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World Neurosurgery Mar 2022Optimal outcomes after large-vessel occlusion (LVO) stroke are highly dependent on prompt diagnosis, effective communication, and treatment, making LVO an attractive... (Review)
Review
BACKGROUND
Optimal outcomes after large-vessel occlusion (LVO) stroke are highly dependent on prompt diagnosis, effective communication, and treatment, making LVO an attractive avenue for the application of artificial intelligence (AI), specifically machine learning (ML). Our objective is to conduct a systematic review to describe existing AI applications for LVO strokes, delineate its effectiveness, and identify areas for future AI applications in stroke treatment and prognostication.
METHODS
A systematic review was conducted by searching the PubMed, Embase, and Scopus databases. After deduplication, studies were screened by title and abstract. Full-text studies were screened for final inclusion based on prespecified inclusion and exclusion criteria. Relevant data were extracted from each study.
RESULTS
Of 11,512 resultant articles, 40 were included. Of 30 studies with reported ML algorithms, the most commonly used ML algorithms were convolutional neural networks in 10 (33.3%), support vector machines in 10 (33.0%), and random forests in 9 (30.0%). Studies examining triage favored direct transport to a stroke center and predicted improved outcomes. ML techniques proved vastly accurate in identifying LVO on computed tomography. Applications of AI to patient selection for thrombectomy are lacking, although some studies determine individual patient eligibility for endovascular treatment with high accuracy. ML algorithms have reasonable accuracy in predicting clinical and angiographic outcomes and associated factors.
CONCLUSIONS
AI has shown promise in the diagnosis and triage of patients with acute stroke. However, the role of AI in the management and prognostication remains limited and warrants further research to help in decision support.
Topics: Arterial Occlusive Diseases; Artificial Intelligence; Brain Ischemia; Humans; Ischemic Stroke; Stroke; Thrombectomy; Triage
PubMed: 34896351
DOI: 10.1016/j.wneu.2021.12.004 -
Neuropsychology Review Jun 2023Deep brain stimulation (DBS) of the subthalamic nucleus (STN) or globus pallidum internus (GPi) improves motor functions in patients with Parkinson's disease (PD) but... (Meta-Analysis)
Meta-Analysis Review
Deep brain stimulation (DBS) of the subthalamic nucleus (STN) or globus pallidum internus (GPi) improves motor functions in patients with Parkinson's disease (PD) but may cause a decline in specific cognitive domains. The aim of this systematic review and meta-analysis was to assess the long-term (1-3 years) effects of STN or GPi DBS on four cognitive functions: (i) memory (delayed recall, working memory, immediate recall), (ii) executive functions including inhibition control (Color-Word Stroop test) and flexibility (phonemic verbal fluency), (iii) language (semantic verbal fluency), and (iv) mood (anxiety and depression). Medline and Web of Science were searched, and studies published before July 2021 investigating long-term changes in PD patients following DBS were included. Random-effects model meta-analyses were performed using the R software to estimate the standardized mean difference (SMD) computed as Hedges' g with 95% CI. 2522 publications were identified, 48 of which satisfied the inclusion criteria. Fourteen meta-analyses were performed including 2039 adults with a clinical diagnosis of PD undergoing DBS surgery and 271 PD controls. Our findings add new information to the existing literature by demonstrating that, at a long follow-up interval (1-3 years), both positive effects, such as a mild improvement in anxiety and depression (STN, Hedges' g = 0,34, p = 0,02), and negative effects, such as a decrease of long-term memory (Hedges' g = -0,40, p = 0,02), verbal fluency such as phonemic fluency (Hedges' g = -0,56, p < 0,0001), and specific subdomains of executive functions such as Color-Word Stroop test (Hedges' g = -0,45, p = 0,003) were observed. The level of evidence as qualified with GRADE varied from low for the pre- verses post-analysis to medium when compared to a control group.
Topics: Adult; Humans; Parkinson Disease; Deep Brain Stimulation; Subthalamic Nucleus; Globus Pallidus; Cognition; Neuropsychological Tests
PubMed: 35318587
DOI: 10.1007/s11065-022-09540-9 -
Cancer Treatment Reviews Dec 2022Metastatic triple-negative breast cancer (mTNBC) is a poor prognostic disease with limited treatments and uncertain therapeutic algorithms. We performed a systematic... (Review)
Review
Metastatic triple-negative breast cancer (mTNBC) is a poor prognostic disease with limited treatments and uncertain therapeutic algorithms. We performed a systematic review and multiple Bayesian network meta-analyses according to treatment line to establish an optimal therapeutic sequencing strategy for this lethal disease. We included 125 first-line trials (37,812 patients) and 33 s/further-lines trials (11,321 patients). The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall response rates (ORR), overall survival (OS) and safety, for first and further lines, separately. We also estimated separate treatment rankings for the first and subsequent lines according to each endpoint, based on (surface under the cumulative ranking curve) SUCRA values. No first-line treatment was associated with superior PFS and OS than paclitaxel ± bevacizumab. Platinum-based polychemotherapies were generally superior in terms of ORR, at the cost of higher toxicity.. PARP-inhibitors in germline-BRCA1/2-mutant patients, and immunotherapy + chemotherapy in PD-L1-positive mTNBC, performed similar to paclitaxel ± bevacizumab. In PD-L1-positive mTNBC, pembrolizumab + chemotherapy was better than atezolizumab + nab-paclitaxel in terms of OS according to SUCRA values. In second/further-lines, sacituzumab govitecan outperformed all other treatments on all endpoints, followed by PARP-inhibitors in germline-BRCA1/2-mutant tumors. Trastuzumab deruxtecan in HER2-low mTNBC performed similarly and was the best advanced-line treatment in terms of PFS and OS after sacituzumab govitecan, according to SUCRA values. Moreover, comparisons with sacituzumab govitecan, talazoparib and olaparib were not statistically significant. The most effective alternatives or candidates for subsequent lines were represented by nab-paclitaxel (in ORR), capecitabine (in PFS) and eribulin (in PFS and OS).
Topics: Humans; Triple Negative Breast Neoplasms; Bevacizumab; Poly(ADP-ribose) Polymerase Inhibitors; Network Meta-Analysis; B7-H1 Antigen; Antineoplastic Combined Chemotherapy Protocols; Bayes Theorem; Paclitaxel; Algorithms
PubMed: 36202026
DOI: 10.1016/j.ctrv.2022.102468 -
BMC Psychiatry Feb 2018There is increasing recognition of the therapeutic function pets can play in relation to mental health. However, there has been no systematic review of the evidence... (Review)
Review
BACKGROUND
There is increasing recognition of the therapeutic function pets can play in relation to mental health. However, there has been no systematic review of the evidence related to the comprehensive role of companion animals and how pets might contribute to the work associated with managing a long-term mental health condition. The aim of this study was to explore the extent, nature and quality of the evidence implicating the role and utility of pet ownership for people living with a mental health condition.
METHODS
A systematic search for studies exploring the role of companion animals in the management of mental health conditions was undertaken by searching 9 databases and undertaking a scoping review of grey literature from the earliest record until March 2017. To be eligible for inclusion, studies had to be published in English and report on primary data related to the relationship between domestic animal ownership and the management of diagnosable mental health conditions. Synthesis of qualitative and quantitative data was undertaken in parallel using a narrative synthesis informed by an illness work theoretical framework.
RESULTS
A total of 17 studies were included in the review. Quantitative evidence relating to the benefits of pet ownership was mixed with included studies demonstrating positive, negative and neutral impacts of pet ownership. Qualitative studies illuminated the intensiveness of connectivity people with companion animals reported, and the multi-faceted ways in which pets contributed to the work associated with managing a mental health condition, particularly in times of crisis. The negative aspects of pet ownership were also highlighted, including the practical and emotional burden of pet ownership and the psychological impact that losing a pet has.
CONCLUSION
This review suggests that pets provide benefits to those with mental health conditions. Further research is required to test the nature and extent of this relationship, incorporating outcomes that cover the range of roles and types of support pets confer in relation to mental health and the means by which these can be incorporated into the mainstay of support for people experiencing a mental health problem.
Topics: Animals; Emotions; Human-Animal Bond; Humans; Mental Disorders; Mental Health; Narration; Pets; Qualitative Research
PubMed: 29402247
DOI: 10.1186/s12888-018-1613-2 -
Fertility and Sterility Jan 2021Can the priorities for future research in infertility be identified?
STUDY QUESTION
Can the priorities for future research in infertility be identified?
SUMMARY ANSWER
The top 10 research priorities for the four areas of male infertility, female and unexplained infertility, medically assisted reproduction, and ethics, access, and organization of care for people with fertility problems were identified.
WHAT IS KNOWN ALREADY
Many fundamental questions regarding the prevention, management, and consequences of infertility remain unanswered. This is a barrier to improving the care received by those people with fertility problems.
STUDY DESIGN, SIZE, DURATION
Potential research questions were collated from an initial international survey, a systematic review of clinical practice guidelines, and Cochrane systematic reviews. A rationalized list of confirmed research uncertainties was prioritized in an interim international survey. Prioritized research uncertainties were discussed during a consensus development meeting. Using a formal consensus development method, the modified nominal group technique, diverse stakeholders identified the top 10 research priorities for each of the categories male infertility, female and unexplained infertility, medically assisted reproduction, and ethics, access, and organization of care.
PARTICIPANTS/MATERIALS, SETTING, METHODS
Healthcare professionals, people with fertility problems, and others (healthcare funders, healthcare providers, healthcare regulators, research funding bodies and researchers) were brought together in an open and transparent process using formal consensus methods advocated by the James Lind Alliance.
MAIN RESULTS AND THE ROLE OF CHANCE
The initial survey was completed by 388 participants from 40 countries, and 423 potential research questions were submitted. Fourteen clinical practice guidelines and 162 Cochrane systematic reviews identified a further 236 potential research questions. A rationalized list of 231 confirmed research uncertainties were entered into an interim prioritization survey completed by 317 respondents from 43 countries. The top 10 research priorities for each of the four categories male infertility, female and unexplained infertility (including age-related infertility, ovarian cysts, uterine cavity abnormalities, and tubal factor infertility), medically assisted reproduction (including ovarian stimulation, IUI, and IVF), and ethics, access, and organization of care, were identified during a consensus development meeting involving 41 participants from 11 countries. These research priorities were diverse and seek answers to questions regarding prevention, treatment, and the longer-term impact of infertility. They highlight the importance of pursuing research which has often been overlooked, including addressing the emotional and psychological impact of infertility, improving access to fertility treatment, particularly in lower resource settings, and securing appropriate regulation. Addressing these priorities will require diverse research methodologies, including laboratory-based science, qualitative and quantitative research, and population science.
LIMITATIONS, REASONS FOR CAUTION
We used consensus development methods, which have inherent limitations, including the representativeness of the participant sample, methodological decisions informed by professional judgement, and arbitrary consensus definitions.
WIDER IMPLICATIONS OF THE FINDINGS
We anticipate that identified research priorities, developed to specifically highlight the most pressing clinical needs as perceived by healthcare professionals, people with fertility problems, and others, will help research funding organizations and researchers to develop their future research agenda.
STUDY FUNDING/ COMPETING INTEREST(S)
The study was funded by the Auckland Medical Research Foundation, Catalyst Fund, Royal Society of New Zealand, and Maurice and Phyllis Paykel Trust. Geoffrey Adamson reports research sponsorship from Abbott, personal fees from Abbott and LabCorp, a financial interest in Advanced Reproductive Care, committee membership of the FIGO Committee on Reproductive Medicine, International Committee for Monitoring Assisted Reproductive Technologies, International Federation of Fertility Societies, and World Endometriosis Research Foundation, and research sponsorship of the International Committee for Monitoring Assisted Reproductive Technologies from Abbott and Ferring. Siladitya Bhattacharya reports being the Editor-in-Chief of Human Reproduction Open and editor for the Cochrane Gynaecology and Fertility Group. Hans Evers reports being the Editor Emeritus of Human Reproduction. Andrew Horne reports research sponsorship from the Chief Scientist's Office, Ferring, Medical Research Council, National Institute for Health Research, and Wellbeing of Women and consultancy fees from Abbvie, Ferring, Nordic Pharma, and Roche Diagnostics. M. Louise Hull reports grants from Merck, grants from Myovant, grants from Bayer, outside the submitted work and ownership in Embrace Fertility, a private fertility company. Neil Johnson reports research sponsorship from Abb-Vie and Myovant Sciences and consultancy fees from Guerbet, Myovant Sciences, Roche Diagnostics, and Vifor Pharma. José Knijnenburg reports research sponsorship from Ferring and Theramex. Richard Legro reports consultancy fees from Abbvie, Bayer, Ferring, Fractyl, Insud Pharma and Kindex and research sponsorship from Guerbet and Hass Avocado Board. Ben Mol reports consultancy fees from Guerbet, iGenomix, Merck, Merck KGaA and ObsEva. Ernest Ng reports research sponsorship from Merck. Craig Niederberger reports being the Co Editor-in-Chief of Fertility and Sterility and Section Editor of the Journal of Urology, research sponsorship from Ferring, and retains a financial interest in NexHand. Jane Stewart reports being employed by a National Health Service fertility clinic, consultancy fees from Merck for educational events, sponsorship to attend a fertility conference from Ferring, and being a clinical subeditor of Human Fertility. Annika Strandell reports consultancy fees from Guerbet. Jack Wilkinson reports being a statistical editor for the Cochrane Gynaecology and Fertility Group. Andy Vail reports that he is a Statistical Editor of the Cochrane Gynaecology & Fertility Review Group and of the journal Reproduction. His employing institution has received payment from HFEA for his advice on review of research evidence to inform their 'traffic light' system for infertility treatment 'add-ons'. Lan Vuong reports consultancy and conference fees from Ferring, Merck and Merck Sharp and Dohme. The remaining authors declare no competing interests in relation to the present work. All authors have completed the disclosure form.
TRIAL REGISTRATION NUMBER
Not applicable.
Topics: Consensus; Delphi Technique; Female; Fertility Clinics; Humans; Infertility; International Cooperation; Male; Practice Guidelines as Topic; Pregnancy; Reproductive Medicine; Research
PubMed: 33272617
DOI: 10.1016/j.fertnstert.2020.11.014 -
Osteoarthritis and Cartilage Open Jun 2023Genicular artery embolization (GAE) is a novel, minimally invasive procedure for treatment of knee osteoarthritis (OA). This meta-analysis investigated the safety and... (Review)
Review
OBJECTIVE
Genicular artery embolization (GAE) is a novel, minimally invasive procedure for treatment of knee osteoarthritis (OA). This meta-analysis investigated the safety and effectiveness of this procedure.
DESIGN
Outcomes of this systematic review with meta-analysis were technical success, knee pain visual analog scale (VAS; 0-100 scale), WOMAC Total Score (0-100 scale), retreatment rate, and adverse events. Continuous outcomes were calculated as the weighted mean difference (WMD) versus baseline. Minimal clinically important difference (MCID) and substantial clinical benefit (SCB) rates were estimated in Monte Carlo simulations. Rates of total knee replacement and repeat GAE were calculated using life-table methods.
RESULTS
In 10 groups (9 studies; 270 patients; 339 knees), GAE technical success was 99.7%. Over 12 months, the WMD ranged from -34 to -39 at each follow-up for VAS score and -28 to -34 for WOMAC Total score (all p < 0.001). At 12 months, 78% met the MCID for VAS score; 92% met the MCID for WOMAC Total score, and 78% met the SCB for WOMAC Total score. Higher baseline knee pain severity was associated with greater improvements in knee pain. Over 2 years, 5.2% of patients underwent total knee replacement and 8.3% received repeat GAE. Adverse events were minor, with transient skin discoloration as the most common (11.6%).
CONCLUSIONS
Limited evidence suggests that GAE is a safe procedure that confers improvement in knee OA symptoms at established MCID thresholds. Patients with greater knee pain severity may be more responsive to GAE.
PubMed: 36865988
DOI: 10.1016/j.ocarto.2023.100342 -
Expert Review of Neurotherapeutics Jan 2020: The American Psychiatric Association included Internet gaming disorder (IGD) in the 5th Edition of the Diagnostic and Statistical Manual of Mental Disorders, and the...
: The American Psychiatric Association included Internet gaming disorder (IGD) in the 5th Edition of the Diagnostic and Statistical Manual of Mental Disorders, and the World Health Organization included gaming disorder in the 11th revision of the International Classification of Diseases. These recent updates suggest significant concern related to the harms of excessive gaming.: This systematic review provides an updated summary of the scientific literature on treatments for IGD. Inclusion criteria were that studies: 1) evaluate the effectiveness of an intervention for IGD or excessive gaming; 2) use an experimental design (i.e. multi-armed [randomized or nonrandomized] or pretest-posttest); 3) include at least 10 participants per group; and 4) include an outcome measure of IGD symptoms or gaming duration. The review identified 22 studies evaluating treatments for IGD: 8 evaluating medication, 7 evaluating cognitive behavioral psychotherapy, and 7 evaluating other interventions and psychosocial treatments.: Even with the recent uptick in publication of such clinical trials, methodological flaws prevent strong conclusions about the efficacy of any treatment for IGD. Additional well-designed clinical trials using common metrics for assessing IGD symptoms are needed to advance the field.
Topics: Cognitive Behavioral Therapy; Humans; Internet Addiction Disorder; Psychosocial Intervention; Video Games
PubMed: 31544539
DOI: 10.1080/14737175.2020.1671824 -
Expert Opinion on Drug Metabolism &... May 2020: Pregnancy-related physiological changes exert a crucial impact on the pharmacokinetics of antidepressants; however, the current evidence presents inconsistencies. A... (Meta-Analysis)
Meta-Analysis
: Pregnancy-related physiological changes exert a crucial impact on the pharmacokinetics of antidepressants; however, the current evidence presents inconsistencies. A clearer understanding of pregnancy-related effects on antidepressant disposition may facilitate the development of guidelines for appropriate dose adjustments during the course of pregnancy based on therapeutic drug monitoring.: We systematically reviewed studies comparing antidepressant levels in the same individuals during pregnant and non-pregnant states. Using dose-adjusted plasma concentration measurements, we estimated alteration ratios between the 3rd trimester and baseline (before or after pregnancy). Additionally, we performed a meta-analysis for changes in dose-adjusted concentrations to estimate mean differences.: Data for several antidepressants display clear alteration patterns during pregnancy. On the basis of the alteration ratios trimipramine, fluvoxamine, and nortriptyline show a prominent decrease in dose-adjusted levels, especially in the 3rd trimester. Clomipramine, imipramine, citalopram, and paroxetine show smaller decreases in dose-adjusted concentrations in the third trimester. For escitalopram, venlafaxine and fluoxetine, changes are considered negligible. For sertraline, there was a tendency toward increased dose-adjusted concentrations in pregnancy. Available evidence suffers from major limitations and factors affecting pharmacokinetics have been insufficiently addressed. Further research is required to promote knowledge on pregnancy effects on antidepressant pharmacokinetics.
Topics: Antidepressive Agents; Depression; Dose-Response Relationship, Drug; Female; Humans; Pregnancy; Pregnancy Complications; Pregnancy Trimester, Third
PubMed: 32238008
DOI: 10.1080/17425255.2020.1750598 -
PloS One 2021To review the effect of different intramuscular injection (IMI) techniques on injection associated pain, in adults. (Meta-Analysis)
Meta-Analysis
AIM
To review the effect of different intramuscular injection (IMI) techniques on injection associated pain, in adults.
METHODS
The review protocol was registered on PROSPERO (CRD42019136097). MEDLINE, EMBASE, British Nursing Index and CINAHL were searched up to June 2020. Included studies were appraised and a meta-analysis, where appropriate, was conducted with a random effects model and test for heterogeneity. Standardised mean difference (SMD) with a 95% confidence interval in reported injection pain (intervention cf. control) was reported.
RESULTS
29 studies were included in the systematic review and 20 studies in the meta-analysis. 13 IMI techniques were identified. 10 studies applied local pressure to the injection site. Of these, applying manual pressure (4 studies, SMD = -0.85[-1.36,-0.33]) and Helfer (rhythmic) tapping (3 studies, SMD = -2.95[-5.51,-0.39]) to the injection site reduced injection pain, whereas the use of a plastic device to apply local pressure to the skin (ShotBlocker) did not significantly reduce pain (2 studies, SMD = -0.51[-1.58,0.56]). Acupressure techniques which mostly involved applying sustained pressure followed by intermittent pressure (tapping) to acupressure points local to the injection site reduced pain (4 studies: SMD = -1.62[-2.80,-0.44]), as did injections to the ventrogluteal site compared to the dorsogluteal site (2 studies, SMD = -0.43[-0.81,-0.06]). There was insufficient evidence on the benefits of the 'Z track technique' (2 studies, SMD = -0.20[-0.41,0.01]) and the cold needle technique (2 studies, SMD = -0.73[-1.83,0.37]) on injection pain. The effect of changing the needle after drawing up the injectate on injection pain was conflicting and warming the injectate did not reduce pain. Limitations included considerable heterogeneity, poor reporting of randomisation, and possible bias in outcome measures from unblinding of assessors or participants.
CONCLUSIONS
Manual pressure or rhythmic tapping over the injection site and applying local pressure around the injection site reduced IMI pain. However, there was very high unexplained heterogeneity between studies and risk of significant bias within small studies.
Topics: Humans; Injections, Intramuscular; Pain; Pain Measurement
PubMed: 33939726
DOI: 10.1371/journal.pone.0250883 -
Clinical Orthopaedics and Related... Mar 2020Blood flow restriction (BFR) is a process of using inflatable cuffs to create vascular occlusion within a limb during exercise. The technique can stimulate muscle...
BACKGROUND
Blood flow restriction (BFR) is a process of using inflatable cuffs to create vascular occlusion within a limb during exercise. The technique can stimulate muscle hypertrophy and improve physical function; however, most of these studies have enrolled healthy, young men with a focus on athletic performance. Furthermore, much of the information on BFR comes from studies with small samples sizes, limited follow-up time, and varied research designs resulting in greater design, selection, and sampling bias. Despite these limitations, BFR's popularity is increasing as a clinical rehabilitation tool for aging patients. It is important for practitioners to have a clear understanding of the reported effects of BFR specifically in older adults while simultaneously critically evaluating the available literature before deciding to employ the technique.
QUESTIONS/PURPOSES
(1) Does BFR induce skeletal muscle hypertrophy in adults older than 50 years of age? (2) Does BFR improve muscle strength and/or physical function in adults older than 50 years?
METHODS
Using PubMed, Google Scholar, Web of Science, and Science Direct, we conducted a systematic review of articles using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to assess the reported effects of BFR on skeletal muscle in older adults. Included articles enrolled participants 50 years of age or older and used BFR in conjunction with exercise to study the effects of BFR on musculoskeletal outcomes and functionality. The following search terms were used: "blood flow restriction" OR "KAATSU" OR "ischemic training" AND "clinical" AND "elderly." After duplicates were removed, 1574 articles were reviewed for eligibility, and 30 articles were retained with interventions duration ranging from cross-sectional to 16 weeks. Sample sizes ranged from 6 to 56 participants, and exercise tasks included passive mobilization or electrical stimulation; walking; resistance training using machines, free weights, body weight, or elastic bands; and water-based activities. Furthermore, healthy participants and those with cardiovascular disease, osteoarthritis, osteoporosis, sporadic inclusion body myositis, spinal cord injuries, and current coma patients were studied. Lastly, retained articles were assigned a risk of bias score using aspects of the Risk of Bias in Nonrandomized Studies of Interventions and the Cochrane Collaboration's tool for assessing the risk of bias in randomized trials.
RESULTS
BFR, in combination with a variety of exercises, was found to result in muscle hypertrophy as measured by muscle cross-sectional area, thickness, volume, mass, or circumference. Effect sizes for BFR's ability to induce muscle hypertrophy were calculated for 16 of the 30 papers and averaged 0.75. BFR was also shown to improve muscle strength and functional performance. Effect sizes were calculated for 21 of the 30 papers averaging 1.15.
CONCLUSIONS
Available evidence suggests BFR may demonstrate utility in aiding rehabilitation efforts in adults older than 50 years of age, especially for inducing muscle hypertrophy, combating muscle atrophy, increasing muscle strength, and improving muscle function. However, most studies in this systematic review were at moderate or high risk of bias; that being so, the findings in this systematic review should be confirmed, ideally using greater sample sizes, randomization of participants, and extended follow-up durations.
LEVEL OF EVIDENCE
Level II, systematic review.
Topics: Aged; Exercise Therapy; Female; Humans; Hypertrophy; Male; Middle Aged; Muscle Strength; Muscle, Skeletal; Orthopedic Procedures; Regional Blood Flow; Vasoconstriction
PubMed: 31860546
DOI: 10.1097/CORR.0000000000001090