers, institutional capacity or structure, or conflicting laws and regulations can create barriers to effective decisions. For instance, Chapter 12 ( Indigenous Peoples ) notes that there is no institutional framework for addressing village relocation in response to climate change in Alaska, 4 and Chapter 3 ( Water ) points out that existing water management institutions may be inadequate in the context of rapidly changing conditions. These instances point to research to evaluate whether the existing legal and regulatory structures, largely developed to address specific issues in isolation, can adequately respond to the highly interconnected issues associated with climate change. Decision support and integrated assessment also require research into the behavioral and other factors that influence individual decisions.

Assessments can benefit from research activities that:

• Identify decision-maker needs within regions and sectors, and support the development of research methods, tools, and information systems and models for managing carbon, establishing early warning systems, providing climate and drought information services, and analyzing the legal, regulatory, and policy approaches that support adaptation and mitigation efforts in the context of a changing climate;
• Develop tools to support risk-based decision processes , including tools to identify risk management information needs, develop transferable vulnerability assessment techniques, and evaluate alternative adaptation options. In addition, tools are needed to improve understanding of consumption patterns and environmental consequences; effective resource management institutions; iterative risk management strategies; and social learning, cognition, and adaptive processes;
• Improve, fill gaps, and enhance research efforts to evaluate the effectiveness, costs, and benefits of mitigation and adaptation actions, including economic and non-economic metrics that evaluate the costs of action, inaction, and residual impacts. Focus is also needed on the development of methods and baseline information supporting evaluation of completed and ongoing adaptation, mitigation, and assessment efforts that will foster adaptive learning; and
• Develop, test, and expand integrated assessment models that link decisions about emissions with impacts under different development pathways and ways to categorize uncertainties in the supporting data.

Foundational Cross-Cutting Research Capabilities to Support Future Climate Assessments

This assessment identifies a set of five foundational cross-cutting research capabilities that are essential for advancing our ability to continue to conduct climate and global change assessments and for addressing the five research goals.

1. Integrate natural and social sciences, engineering, and other disciplinary approaches

Continued advances in comprehensive and useful climate assessments will rely on additional interdisciplinary research. Understanding of the coupled human-environment system is enriched by combining research from natural and social sciences with research and experience from the engineering, law, and business professions. Because human activities and decisions are influencing many Earth system processes, models and observations of natural and social changes at planetary, regional, and local scales are needed to understand how climate is changing, its impacts on people and environments, and how human responses feedback on the Earth system. Building experienced interdisciplinary research teams that are able to understand each other’s theories, methods, and language as well as the needs of stakeholders will allow for more rapid and effective assessments.

Interdisciplinary research is needed, for example, to:

• Understand how hydrological drivers of water supply interact with changing patterns of water demand and evolving water management practices to increase risks of drought, or influence the effectiveness of adaptation and mitigation options;
• Understand climate change in the context of multiple stresses on Earth, ecological, and human systems;
• Bring together economic and quantitative assessment of climate impacts and policies with other more qualitative assessments that include non-market and cultural values; and
• Integrate the understanding of human behavior, engineering, and genomics to expand the range of choice in responding to climate change by providing and thoroughly evaluating new options for adaption and mitigation that improve economic development, energy, health, and food security.

2. Ensure availability of observations, monitoring, and infrastructure for critical data collection and analysis

Our understanding and ability to assess changes in climate and other global processes is based on a comprehensive and sustained system of observations that document the history of climate, socioeconomic, and related changes at spatial and time scales relevant to global, regional, and sectoral needs. The most recent USGCRP Strategic Plan 5 states that to advance scientific knowledge of an integrated natural and human Earth system, an interoperable and integrated observational, monitoring, and data access capability is also essential. This observational capability is needed to gain the fundamental scientific understanding of essential status, trends, variability, and changes in the Earth system. It should include the physical, chemical, biological, and human components of the Earth system over multiple space and time scales.

To attain their full value, observational systems must provide data that are responsive to the needs of decision-makers in government, industry, and society. These needs include observations and data that can inform the nation’s strategies to respond to climate and global change, including, for example, efforts to limit emissions, monitor public health, capture and store carbon, monitor changes in ocean processes, and implement adaptation strategies. This will require establishing explicit baseline conditions, specifying spatial detail and temporal frequency of observations, including social data, and setting standards for metadata (information about collected data), interoperability, and regulatory and voluntary reporting, such as those outlined in the Informing an Effective Response to Climate Change Panel Report of the National Research Council’s Americas Climate Choices series. 6 These data need to be openly and widely available in order to support the best and most comprehensive science and for use in decision-making by a range of stakeholders.

This assessment shows that enhanced research and development will be necessary to ensure that the scope and integration of relevant scientific data improves overall utility for decision-makers, including better ways to communicate metadata, data quality, and uncertainties. The observations must include critical geophysical variables such as temperature, precipitation, sea level changes, ocean circulation, atmospheric composition, and hydrology; the essential parameters that describe the biosphere; and social science information on drivers, impacts, and responses to climate and other global changes. More comprehensive and integrated data capabilities are needed to document the processes and patterns that drive natural and social feedbacks and better describe the mechanisms of abrupt change. Progress is needed in particular for data-poor regions, focusing on inadequately documented socioeconomic, ecological, and health-related factors, and under-observed regional and sectoral data. There are opportunities to take advantage of citizen science observations where appropriate; monitor system resilience and robustness; and attend to physical and social systems that are not currently observed with sufficient temporal or spatial resolution to enable vulnerability analysis and decision support at regional and sectoral scales. More explicitly, strategic integration of our nation’s observations, monitoring, and data capabilities should be considered in order to:

• Sustain and integrate the nation’s capacity to observe long-term changes in the Earth system and improve fundamental understanding of the complex causes and consequences of global change, including integration of essential socioeconomic, health, and ecological observations;
• Maintain and enhance advanced modeling capability , including high-performance computing infrastructure, improvements in analysis of large and complex data sets, comprehensive Earth system and integrated assessment models, reanalysis, verification, and model comparisons;
• Better integrate observations and modeling to advance scientific understanding about past, present, and future climate within government, industry, and civil society; and
• Develop more fully the components and structure of a national climate and global change indicator system to support assessment that includes indicators of climate change, impacts, vulnerabilities, opportunities, and preparedness as well as trends and changes in land use, air and water pollution, water supply and demand, extreme events, diseases, public health, and agronomic data, coastal and ocean conditions (such as marine ecosystem health, ocean acidity, sea level, and salinity), cryosphere data (such as snow, sea ice conditions, ice sheets and glacier melt rates), and changes in public attitudes and understanding of climate change. All of these are important to assessing climate change, and should eventually be better coordinated at local, as well as national and regional levels in collaboration with local agencies.

3. Build capacity for climate assessment through training, education, and workforce development

Building human capacity for improved assessments requires expansion of skills within the existing public and private sectors and developing a much larger workforce that excels at critical and interdisciplinary thinking. Useful capacities include the ability to facilitate and communicate research and practice, manage collaborative processes to allow for imaginative analysis and solutions, develop sustainable technologies to reduce climate risks, and build tools for decision-making in an internationally interdependent world. A deeper understanding of the processes and impacts of climate change, disaster risk reduction, energy policy impacts, ecosystem services and biodiversity, poverty reduction, food security, and sustainable consumption requires new approaches to training and curriculum, as well as research to evaluate the effectiveness of different approaches to research and teaching.

Assessments will benefit from activities that:

• Strengthen approaches to education about climate, impacts, and responses including developing and evaluating the best ways to educate in the fields of science (natural and social), technology, engineering, and mathematics and related fields of study (such as business, law, medicine, and other relevant professional disciplines). Ideally, such training would include a deeper understanding of the climate system, natural resources, adaptation and energy policy options, and economic sustainability, and would build capacity at colleges and institutions, including minority institutions such as tribal colleges; and
• Identify increasingly effective approaches to developing a more climate-informed society that understands and can participate in assessments, including alternative media and methods for communication; this could also include a program to certify climate interpreters to actively assist decision-makers and policymakers to understand and use climate scenarios. 6

4. Enhance the development and use of scenarios

Scenarios are “coherent, internally consistent and plausible descriptions of possible future states of the world” 7 that provide reasoned projections of energy and land use, future population levels, economic activity, the structure of governance, social values, and patterns of technological change. They survey, integrate, and synthesize science, within and among scientific disciplines and across sectors and regions. Such scenarios are essential tools that enable projections of emissions, climate, vulnerabilities, and global change. They are indispensable for linking science and decision-making and for assessing choices about America’s climate future. Stakeholders and scientists within this assessment identified a need for more fully developed scenario-building capabilities that better enable assessments at regional and sectoral scales in timeframes of relevance to policy and decision-making and that more effectively reflect climate and global change at these scales.

Achieving capacity in scenario development will:

• Enhance understanding of how and why climate may change and its implications, especially at the regional scale. For example, a set of scenarios can be used to better understand the way energy, land use, and policy choices create alternative emissions pathways; how changes at global scales can be downscaled to estimate local climate possibilities; how various socioeconomic development pathways increase or decrease climate vulnerability; and to assess alternative strategies for reducing emissions and implementing adaptation; and
• Develop new methods, tools, and skills for applying scenarios to policy development at local levels in order to broaden society’s understanding of a changing climate and to analyze the full range of policy choices. In addition, improve capabilities in integrated assessment modeling to inform policy analysis and allow stakeholders to co-produce information and explore options for local and national decisions.

5. Promote international research and collaboration

Research efforts in support of climate assessment are very dependent on the international research community. International teams conduct Earth system monitoring and analysis using observing systems that cannot be funded and maintained by any one country alone. Many of the impacts of climate change in the U.S. are closely linked to how climate affects other parts of the world. There is general understanding that impacts of climate change on U.S. socioeconomic systems are mediated or amplified through globally connected commodity chains and prices; more detailed research on climate change and its impacts elsewhere is needed to provide accurate assessments of what could happen to U.S. regional and local economies. The U.S. has the capacity to leverage investments in collaborative international climate and global change scientific research efforts, examples of which include IGBP (International Geosphere-Biosphere Programme), WCRP (World Climate Research Programme), DIVERSITAS (an international program of biodiversity science), IHDP (International Human Dimensions Programme) (as they evolve into or in affiliation with the new Future Earth program), and IGFA (International Group of Funding Agencies for Global Change Research).

Supporting international collaborative research will:

• Contribute to international systems of data collection, monitoring, indicators, and modeling that closely track and project changes in Earth system dynamics, climate, human drivers, and climate impacts that are needed for national and international assessments;
• Assess the implications of climate change for globally shared common resources such as the oceans, polar regions, and migratory species; and
• Fill important gaps in understanding of how climate change in other countries affects U.S. food, energy, health, manufacturing, and national security.

Conclusions

This chapter summarizes research recommendations across a broad range of topics – research that the assessment authors deem essential to support future assessments. The authors recognize that federal agencies and others are making progress on many of these research areas and that sustained assessment is included in the goals of the USGCRP.

While the research goals discussed in this chapter are not ranked, the objectives listed below can be used as criteria for prioritizing these activities. The nation’s federal research investments in support of the sustained assessment strategy should be designed to enhance the nation’s ability to limit climate-related risk and increase the utility of scientific understanding in supporting decisions.

• Promote understanding of the fundamental behavior of the Earth’s climate and environmental systems: The consequences of climate variability and change will require enhanced investment in use-inspired research using both fundamental and applied analysis, providing a foundation for the nation’s sustained assessment process;
• Promote understanding of the socioeconomic impacts of a changing climate: Provide comprehensive understanding, including the development of indicators of the impacts and consequences of climate variability and change for regions and sectors within the United States;
• Build capacity to assess risks and consequences: Support improved, timely, and accessible estimations and projections of climate and other global change risks, their consequences and relevance for stakeholders, associated costs and benefits, and interactions with other stresses;
• Support research that enables infrastructure for analysis: Sustain and enhance critical infrastructure, including observations and data essential to monitoring trends, projecting climate risks, and evaluating the effectiveness of responses in decision-making and policy implementation;
• Build decision-support capacity: Build the knowledge base essential for decision support including developing and evaluating climate mitigation and adaptation solutions, technology innovation, institutions, and behavioral change; and
• Support engagement of the private sector and investment communities: Develop strategies to leverage federal research investments by engaging the private sector more fully in research and technology development, including partnerships with the nation’s universities and scientific research institutions, to address critical gaps in knowledge and to build the nation’s future scientific, technical, and sustained assessment capacities.
• Leverage private sector, university, and international resources and partnerships: Take advantage of topics and expertise where the U.S. can leverage and complement private sector and university capabilities, obtain return on research investments, and lead internationally on research investment efforts; build capacity through education and training; support humanitarian response; and fill critical gaps in global knowledge of relevance to the United States.

Bronen, R. , 2011: Climate-induced community relocations: Creating an adaptive governance framework based in human rights doctrine . New York University Review Law & Social Change , 35 , 357-408. URL | Detail ↩

, , 2007: Adaptation and mitigation options and responses, and the inter-relationship with sustainable development, at global and regional levels . Climate Change 2007: Synthesis Report. Contribution of Working Groups I, II and III to the Fourth Assessment Report of the Intergovernmental Panel on Climate Change , , Pachauri, R.K., and Reisinger, A., Eds. , IPCC, 56-62. URL | Detail ↩

, , 2007: Climate Change 2007: Impacts, Adaptation and Vulnerability. Contribution of Working Group II to the Fourth Assessment Report of the Intergovernmental Panel on Climate Change . Cambridge University Press, 976 pp. | Detail ↩

Karl, T. R., J. T. Melillo, and T. C. Peterson , 2009: Global Climate Change Impacts in the United States . T.R. Karl, Melillo, J.T., and Peterson, T.C., Eds. Cambridge University Press, 189 pp. URL | Detail ↩

, , 2010: Adapting to Impacts of Climate Change. America’s Climate Choices: Report of the Panel on Adapting to the Impacts of Climate Change . National Research Council. The National Academies Press, 292 pp. URL | Detail ↩

, , 2010: Informing an Effective Response to Climate Change. America’s Climate Choices: Panel on Informing Effective Decisions and Actions Related to Climate Change . National Research Council, Board on Atmospheric Sciences and Climate, Division on Earth and Life Studies, National Academies Press, 348 pp. URL | Detail ↩

, , 2010: Advancing the Science of Climate Change. America’s Climate Choices: Panel on Advancing the Science of Climate Change . National Research Council. The National Academies Press, 528 pp. URL | Detail ↩

, , 2010: Limiting the Magnitude of Future Climate Change. America’s Climate Choices. Panel on Limiting the Magnitude of Future Climate Change . National Research Council, Board on Atmospheric Sciences and Climate, Division of Earth and Life Studies. The National Academies Press, 276 pp. URL | Detail ↩

, , 2012: The National Global Change Research Plan 2012–2021: A Strategic Plan for the U.S. Global Change Research Program . 132 pp., The U.S. Global Change Research Program, Washington, D.C. URL | Detail ↩

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Original research article, full spectrum cannabidiol-rich extract reduced propofol dosage required for anesthetic induction in dogs—a pilot study.

• 1 Veterinary Medicine, Federal University of Santa Catarina (UFSC), Curitibanos, Brazil
• 2 Veterinary Clinic School (CVE) of the Federal University of Santa Catarina (UFSC), Curitibanos, Brazil
• 3 Department of Biosciences and One Health (BSU), Center for Rural Sciences (CCR), Federal University of Santa Catarina (UFSC), Curitibanos, Brazil
• 4 Cannabis Development and Innovation Center (PODICAN/UFSC), Curitibanos, Brazil

Introduction: Cannabinoids show great therapeutic potential, but their effect on anesthesia still remains unclear. Use of chronic recreational Cannabis in humans undergoing anesthetic procedures tends to require a higher dose when compared to non-users. On the other hand, studies on rodents and dogs have shown that cannabinoid agonists may potentiate certain anesthetics. This contrast of effects possibly occurs due to different time lengths of administration of different phytocannabinoids at different doses, and their distinct effects on the Endocannabinoid System, which is also affected by anesthetics such as propofol and isoflurane.

Methods: Twenty-seven healthy male dogs, client-owned, ranging from 1 to 7 years, and from 5 to 35 kg were selected, mean weight 15.03±7.39 kg, with owners volunteering their animals to participate in the research performed in the Federal University of Santa Catarina (UFSC). Dogs were randomized into 3 groups. The Control Group (CON, n = 9), receiving only Extra Virgin Olive Oil, the same oil-base used in the treatment groups. Group 2 (G2, n = 9) received 2 mg/kg of total phytocannabinoids, and Group 3 (G3, n = 9) received 6 mg/kg of total phytocannabinoids. All groups received their treatments transmucosally, 75 min before their induction with propofol. Heart and respiratory rate, blood pressure, temperature and sedation were evaluated prior to, and at 30, 60, and 75  min after administration of the fsCBD-rich extract or Placebo extract. Preanesthetic medication protocol was also included across all treatment groups, 15  min before induction. Parametric data was analyzed with one-way ANOVA, followed by Student–Newman–Keuls (SNK) if significant statistical differences were found. Non-parametric data was analyzed using Friedman’s test, followed by Dunn test for comparisons between all timepoints in the same group. Kruskal-Wallis followed by Dunn was utilized for between groups comparisons. Propofol dose necessary for induction was analyzed through One-way ANOVA followed by Tukey’s Multiple Comparisons Test, using Instat by Graphpad, and differences were considered statistically significant when p < 0.05. Our analysis assessed if statistical significance was present between time points in the same group, and between groups in the same time points.

Results: In our study, 6  mg/kg of total phytocannabinoids were able to reduce the dose of propofol necessary for induction by 23% when compared to the control group. The fsCBD-rich extract did not produce significant sedation within or between groups, although statistically significant differences in heart rate and systolic blood pressure were found.

Discussion: Our findings indicate that phytocannabinoids could be an adjunct option in anesthesia, although further research is necessary to better confirm this data. Additionally, further research is needed to determine the best dosage, delivery method, time for administration, ideal molecular profile for desired effects, safety, drug–drug interactions, and transurgical effects.

Introduction

Cannabis criminalization has made it challenging for scientists to study cannabis, limiting the scientific and medical communities’ understanding of its therapeutic potential. Modern principles of anesthesiology were established during cannabis prohibition and, for great part, under a complete unawareness of the endocannabinoid system and the role it may play in anesthesia. Therefore, the Endocannabinoid System (ECS) relation with anesthetics has not yet been deeply studied and remains unclear. There is, however, growing evidence that many commonly utilized pharmaceuticals interact with the ECS ( 1 – 7 ) and therefore many of their mechanisms may be, at least partially, mediated through this system.

Most modern research focused on the impact of chronic marijuana use on anesthetic induction In humans with chronic use of high doses of Tetrahydrocannabinol (THC), an exogenous agonist of the cannabinoid receptor 1 (CB1), a higher dose of propofol seems to be needed when compared to non-users ( 8 – 10 ), possibly due to a desensitization or downregulation of the receptor, which has been reported in rodents and humans chronically exposed to high levels of this molecule. In contrast, acute administrations of THC appear to increase the density of these receptors, and improve their sensitivity to endocannabinoids ( 4 ). Research done in mice has demonstrated that the administration of a synthetic cannabinoid agonist actually reduced propofol doses ( 1 ). This was also reported in dogs receiving phytocannabinoids intraperitoneally ( 11 ).

These different effects may be caused by different time lengths of administration of THC, although this awaits further research. Most likely, an increase in the receptor density and/or sensitivity improve propofol effects, since studies have indicated that propofol indirectly modulates CB1 ( 1 – 3 , 7 ).

The CB1 receptor is classified as a G-protein coupled receptor (GPCR) that interacts with ion channels in presynaptic neurons leading to its control on neurotransmission and pain modulation ( 12 , 13 ). One of the endogenous ligands of the CB1 receptor is the N-arachidonoylethanolamine or anandamide (AEA), transported intracellularly by Fatty Acid Binding Proteins (FABP) and later catabolized by the Fatty Acid Amide Hydrolase (FAAH) enzyme. Propofol appears to be a FAAH inhibitor ( 1 , 3 , 14 ), so by reducing the reuptake of anandamide, propofol allows a higher availability of this molecule. Cannabidiol (CBD), a phytocannabinoid, also inhibits this enzyme and binds to FABPs, reducing AEA breakdown and reuptake. Many of the effects of CBD are likely also mediated through these mechanisms of action ( 15 ). Besides enzymatic inhibition, CBD also acts as an allosteric modulator at this receptor, which can also be one of its mechanisms ( 16 ).

In this research, we evaluated the effects of different doses of phytocannabinoids administered transmucosally 60 min before anesthetic premedication in the propofol doses necessary for anesthetic induction.

Materials and methods

Full spectrum cannabidiol-rich extract and ethics board approval.

The Cannabis extracts (fsCBD-rich extract) used in this study were provided by the “Cannabis Sem Fronteiras” through their veterinary phytotherapy extension project (number 202213421). The oil consisted in a full spectrum cannabidiol-rich extract (fsCBD-rich) of CBD:THC ratio of approximately 21:1, and a CBD:CBDa ratio of 1.6:1 (Certificate of Analysis THCA22021606-01, The Higher Commitment Analytical Lab, United States) ( Table 1 ). The research was approved by the University Ethics Committee (number 2065211122), and the authorization to possess, transport and research Cannabis extracts was granted by means of the habeas corpus n° 5040089-27.2021.4.04.7200/SC.

Table 1 . fsCBD-rich extract composition.

Twenty-seven healthy male dogs, client-owned, ranging from 1 to 7 years, and from 5 to 35 kg were selected, mean weight 15.03 ± 7.39 kg, with owners volunteering their animals to participate in the research performed in the Federal University of Santa Catarina (UFSC). Dogs were randomized into 3 groups. The Control Group (CON, n  = 9), receiving only Extra Virgin Olive Oil, the same oil-base used in the treatment groups. Group 2 (G2, n  = 9) received 2 mg/kg of total phytocannabinoids, and Group 3 (G3, n  = 9) received 6 mg/kg of total phytocannabinoids. All groups received their treatments transmucosally, 75 min before their induction with propofol.

Inclusion and exclusion criteria

Upon arrival at the Veterinary Clinic School located at the Federal University of Santa Catarina - Curitibanos Campus, animals were physically examined and assessed for their level of activity and consciousness, mucosal color, capillary filling time, lymph node size, hydration, heart and respiratory rate, and rectal temperature by a veterinarian. Blood was drawn from each patient and sent to the Laboratory of Clinical Analysis of UFSC (LACLIN). Hematological and biochemical evaluation including complete blood count, leukogram, Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), urea, creatinine, albumin and total plasma protein levels. Animals that had slight elevations in albumin and total plasma protein which appeared clinically insignificant were not excluded. Animals that had any evidence of heart, liver, kidneys or metabolic disease in the blood work or physical examination were excluded from the study.

Randomization and blinding

Animals were randomly assigned to one of the three groups by the research coordinator through the randomizer.org website. Only the coordinator and the trained personnel administering the oil were aware of which treatment group each patient belonged to.

Clinical trial

Animals that met the criteria for inclusion were selected to participate in the research. Owners were requested not to provide food or water to the animals 12 h before the procedure. Upon arrival, hair was removed from the venous access region and in the region used to assess systolic blood pressure, and the patients were allowed to be accustomed to the dog kennels of University School Clinic (CVE/UFSC) for 10 min before their first evaluation.

Patients were evaluated in seven time points: immediately before the administration of the CBD-rich extracts (T1), 30 min after fsCBD-rich extract administration (T2), 60 min after fsCBD-rich extract administration (T3), 15 min after the administration of the preanesthetic medication (PM) (T4), at their venous access (T5), at their anesthetic induction (T6) and at their intubation (T7).

The fsCBD-rich extract and placebo were applied to patients’ gums by the same trained personnel immediately after the evaluations at T1, and in between evaluations, the animals were left alone in a quiet, slightly dark kennel.

Evaluations performed at T1, T2, T3, and T4 consisted of sedation level via the validated abbreviated Wagner scale ( 17 ), consisting in 4 evaluations: Spontaneous posture (E1), eyeball position (E2), noise reaction (E3), and attitude (E4). During all of these time points, vital parameters (VP) including heart rate (HR) and respiratory rate (RR), systolic blood pressure (SBP), and rectal temperature (RT) were also assessed by the same veterinarian. HR was assessed through auscultation with a stethoscope, RR was assessed through visual inspection, SPB was evaluated through a Parks Model 811-B Doppler, using cuffs of a size consistent with the animal being evaluated (40–50% of the circumference of the animal’s limb), and RT using a thermometer.

Immediately after the VP assessment at T3, PM was administered. It consisted of 0.05 mg/kg of acepromazine and 0.2 mg/kg of methadone administered intramuscularly, 60 min after the administration of the fsCBD-rich extract. After the evaluations at T4, animals were brought to the surgery center, in the next room, ready for their anesthetic induction. Venous access was obtained by placement and fixing of an intravenous catheter in the left thoracic limb, and its resistance evaluated through the scale adapted from Bortolami et al. ( 18 ), consisting of evaluation 5 at T5.

Immediately after, propofol was administered intravenously at a rate of 2 mg/kg/min through a Digicare syringe infusion pump, model SR31x. Administration stopped when the patient lost palpebral reflex and mandibular tone, allowing intubation, consisting in the Evaluation 6 (E6) at T6. Intubation was performed using an endotracheal tube of a compatible size, and its ease of placement was assessed using the modified scale of Lerche et al. ( 19 ), being the evaluation 7 (E7), performed at T7. Patient assessments scales are shown in Table 2 . Timepoints are summarized in Table 3 .

Table 2 . Patient assessments scales.

Table 3 . Timepoints evaluation summary.

Immediately after induction and intubation, the animals were coupled to the anesthetic system consistent with their size. Anesthetic maintenance was carried out through the administration of the volatile anesthetic Isoflurane dose-effect by a universal vaporizer, diluted in 100% O 2 . Patient vital signs were evaluated through pulse oximeter and rectal thermometer linked to a Deltalife multiparametric monitor, the respiratory rate was monitored by visualizing the patient’s chest movement, and his systolic blood pressure was measured using a Parks Model 811-B Doppler with a compatible cuff size, every 5 min or when necessary.

Patients were considered in the appropriate surgical anesthetic plane when they displayed no palpebral reflex, no mandibular tone and eye globes rotated rostrally. Hair was removed from the surgical site, and then prepared with aseptic technique with alcohol- iodine-alcohol, and local block performed with 2% lidocaine, at a dose of 5 mg/kg, applied to the spermatic cord. Subsequently, the open orchiectomy technique was performed by three surgeons throughout the project. At the end of the procedure, the isoflurane was turned off, and the patient was extubated when a swallowing reflex was present.

After the completion of the surgical procedure, patients were medicated subcutaneously with 0.2 mg/kg of Meloxicam, 5 mg/kg of Enrofloxacin and 25 mg/kg of dipyrone. After patient’s regained consciousness with a stable body temperature and normal coordination, medical release to the client was performed, with instructions for the use of an Elizabethan collar until the non-absorbable skin stitches were removed. The patients were prescribed Meloxicam 0.1 mg/kg for and Dipyrone 25 mg/kg, both orally, for 3 and 5 days, respectively.

Most patients returned after 10–15 days for suture removal or follow-up. A few owners decided to remove the sutures in private clinics for convenience, but reported back to the researchers indicating the animals were well, with no apparent complications from the surgical procedure. A few patients had suture dehiscence due to owners not being consistent with the use of the Elizabethan collar. Owners did not report any other major post-surgical complications.

Statistical analysis

Parametric data was analyzed with one-way ANOVA, followed by Student–Newman–Keuls (SNK) if significant statistical differences were found.

Non-parametric data was analyzed using Friedman’s test, followed by Dunn test for comparisons between all timepoints in the same group. Kruskal-Wallis followed by Dunn was utilized for between groups comparisons. Differences were considered statistically significant when p  < 0.05, and all these analyses were done using Instat by Graphpad.

Propofol dose necessary for induction was analyzed through One-way ANOVA followed by Tukey’s Multiple Comparisons Test, using Instat by Graphpad.

Our analysis assessed if statistical significance was present between time points in the same group, and between groups in the same time points. This way, we assessed if groups receiving fsCBD-rich extract showed any signs of sedation after administration, as well as if they appeared more sedated after the administration of the preanesthetic medication when compared to the control group.

Intraclass correlation coefficient was done comparing the results of both evaluators, assessing the reliability of the scale.

Sedation scale

The sedation chart for all groups can be found in Figure 1 . Although both evaluators were veterinarians, evaluator 2 is a postgraduate in anesthesiology, and is considered more experienced than Evaluator 1.

Figure 1 . Sedation score (sum of E1, E2, E3, and E4 of the abbreviated Wagner Scale) by timepoint for all groups: treated with control (CON), 2 mg/kg (G2) and 6 mg/kg (G3) of total phytocannabinoids, respectively, 75 min before anesthetic induction with propofol.

The G3 group, receiving 6 mg/kg of phytocannabinoids, required a significantly lower propofol dose ( p  < 0.0138) when compared to the placebo group (CON), by way of a one-way ANOVA followed by Tukey’s multiple comparisons test.

Statistical significance was found within all groups ( p value < 0.0001), when comparing E1, E2, E3 and E4 at T1, T2, T3 with T4 through one-way ANOVA and Student–Newman–Keuls (SNK) Multiple Comparisons Test. Comparisons involving only T1, T2, and T3, however, have not shown significant statistical difference, in all groups. Considering T4 was 15 min after the administration of the preanesthetic medication, sedation was expected for all patients.

Comparisons of the scores of E1, E2, E3, and E4 on T1, T2, and T3 among different groups have not shown significant statistical differences using one-way ANOVA analysis, for both evaluators. T2 had statistical difference utilizing this test, but SNK Multiple Comparisons Test demonstrated p value as 0.0936, considered not significant. Analysis of the total scores (sum of all evaluations performed on that timepoint) between groups have not demonstrated statistical significance.

These results indicate that administrations of 2 mg/Kg or 6 mg/Kg of phytocannabinoids in this fsCBD-rich extract did not have significant sedative effects on the patients, nor did they amplify the sedative effects of the combination of Acepromazine and Methadone.

Respiratory frequency

One-way ANOVA and SNK Multiple Comparisons tests have not demonstrated statistical difference in the respiratory frequency between evaluation time points, in all groups ( Figure 2 ).

Figure 2 . Mean values and standard deviation of the respiratory rate (RR, mov/min) of dogs underwenting elective orchiectomy, and treated with control (CON), 2 mg/kg (G2) and 6 mg/kg (G3) of total phytocannabinoids, respectively, 75 min before anesthetic induction with propofol.

Analysis through one-way ANOVA had statistical differences in CON and G3. SNK Multiple Comparisons test, however, has not shown statistical difference for CON but has confirmed the statistical significance in the heart rate between T1, T2, and T3 with T4 in the G3 ( Figure 3 ).

Figure 3 . Mean values and standard deviation of the heart rate (HR, beat/min) of dogs underwenting elective orchiectomy, and treated with control (CON), 2 mg/kg (G2) and 6 mg/kg (G3) of total phytocannabinoids, respectively, 75 min before anesthetic induction with propofol.

Systolic blood pressure

No statistical differences between evaluation time points in the CON. G2, however, had significant differences between T1, T2, T3 with T4. G3 had the same differences as G2, and also between T1 and T2, before the administration of the preanesthetic medication. All these statistical significant differences were confirmed through SNK Multiple Comparisons test ( Figure 4 ).

Figure 4 . Mean values and standard deviation of the systolic blood pressure (SBP, in mmHg) of dogs underwenting elective orchiectomy, and treated with control (CON), 2 mg/kg (G2) and 6 mg/kg (G3) of total phytocannabinoids, respectively, 75 min before anesthetic induction with propofol.

Temperature

Statistical differences were found in all groups, between T1, T2, T3 with T4. CON also had a significant difference between T1 and T3, and G2 had a significant difference between T1 and T2, and T1 and T3, confirmed through SNK Multiple Comparisons Test ( Figure 5 ).

Figure 5 . Mean values and standard deviation of the Rectal Temperature (RT, in °C) of dogs underwenting elective orchiectomy, and treated with control (CON), 2 mg/kg (G2) and 6 mg/kg (G3) of total phytocannabinoids, respectively, 75 min before anesthetic induction with propofol.

Mean values and standard deviation for all VP evaluated can be found in Table 4 .

Table 4 . Mean values and standard deviation of heart rate (HR, beat/min), respiratory rate (RR, mov/min), systolic blood pressure (SBP, in mmHg) and rectal temperature (TR in °C) of dogs underwent elective orchiectomy, and treated with placebo (CON), 2 mg/kg (G2) and 6 mg/kg (G3) of total phytocannabinoids, respectively, 75 min before anesthetic induction with propofol.

Resistance to catheter insertion

No statistical differences were found in analysis between groups through One-Way ANOVA.

Anesthetic induction

Analysis of the Propofol dosage required for induction showed a significant statistical difference among G3 and CON ( p  < 0.0138) using Tukey multiple comparison test. Analysis between G3 and G2, and between G2 and CON have not demonstrated significant statistical differences ( Figure 6 ).

Figure 6 . Mean values and standard deviation of the propofol dose required for anesthetic induction of dogs underwenting elective orchiectomy, and treated with control (CON), 2 mg/kg (G2) and 6 mg/kg (G3) of total phytocannabinoids, respectively, 75 min before anesthetic induction with propofol.

Ease of intubation

Means of the patients weights, propofol dose and volume, as well as medians of the scores of their resistance to catheter insertion and ease of intubation can be found in Table 5 .

Table 5 . Means of the patients weights, propofol dose and volume, and medians of the scores of their resistance to catheter insertion and ease of intubation.

Transsurgical parameters

During the surgery, patients were assessed using a pulse oximeter and rectal thermometer linked to a Deltalife multiparametric monitor (DL1000). Since anesthetic maintenance was done with Isoflurane dose-effect administered with an universal vaporizer under the supervision of an anesthesiologist, there was no standardization and measurement of the concentration utilized. Empirically, there was no evidence of any trans surgical problematic issues for any group.

The Cannabis plant has been utilized across various human cultures since ancient times, serving numerous purposes including medicine, fiber production, food, recreational use, and religious ceremonies ( 20 ). Veterinary literature reports the historical use of cannabis in animals dating back to at least the twelfth century ( 21 ), with early investigations focusing particularly on its effects in dogs ( 22 ). Despite extensive historical usage, gaps remain in our understanding of cannabis-derived molecules, particularly concerning their impact during anesthesia. Contemporary research has predominantly examined the anesthetic implications of marijuana consumption in humans, revealing altered propofol requirements in chronic users ( 8 – 10 ). Phytocannabinoids like THC and CBD exert a range of effects through diverse mechanisms ( 4 , 15 ), offering therapeutic potential across multiple medical domains. Furthermore, both propofol and CBD inhibit the enzyme FAAH ( 1 – 3 , 7 , 14 , 15 ), leading to increased levels of the endocannabinoid Anandamide, suggesting a shared pharmacological mechanism that may potentiate the effects of propofol through the endocannabinoid system.

In this study, a single-dose of 6 mg/kg of the fsCBD-rich extract produced a reduction of 23% on propofol dose necessary for induction in dogs. This finding agrees with other research that has shown that a Cannabis indica extract administered intraperitoneally in dogs reduced the propofol dosage for induction ( 11 ). Although authors have mentioned ropy saliva, this was not observed in the current study. Findings in rodents further confirm these results in which synthetic cannabinoid agonists reduced propofol dosage, while antagonists had the opposite effect ( 1 ).

Sedation scores comparison did not have significant statistical differences between groups, and between T1, T2 and T3, for both evaluators. These findings suggest that the administration of 2 mg/Kg or 6 mg/Kg of total phytocannabinoids from the fsCannabidiol-rich extract used in this study did not induce significant sedative effects on the patients, nor did they enhance the sedative effects of the combination of acepromazine and methadone.

CBD is not described as exercising sedative or psychoactive effects, with studies reporting doses ranging from 8 mg/kg ( 23 ) and up to 100 mg/kg ( 24 ) in dogs without major side effects. THC has been described as causing neurological side effects, such as hyperesthesia and proprioceptive deficit ( 25 ), as well as ataxia, lethargy, and hypothermia ( 26 ). These effects are described as temporary, more likely to appear when THC is in higher amounts and in first experience as patients seem to create a tolerance to these side effects when the dosage is incremented gradually over time. This molecule is a partial agonist of CB1 receptors located in the nervous system, and its short-term administration increases their expression, as well as improving the binding affinity of endocannabinoids therein ( 4 ).

THC was the third most concentrated molecule in the fsCBD-rich extract in a CBD:THC ratio of approximately 21:1. Although rare, side effects have been described for doses of THC of 0.1 mg/kg ( 26 ). In our study, G2 received 0.09 mg/kg and G3 received 0.28 mg/kg of THC, and our team has not seen any neurological side effects described by previous authors. The second most concentrated molecule in the extract used in this research was Cannabidiolic Acid (CBDa), present in a CBD:CBDa ratio of 1.6:1. Research in rodents demonstrates that CBDA appears to enhance CBD bioavailability by up to 14 times ( 27 ), and that its presence in the extract also improved bioavailability in dogs ( 28 , 29 ).

The presence of CBDa and THC may be responsible, at least partially, of the results we have described in our study. Both molecules might have altered the pharmacodynamic and/or pharmacokinetic of CBD, and THC might have increased CB1 receptor expression, potentiating propofol indirect action on it. Nevertheless, these are the authors hypothesis, and still await further research.

In the present study, the fsCBD-rich extract was administered to the patients’ gums. Oral and transmucosal administration have practically identical pharmacokinetics (PK), indicating that it is absorbed through the gastrointestinal tract in both routes of administration ( 28 ). Although there are discrepancies between the pharmacokinetics of CBD depending on its formulation and physiological factors, research indicates that its half-life is 4–8 h, and its plasma peak is reached within 2 h ( 23 , 28 ). A review published in 2023 has stated that Cannabis products have a large variability, and these results should be interpreted carefully ( 29 ). Nevertheless, the administration time of the extracts was calculated based on these PK studies, in which the administration of the PM and propofol coincided with the plasma peak of phytocannabinoids.

Sedation scores analysis have demonstrated statistical significance ( p value > 0.0001) when comparing T1, T2, and T3 with T4, for both evaluators. That was expected given that T4 occurred 15 min after administering preanesthetic medication, thus sedation was anticipated for all animals, considering that acepromazine and methadone can produce effective sedation when associated in adequate doses ( 30 ).

The Abbreviated Wagner Sedation scale was consistent in describing sedation for both evaluators after PM, as designed to. Despite our results not showing an enhanced sedation for the association of phytocannabinoids and PM, this could be a limitation of the Sedation scale that was utilized. Its parameters might not have been representative to evaluate the changes in animal’s behavior that the fsCBD-rich extracts produced, since anxiolytic effects have already been described ( 31 , 32 ).

G2 and G3 showed a statistically significant reduction in HR and SBP between T0, T1 and T2 with T3, and G3 also showed a reduction in SBP between T1 and T2, which did not occur in the CON. These variations in these parameters may have occurred due to the administration of the fsCBD-rich extract, suggesting possible anxiolytic effects. To better evaluate these results, it is likely that a specific scale for this type of analysis would be more appropriate.

These findings are corroborated by the literature, which indicates that Cannabis extracts can cause a decrease in HR and SBP in animals in stressful situations ( 31 – 34 ).

Other studies mention a modest change in heart rate variability and decreased heart rate after acute ingestion of CBD in humans, pointing out the inconsistency of this information across different studies. This data inconsistency can occur both due to individual factors and variations in product presentations ( 35 ). These changes in HR and SBP may be transient and occur quickly, and may not be observed in long-term studies depending on the time of assessment ( 33 ).

No statistically significant differences were observed in RR when comparing timepoints and groups. A systematic review mentions discrepant information on the hemodynamic effects of CBD, where it reduces RR in times of stress, but not under controlled conditions, in several species ( 34 ).

All groups showed a significant reduction in RT. Hypothermia is described as one of the side effects of delta-9-THC, especially at higher doses, while CBD has not been shown to cause changes in body temperature ( 26 ). The ECS is related to the maintenance of body temperature ( 36 ).

On the other hand, the area where patients were kept between assessments did not have thermal control, being necessary to use a portable heater to keep the environment warm as this research was done during the winter. This lack of precise temperature control may have been a significant factor in the reduction in RT identified in all groups participating in the research.

The analysis of HR, RR, SBP, and RT between groups, on the other hand, did not demonstrate a significant difference.

In conclusion, we have found that fs-CBD-rich Cannabis extracts have the potential of being an adjunct in anesthetic protocols, although this is a very initial finding. We strongly encourage other researchers to further investigate these results and its mechanisms, as understanding the interactions between the anesthetics, the Endocannabinoid System, and their interaction with phytocannabinoids, may allow discoveries in underlying mechanisms of different pharmaceuticals, and the development of new drugs or protocols that improves anesthetic procedures.

Limitations

Animals had different temperaments, with standardization not being ideal. Although this effect is minimized by the randomization and all of them were docile, this personality difference was evident throughout the research, as some animals were not accustomed to medical personal handling as the others. Animals also did not have a long period of time to be accustomed to the dog kennels, and only male dogs were included in this study.

The room which patients were kept between evaluations did not have controlled temperature. A portable heater had to be used in order to keep the patients warm during winter temperatures, and these different temperatures could be a factor in their behavior, and in the changes observed in heart rate, systolic blood pressure and temperature.

The Federal University of Santa Catarina lacks equipment to analyze how much volatile anesthetics are being used in each patient, with dose-effect being the standard procedure. Without knowing precisely how much volatile anesthetic was being used during the surgery, our research was unable to make any conclusions on the effects of the combination of Isoflurane and the fsCannabidiol-rich extract. The trans surgical parameters need to be better examined in future, better controlled studies.

Capnography parameters were not assessed among groups, as the Federal University of Santa Catarina does not have a calibrated vaporizer, capnography and gas analyzer available. With this being one of the main limitations of this research, and although all patients were well at the end of the procedures, we strongly advocate for other researchers to confirm all of the data here described, and further investigate the safety of the administration of full scale cannabidiol-rich extracts before general anesthesia through more robust, well controlled studies.

Data availability statement

The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.

Ethics statement

The animal studies were approved by the Animal Ethics Board of the Federal University of Santa Catarina (number 2065211122). The studies were conducted in accordance with the local legislation, institutional requirements and international ethical research guidelines. Written informed consent was obtained from the owners for the participation of their animals in this study.

Author contributions

JH: Conceptualization, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Resources, Supervision, Writing – original draft, Writing – review & editing. ME: Data curation, Project administration, Supervision, Writing – review & editing. LF: Project administration, Writing – review & editing. MN: Writing – original draft. JS: Writing – original draft. AD: Writing – original draft. EA: Conceptualization, Data curation, Investigation, Methodology, Project administration, Resources, Supervision, Writing – original draft, Writing – review & editing. VS: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Project administration, Supervision, Validation, Writing – original draft, Writing – review & editing.

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. JH received a masters degree fellowship from the National Coordination for the Improvement of Higher Education Personnel (CAPES). Project was funded with private resources from the team. Cannabis extracts were donated from “Cannabis Sem Fronteiras”.

Acknowledgments

Our deepest gratitude goes to Cannabis without borders, Vivian Dalla Colleta, Dr. Casara Andre, Dr. Kalinda Gupta, and Felipe Antônio Batistella for the help with this project.

Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Publisher’s note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

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Keywords: double blind, placebo controlled, prospective clinical study, cannabis, phytocannabinoid, anesthesia

Citation: Hasckel Gewehr JL, Enzele ML, Freiria LM, Nunes MM, Spengler J, Dondoerfer Teixeira AP, Amazonas E and Sasso Padilha V (2024) Full spectrum cannabidiol-rich extract reduced propofol dosage required for anesthetic induction in dogs—a pilot study. Front. Vet. Sci . 11:1352314. doi: 10.3389/fvets.2024.1352314

Received: 07 December 2023; Accepted: 12 March 2024; Published: 05 April 2024.

Reviewed by:

Copyright © 2024 Hasckel Gewehr, Enzele, Freiria, Nunes, Spengler, Dondoerfer Teixeira, Amazonas and Sasso Padilha. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: João Lourenço Hasckel Gewehr, [email protected]

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Kane RL, Guise JM, Hartman K, et al. Presentation of Future Research Needs [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2012 Apr. (Methods Future Research Needs Reports, No. 9.)

Presentation of Future Research Needs [Internet].

Introduction.

This methods paper was commissioned by the Agency for Healthcare Research and Quality (AHRQ) as one of a series of papers addressing methods issues in the relatively new area of explicit discussion of future research needs (FRN) as part of comparative effectiveness research (CER). This paper is intended to reflect current and recommended practices for the AHRQ Evidence-based Practice Centers (EPC), but these methods will certainly be refined in the coming years through both the EPC program and related initiatives as envisioned by the Affordable Care Act. Other papers in this methods series on future research needs in comparative effectiveness research may be found on AHRQ’s effective health care (EHC) Web site: www.effectivehealthcare.ahrq.gov/futureresearchneedsmethods.cfm .

• Comparative Effectiveness Research

CER is the “generation and synthesis of evidence that compares the benefits and harms of alternative methods to prevent, diagnose, treat, and monitor a clinical condition or to improve delivery of care. The purpose of CER is to assist consumers, clinicians, purchasers, and policymakers to make informed decisions that will improve care both at the individual and the population levels.” 1 CER comprises a broad range of activities and types of study, encompassing systematic reviews, secondary data analyses, randomized controlled trials, prospective observational studies, health systems research, and dissemination of results to the public, providers, policymakers, and other key stakeholders. Key components of CER include comparisons between active treatments, policies, or diagnostic strategies with evidence from research conducted in settings similar to those in which most patients with a given condition are treated. The explicit nature of CER is demonstrated by the descriptions of proposed study questions through the PICOTS formalism, in which each Key Question is described using six dimensions: Population; Intervention; Comparator treatment or test; Outcomes assessed; Timeframe; Study setting. 2

• Future Research Needs

Systematic reviews of focused clinical and policy questions reach conclusions whenever feasible and describe the strength of evidence supporting those conclusions. However, many reviews find only low or moderate strength of evidence to address a given Key Question. Problems are often identified with the amount or quality of the literature examined, leading to an inability to address all of the components of the key study questions to sufficiently address the clinical and policy needs that led to the Key Questions. Gaps in the evidence remain. A common criticism of systematic reviews is that, while they generally contain a section describing the limitations of the research just reviewed, these limitations sections often are very general (e.g., “larger trials are needed”) and provide relatively little guidance to funders or the research community regarding the next study or series of studies needed to advance a given field. 3 Yet a key, and to date, underutilized role of the systematic review process is to stimulate new research to address identified gaps in the literature.

With these FRN papers and accompanying methods papers, the AHRQ EPC Program distinguishes between the evidence gaps that are identified from within a systematic review and those that are prioritized and clearly defined as research needs by stakeholders based on their potential impact on practice or care. A more explicit and prioritized listing of research needs, with guidance regarding how to address those needs, could allow the impact of systematic reviews to be more fully realized and increase the pace of research to provide meaningful answers. The audience for future research needs reports includes the research community, funders, policymakers, and advocacy groups. Reducing the time between synthesis of evidence, identification of future research needs, and initiation of studies to address those needs is urgently needed in the current health care environment.

The Future Research Needs Process

In the AHRQ EHC program, FRN documents are derived from systematic reviews of CER questions. The FRN document follows online publication of the systematic review and serves as a standalone document. Figure 1 shows the flow of an FRN project.

Flowchart of future research needs process. * May include identification of additional evidence gaps. † Reduction through topic consolidation, preliminary prioritization, and consideration of ongoing research (duplication criteria).

Each FRN report begins with identifying a list of evidence gaps from the systematic review (in draft or final form), which may be augmented with input from a multidisciplinary panel of stakeholders familiar with both the research methods and the clinical and policy content of the systematic review. The EPC then works with the stakeholder group to elaborate and consolidate the evidence gaps, taking into consideration any ongoing or planned research that may already be addressing gaps. Potential research questions are then elaborated following the PICOTS framework with the exception of methodological questions, which may be organized differently. 4 Once the questions have been formalized, they are given a final ranking by the stakeholders according to potential value criteria. The final list of 4–12 high priority Future Research Needs with specific questions, including PICOTS definition (as appropriate) and potential study designs, is published in a final document intended for use by researchers and funders of research.

Scope of This Paper

This paper is one of a series of papers that provide recommendations and best practices on the steps in identifying and prioritizing Future Research Needs. (This particular paper addresses issues around presenting the findings from an FRN analysis, which are covered in steps 4, 6, and 7. This paper does not address other related issues around determining research gaps, orienting stakeholders to CER questions, FRN process and prioritization criteria, elaboration of evidence gaps, and ranking research needs, within steps 1, 2, 3, and 5, which are covered in related papers. 5 – 7 ) Other papers that address other steps in the FRN process will be posted as they are completed at www.effectivehealthcare.ahrq.gov/futureresearchneedsmethods.cfm .

• Background and Rationale

The goal of the FRN documents is to encourage further research based on the shortcomings identified in the comparative effectiveness (CE) reviews, by extending the discussion raised in those reports. We walk a fine line between stimulating action and appearing overly prescriptive. The question of the “desirable” level of detail in laying out future research needs is related to larger questions of:

• Who is the primary audience for the reports (funding agencies, researchers)?
• Is the prioritization activity a technical exercise in which solutions (highly specified research studies to address research needs) are found? or
• Are stakeholders engaged in a prioritization activity that leads to insights and broad understanding of research needs?

These questions may also be related to the extent of the evidence base in the underlying field of research. It is possible that fields with a large evidence base are more amenable to focused prioritization efforts that yield highly specified research questions.

Stakeholder perspective offers some clues about which approach (technical or broader insights) may be the most appropriate. In some cases, stakeholders may move the identification to a broader plane than was originally anticipated. For example, the future research needs report on weight gain in pregnancy offered the following narrative: “Stakeholders were reluctant to dictate a specific form of study design because they felt that many of the research areas were at a nascent stage that might benefit from a multiplicity of approaches. In addition, while the group was inspired to map the identified research priorities to study approaches, they were reluctant to specify a single, correct next step. They expressed confidence in the collective energy and creativity of the scientific community, suggesting that agencies and organizations seeking to advance research in this area solicit and amply fund investigator-initiated research rather than prespecifying study designs to answer high priority questions. Likewise there was confidence that robust expertise and appropriate study populations are available to realize answers to the prioritized questions quickly in order to bring practical tools and new knowledge to advancing the care of women and their children.” 8

Stakeholder reactions varied for other topics. For example, members of the stakeholder panel on treatment for localized prostate cancer 9 took into account two large, lengthy randomized controlled trials that were then underway and sought to identify potential studies and research designs that could enrich the evidence base while awaiting the results of those trials. They also shifted the emphasis from specific treatments to determining which patients should be treated and when, because of their concern about substantial overtreatment in this patient population.

In addition to the pilot work in FRN documents, recognizing that this was a new area of work, these eight centers were also engaged in methodological development to provide an underpinning for eventual programmatic guidance. One of these projects was devoted to defining an optimal format for presenting research needs. 10

As a result of these early experiences in piloting approaches to FRN development and prioritization, and exploration of methods, AHRQ has identified the need for program guidance on a structured and consistent method for presenting FRNs. Initial efforts have been made to create guidance, but initial experience has suggested that further refinements are indicated.

This project explores how recommendations for FRNs beyond the work done in CE reviews can be best organized and presented across a variety of topics. It delineates the elements and presentation that are most helpful in a standalone future research needs document.

In the context of the FRN document, this relates specifically to the way the prioritized list of research needs (the “future research needs”) are presented. Early experience suggests two categories of research gaps, one related to the topic area and another related to methodological issues. This report will inform presentation elements and the level of detail that are appropriate for each.

• Cite this Page Kane RL, Guise JM, Hartman K, et al. Presentation of Future Research Needs [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2012 Apr. (Methods Future Research Needs Reports, No. 9.) Introduction.
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