scholarly journals Neuromodulation for Pain: A Comprehensive Survey and Systematic Review of Clinical Trials and Connectomic Analysis of Brain Targets

2021 ◽  
pp. 1-12
Author(s):  
Kazuaki Yamamoto ◽  
Gavin J.B. Elias ◽  
Michelle E. Beyn ◽  
Ajmal Zemmar ◽  
Aaron Loh ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Clinical Trials ◽  
Pain Relief ◽  
Brain Stimulation ◽  
Health Care Systems ◽  
Network Connectivity ◽  
Mapping Analysis ◽  
Care Systems ◽  
Comprehensive Survey ◽  
Clinical Trials Registry

<b><i>Background:</i></b> Chronic pain is a debilitating condition that imposes a tremendous burden on health-care systems around the world. While frontline treatments for chronic pain involve pharmacological and psychological approaches, neuromodulation can be considered for treatment-resistant cases. Neuromodulatory approaches for pain are diverse in both modality and target and their mechanism of action is incompletely understood. <b><i>Objectives:</i></b> The objectives of this study were to (i) understand the current landscape of pain neuromodulation research through a comprehensive survey of past and current registered clinical trials (ii) investigate the network underpinnings of these neuromodulatory treatments by performing a connectomic mapping analysis of cortical and subcortical brain targets that have been stimulated for pain relief. <b><i>Methods:</i></b> A search for clinical trials involving pain neuromodulation was conducted using 2 major trial databases (ClinicalTrials.gov and the International Clinical Trials Registry Platform). Trials were categorized by variables and analyzed to gain an overview of the contemporary research landscape. Additionally, a connectomic mapping analysis was performed to investigate the network connectivity patterns of analgesic brain stimulation targets using a normative connectome based on a functional magnetic resonance imaging dataset. <b><i>Results:</i></b> In total, 487 relevant clinical trials were identified. Noninvasive cortical stimulation and spinal cord stimulation trials represented 49.3 and 43.7% of this count, respectively, while deep brain stimulation trials accounted for &#x3c;3%. The mapping analysis revealed that superficial target connectomics overlapped with deep target connectomics, suggesting a common pain network across the targets. <b><i>Conclusions:</i></b> Research for pain neuromodulation is a rapidly growing field. Our connectomic network analysis reinforced existing knowledge of the pain matrix, identifying both well-described hubs and more obscure structures. Further studies are needed to decode the circuits underlying pain relief and determine the most effective targets for neuromodulatory treatment.

scholarly journals Computer-Aided Pharmacoepidemiology in Drug Use and Safety: Examining the Intersection between Data Science and Medicines Research

2021 ◽  
Author(s):  
Ibrahim Chikowe ◽  
Elias Peter Mwakilama
Keyword(s):  
Health Care ◽  
Clinical Trials ◽  
Research Agenda ◽  
Data Science ◽  
Health Care Systems ◽  
Computer Aided ◽  
Care Systems ◽  
Research Narrative ◽  
Randomised Controlled ◽  
Improving Health Care

Pharmacoepidemiology is a relatively new area of study that focuses on research aimed at producing data about drugs’ usage and safety in well-defined populations. Its significant impact on patient safety has translated into improving health care systems worldwide, where it has been widely adopted. This field has developed to an extent that policy and guidelines makers have started using its evidence alongside that produced from randomised controlled clinical trials. Although this significant improvement has been partly attributed to the adoption of statistics and computer-aided models into the way pharmacoepidemiology studies are designed and conducted, certain gaps still exist. This chapter reports some of the significant developments made, along with the gaps observed so far, in the adoption of statistics and computing into pharmacoepidemiology research. The goal is to highlight efforts that have led to the new pharmacoepidemiology developments, while examining the intersection between data science and pharmacology through research narrative reviews of computer-aided pharmacology. The chapter shows the significant number of initiatives that have been applied/adopted to improve pharmacoepidemiology research. Nonetheless, further developments in integrating pharmacoepidemiology with computers and statistics are needed in order to enhance the research agenda.

Eye on China

2019 ◽  
Vol 23 (10) ◽  
pp. 6-9
Keyword(s):  
Artificial Intelligence ◽  
Chronic Pain ◽  
Clinical Trials ◽  
Pain Relief ◽  
Dengue Virus ◽  
Ovarian Tissue ◽  
African Swine Fever ◽  
Pharmacy Services ◽  
Chinese Scientist ◽  
Novel Drug

The following topics are under this section: 50 young scientists awarded with the inaugural XPLORER PRIZE Chinese scientist find new possibilities in dengue virus control Optimizing microbial microenvironment for development of novel Biophotovoltaics System Novel drug for chronic pain relief enter clinical trials China taps into artificial intelligence to improve pharmacy services Patient in China who received world’s first pig cornea regains eyesight China sees its first childbirth through cryopreservation of ovarian tissue China toughens crackdown on illegal African swine fever vaccines

scholarly journals Clinical Strategies for the Treatment and Management of Patients Prescribed Long-term Opioid Therapy

Pain Medicine ◽  
2018 ◽  
Vol 20 (9) ◽  
pp. 1737-1744
Author(s):  
Jessica J Wyse ◽  
Linda Ganzini ◽  
Steven K Dobscha ◽  
Erin E Krebs ◽  
Janet Zamudio ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Drug Testing ◽  
Health Care Systems ◽  
Qualitative Interviews ◽  
The United States ◽  
Opioid Therapy ◽  
Prescribing Practices ◽  
Policy And Practice ◽  
Care Systems

Abstract Objectives Across diverse health care systems, growing recognition of the harms associated with long-term opioid therapy (LTOT) for chronic pain has catalyzed substantial changes to policy and practice designed to promote safer prescribing and patient care. Although clear goals have been defined, how clinics and providers should most effectively implement these changes has been less well defined, and facilities and providers have had substantial flexibility to innovate. Methods Qualitative interviews were conducted with 24 Department of Veterans Affairs (VA) clinicians across the United States who prescribe LTOT for chronic pain. Interviews probed the practices and initiatives providers utilized to meet opioid safety requirements and address common challenges in caring for patients prescribed LTOT. Results Innovative strategies in the design and organization of clinical practice (urine drug testing, informed consent, limiting transfer requests, specialty patient panel) and resources utilized (engaged pharmacists, non-opioid pain treatments, intra-organizational collaborations) are described. Conclusions We conclude with recommendations designed to improve opioid prescribing practices, both within the VA and in other settings.

scholarly journals Potential Anti-SARS-CoV-2 Therapeutics That Target the Post-Entry Stages of the Viral Life Cycle: A Comprehensive Review

Viruses ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 1092
Author(s):  
Rami A. Al-Horani ◽  
Srabani Kar
Keyword(s):  
Clinical Trials ◽  
Life Cycle ◽  
Clinical Investigation ◽  
Early Stage ◽  
Health Care Systems ◽  
Viral Life Cycle ◽  
Chemical Structures ◽  
Care Systems ◽  
Post Entry ◽  
Potential Therapeutics

The coronavirus disease-2019 (COVID-19) pandemic continues to challenge health care systems around the world. Scientists and pharmaceutical companies have promptly responded by advancing potential therapeutics into clinical trials at an exponential rate. Initial encouraging results have been realized using remdesivir and dexamethasone. Yet, the research continues so as to identify better clinically relevant therapeutics that act either as prophylactics to prevent the infection or as treatments to limit the severity of COVID-19 and substantially decrease the mortality rate. Previously, we reviewed the potential therapeutics in clinical trials that block the early stage of the viral life cycle. In this review, we summarize potential anti-COVID-19 therapeutics that block/inhibit the post-entry stages of the viral life cycle. The review presents not only the chemical structures and mechanisms of the potential therapeutics under clinical investigation, i.e., listed in clinicaltrials.gov, but it also describes the relevant results of clinical trials. Their anti-inflammatory/immune-modulatory effects are also described. The reviewed therapeutics include small molecules, polypeptides, and monoclonal antibodies. At the molecular level, the therapeutics target viral proteins or processes that facilitate the post-entry stages of the viral infection. Frequent targets are the viral RNA-dependent RNA polymerase (RdRp) and the viral proteases such as papain-like protease (PLpro) and main protease (Mpro). Overall, we aim at presenting up-to-date details of anti-COVID-19 therapeutics so as to catalyze their potential effective use in fighting the pandemic.

scholarly journals Medical cannabis or cannabinoids for chronic non-cancer and cancer related pain: a systematic review and meta-analysis of randomised clinical trials

BMJ ◽  
2021 ◽  
pp. n1034 ◽  
Author(s):  
Li Wang ◽  
Patrick J Hong ◽  
Curtis May ◽  
Yasir Rehman ◽  
Yvgeniy Oparin ◽  
...  
Keyword(s):  
Systematic Review ◽  
Chronic Pain ◽  
Clinical Trials ◽  
Pain Relief ◽  
Physical Functioning ◽  
Meta Analysis ◽  
Medical Cannabis ◽  
Increased Risk ◽  
Small Improvement

Abstract Objective To determine the benefits and harms of medical cannabis and cannabinoids for chronic pain. Design Systematic review and meta-analysis. Data sources MEDLINE, EMBASE, AMED, PsycInfo, CENTRAL, CINAHL, PubMed, Web of Science, Cannabis-Med, Epistemonikos, and trial registries up to January 2021. Study selection Randomised clinical trials of medical cannabis or cannabinoids versus any non-cannabis control for chronic pain at ≥1 month follow-up. Data extraction and synthesis Paired reviewers independently assessed risk of bias and extracted data. We performed random-effects models meta-analyses and used GRADE to assess the certainty of evidence. Results A total of 32 trials with 5174 adult patients were included, 29 of which compared medical cannabis or cannabinoids with placebo. Medical cannabis was administered orally (n=30) or topically (n=2). Clinical populations included chronic non-cancer pain (n=28) and cancer related pain (n=4). Length of follow-up ranged from 1 to 5.5 months. Compared with placebo, non-inhaled medical cannabis probably results in a small increase in the proportion of patients experiencing at least the minimally important difference (MID) of 1 cm (on a 10 cm visual analogue scale (VAS)) in pain relief (modelled risk difference (RD) of 10% (95% confidence interval 5% to 15%), based on a weighted mean difference (WMD) of −0.50 cm (95% CI −0.75 to −0.25 cm, moderate certainty)). Medical cannabis taken orally results in a very small improvement in physical functioning (4% modelled RD (0.1% to 8%) for achieving at least the MID of 10 points on the 100-point SF-36 physical functioning scale, WMD of 1.67 points (0.03 to 3.31, high certainty)), and a small improvement in sleep quality (6% modelled RD (2% to 9%) for achieving at least the MID of 1 cm on a 10 cm VAS, WMD of −0.35 cm (−0.55 to −0.14 cm, high certainty)). Medical cannabis taken orally does not improve emotional, role, or social functioning (high certainty). Moderate certainty evidence shows that medical cannabis taken orally probably results in a small increased risk of transient cognitive impairment (RD 2% (0.1% to 6%)), vomiting (RD 3% (0.4% to 6%)), drowsiness (RD 5% (2% to 8%)), impaired attention (RD 3% (1% to 8%)), and nausea (RD 5% (2% to 8%)), but not diarrhoea; while high certainty evidence shows greater increased risk of dizziness (RD 9% (5% to 14%)) for trials with <3 months follow-up versus RD 28% (18% to 43%) for trials with ≥3 months follow-up; interaction test P=0.003; moderate credibility of subgroup effect). Conclusions Moderate to high certainty evidence shows that non-inhaled medical cannabis or cannabinoids results in a small to very small improvement in pain relief, physical functioning, and sleep quality among patients with chronic pain, along with several transient adverse side effects, compared with placebo. The accompanying BMJ Rapid Recommendation provides contextualised guidance based on this body of evidence. Systematic review registration https://osf.io/3pwn2

scholarly journals Potential Anti-COVID-19 Therapeutics that Block the Early Stage of the Viral Life Cycle: Structures, Mechanisms, and Clinical Trials

2020 ◽  
Vol 21 (15) ◽  
pp. 5224 ◽  
Author(s):  
Rami A. Al-Horani ◽  
Srabani Kar ◽  
Kholoud F. Aliter
Keyword(s):  
Clinical Trials ◽  
Life Cycle ◽  
Early Stage ◽  
Health Care Systems ◽  
Viral Life Cycle ◽  
Sulfated Polysaccharides ◽  
Angiotensin Converting Enzyme 2 ◽  
Care Systems ◽  
Cycle Structures ◽  
Potential Therapeutics

The ongoing pandemic of coronavirus disease-2019 (COVID-19) is being caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The disease continues to present significant challenges to the health care systems around the world. This is primarily because of the lack of vaccines to protect against the infection and the lack of highly effective therapeutics to prevent and/or treat the illness. Nevertheless, researchers have swiftly responded to the pandemic by advancing old and new potential therapeutics into clinical trials. In this review, we summarize potential anti-COVID-19 therapeutics that block the early stage of the viral life cycle. The review presents the structures, mechanisms, and reported results of clinical trials of potential therapeutics that have been listed in clinicaltrials.gov. Given the fact that some of these therapeutics are multi-acting molecules, other relevant mechanisms will also be described. The reviewed therapeutics include small molecules and macromolecules of sulfated polysaccharides, polypeptides, and monoclonal antibodies. The potential therapeutics target viral and/or host proteins or processes that facilitate the early stage of the viral infection. Frequent targets are the viral spike protein, the host angiotensin converting enzyme 2, the host transmembrane protease serine 2, and clathrin-mediated endocytosis process. Overall, the review aims at presenting update-to-date details, so as to enhance awareness of potential therapeutics, and thus, to catalyze their appropriate use in combating the pandemic.

scholarly journals Functional MRI Signature of Chronic Pain Relief From Deep Brain Stimulation in Parkinson Disease Patients

Neurosurgery ◽  
2019 ◽  
Vol 85 (6) ◽  
pp. E1043-E1049 ◽  
Author(s):  
Marisa DiMarzio ◽  
Tanweer Rashid ◽  
Ileana Hancu ◽  
Eric Fiveland ◽  
Julia Prusik ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Deep Brain Stimulation ◽  
Pain Relief ◽  
Parkinson Disease ◽  
Anterior Cingulate Cortex ◽  
Functional Mri ◽  
Brain Stimulation ◽  
Cingulate Cortex ◽  
Anterior Cingulate ◽  
Deep Brain

Abstract BACKGROUND Chronic pain occurs in 83% of Parkinson disease (PD) patients and deep brain stimulation (DBS) has shown to result in pain relief in a subset of patients, though the mechanism is unclear. OBJECTIVE To compare functional magnetic resonance imaging (MRI) data in PD patients with chronic pain without DBS, those whose pain was relieved (PR) with DBS and those whose pain was not relieved (PNR) with DBS. METHODS Functional MRI (fMRI) with blood oxygen level-dependent activation data was obtained in 15 patients in control, PR, and PNR patients. fMRI was obtained in the presence and absence of a mechanical stimuli with DBS ON and DBS OFF. Voxel-wise analysis using pain OFF data was used to determine which regions were altered during pain ON periods. RESULTS At the time of MRI, pain was scored a 5.4 ± 1.2 out of 10 in the control, 4.25 ± 1.18 in PNR, and 0.8 ± 0.67 in PR cohorts. Group analysis of control and PNR groups showed primary somatosensory (SI) deactivation, whereas PR patients showed thalamic deactivation and SI activation. DBS resulted in more decreased activity in PR than PNR (P < .05) and more activity in anterior cingulate cortex (ACC) in PNR patients (P < .05). CONCLUSION Patients in the control and PNR groups showed SI deactivation at baseline in contrast to the PR patients who showed SI activation. With DBS ON, the PR cohort had less activity in SI, whereas the PNR had more anterior cingulate cortex activity. We provide pilot data that patients whose pain responds to DBS may have a different fMRI signature than those who do not, and PR and PNR cohorts produced different brain responses when DBS is employed.

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